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Qiao R, Zhou X, Li W, Zhong R, Wang J, Song Y, Zhang J, Xu T, Wang Y, Dai L, Gu W, Han B, Yang R. The association between blood-based HYAL2 methylation and early-stage lung cancer: a case-control study. Lung Cancer Manag 2025; 14:2477411. [PMID: 40168159 PMCID: PMC11970770 DOI: 10.1080/17581966.2025.2477411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 02/27/2025] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND Blood-based DNA methylation biomarkers have great potential for the early detection of lung cancer (LC). Here, we investigated the association between HYAL2 methylation in peripheral blood and LC. METHODS Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was performed to measure the methylation levels of 4 CpG sites in HYAL2 gene in two independent case-control studies (168 LC cases and 167 controls in Study I, 677 LC cases and 833 controls in Study II). Logistic regression adjusted for covariates was conducted for odds ratios (ORs) and 95% confidence intervals (CIs). Non-parametric tests were applied for the comparisons of stratified groups. RESULTS Hypomethylation of all 4 CpG sites in HYAL2 was associated with early-stage LC in the two studies (ORs range from 1.91 to 3.07 in Study I, ORs range from 1.39 to 1.86 in Study II, p < 0.05 for all). The associations were still significant for the very early-stage LC patients (stage I). Subgroup analysis indicated that the associations could be enhanced by male gender and older age. Moreover, decreased HYAL2 methylation was correlated with increased tumor size, tumor length and stage. CONCLUSIONS Our results suggested blood-based HYAL2 hypomethylation as a potential biomarker for LC early detection.
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Affiliation(s)
- Rong Qiao
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Xiajie Zhou
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- Nanjing Medical University Affiliated Nanjing Center for Disease Control and Prevention, Nanjing, China
| | - Wenli Li
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Runbo Zhong
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Jun Wang
- Research and Development, Nanjing TANTICA Biotechnology Co. Ltd, Nanjing, China
| | - Yakang Song
- Research and Development, Nanjing TANTICA Biotechnology Co. Ltd, Nanjing, China
| | - Jing Zhang
- Research and Development, Nanjing TANTICA Biotechnology Co. Ltd, Nanjing, China
| | - Tian Xu
- Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Yue Wang
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Liping Dai
- Henan Institute of Medical and Pharmaceutical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, China
| | - Wanjian Gu
- Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Baohui Han
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Rongxi Yang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- Research and Development, Nanjing TANTICA Biotechnology Co. Ltd, Nanjing, China
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Xu H, Fu X, Wang S, Ge Y, Zhang L, Li J, Zhang F, Yang Y, He Y, Sun Y, Gao A. Immunoglobulin-like transcript 5 polarizes M2-like tumor-associated macrophages for immunosuppression in non-small cell lung cancer. Int J Cancer 2025; 156:2225-2236. [PMID: 39910654 PMCID: PMC11970544 DOI: 10.1002/ijc.35360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 11/28/2024] [Accepted: 12/04/2024] [Indexed: 02/07/2025]
Abstract
Immune checkpoint inhibitors (ICIs) have shifted the treatment paradigm of non-small cell lung cancer (NSCLC) over the last decade. Despite notable therapeutic advancements in responders, the response rate remains limited owing to the immunosuppressive tumor microenvironment (TME). Therefore, to improve the efficacy of ICIs, it is essential to explore alternative targets or signals that mediate immunosuppression. Immunoglobulin-like transcript (ILT) 5 is a negative regulator of immune activation in myeloid cells. However, the expression and function of ILT5 in NSCLC remain unknown. Here, we found that ILT5 was highly expressed in tumor-associated macrophages (TAMs) of NSCLC tissues and predicted poor patient survival. Functionally, ILT5 induces the M2-like polarization of TAMs, which subsequently decreases the density of T cells, and increases FOXP3+T cell accumulation, leading to an immunosuppressive TME. The combination of ILT5 expression with M2-like TAM density is a more reliable biomarker of patient survival than ILT5 expression alone. ILT5 knockout mitigates the reprogramming of TAM and T cell subsets toward immunosuppressive phenotypes and inhibits tumor growth in vivo. These findings highlight that ILT5 is a potential immunotherapeutic target and a promising prognostic biomarker for NSCLC.
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Affiliation(s)
- Huijun Xu
- Jinan Central HospitalShandong UniversityJinanShandongChina
- Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina
| | - Xuebing Fu
- Department of Thoracic Radiation Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
| | - Shuyun Wang
- Phase I Clinical Research Center, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
| | - Yihui Ge
- Phase I Clinical Research Center, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
| | - Lu Zhang
- Department of OncologyThe Fourth People's Hospital of ZiboZiboShandongChina
| | - Juan Li
- Phase I Clinical Research Center, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
| | - Fang Zhang
- Department of OncologyCentral Hospital affiliated to Shandong First Medical UniversityJinanShandongChina
| | - Yang Yang
- Department of Ultrasound, The First Affiliated Hospital of USTC, Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina
| | - Yifu He
- Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina
| | - Yuping Sun
- Phase I Clinical Research Center, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
| | - Aiqin Gao
- Department of Thoracic Radiation Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
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Cai S, Yang W, Xing H, Yang J, Luo H, Ye X. Bibliometric analysis of current trends and emerging patterns in the application of nanomaterials for non-small cell lung cancer. Discov Oncol 2025; 16:802. [PMID: 40382731 PMCID: PMC12086128 DOI: 10.1007/s12672-025-02602-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Accepted: 05/06/2025] [Indexed: 05/20/2025] Open
Abstract
BACKGROUND Lung cancer is one of the most prevalent tumor diagnoses and a leading cause of cancer-related mortality worldwide. Among its two primary subtypes, non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancer cases. Over the past decade, a significant number of publications have explored the application of nanomaterials in NSCLC. This study aimed to comprehensively evaluate the current state and evolving trends in research focused on utilizing nanomaterials as potent diagnostic and therapeutic tools for NSCLC. METHODS To identify all pertinent publications, we used the Web of Science Core Collection (WoSCC) database. Based on stringent inclusion and exclusion criteria, relevant publications were carefully selected. For the bibliometric and visual analyses, we employed VOSviewer (version 1.6.20), CiteSpace (version 6.1.6), and R-bibliometrix (version 4.3.2). RESULTS Our analysis encompassed 1880 studies that fulfilled the inclusion criteria. We observed a steady increase in annual publications from 2014 to June 22, 2024. China, the USA, and India have emerged as leading nations in this field. Notably, the Chinese Academy of Sciences and Wang J stood out as the most influential institutions and authors, respectively. Most publications are featured in The International Journal of Nanomedicine. The keywords used in these publications were closely tied to non-small cell lung cancer and nanomaterials. In the past three years, "green synthesis" exhibited the highest burst strength, while "immune response" and "nanocrystal" represented emerging areas of intense research interest. CONCLUSION Through our exhaustive analysis, we synthesized the current research trends and emerging landscapes of nanomaterials in NSCLC. We characterized the publication patterns, pinpointed the most influential nations, institutions, authors, journals, and hot topics related to nanomaterial applications in NSCLC, and proposed potential avenues for future development.
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Affiliation(s)
- Shanshan Cai
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1 Minde Road, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Weichang Yang
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1 Minde Road, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Hongquan Xing
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1 Minde Road, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Jiale Yang
- Hepatobiliary and Pancreatic Surgery Division, Department of General Surgery, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330038, China
| | - Hongdan Luo
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1 Minde Road, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Xiaoqun Ye
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1 Minde Road, Nanchang, 330006, Jiangxi, People's Republic of China.
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Maurya N, Meena A, Luqman S. Role of microRNAs in lung oncogenesis: Diagnostic implications, resistance mechanisms, and therapeutic strategies. Int J Biol Macromol 2025:144261. [PMID: 40381781 DOI: 10.1016/j.ijbiomac.2025.144261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 04/16/2025] [Accepted: 05/14/2025] [Indexed: 05/20/2025]
Abstract
Lung cancer continues to pose a significant global health concern, presenting a formidable challenge on a worldwide scale, necessitating a deeper understanding of molecular mechanisms underlying its pathogenesis and treatment responses. microRNA (miRNA) modulation in the context of lung cancer therapeutics aims to unravel the complexities of miRNA-mediated regulatory networks. This comprehensive review elucidates microRNA's diverse roles in lung cancer, encompassing their involvement in key signaling pathways, cellular processes, the regulation of oncogenic or tumor-suppressive targets, and drug sensitivity. Moreover, this review critically examines the potential of miRNAs as diagnostic and prognostic biomarkers and their implications in therapeutic interventions for lung cancer. microRNAs are effective in making lung cancer therapy more efficient. They can make tumor cells more responsive to chemotherapy, radiation, and targeted therapies. microRNAs can target the drug efflux mechanism, increasing the effectiveness of chemotherapy agents and decreasing resistance. Furthermore, microRNAs play a crucial role in developing and inhibiting the resistance mechanisms against conventional treatments; improving the dysregulated expression of microRNAs enhances the therapeutic efficacy of existing therapies. By compiling knowledge on miRNA-mediated processes related to lung cancer, this review offers a comprehensive resource for researchers to understand and address the complexities of oncogenesis, diagnostics, resistance mechanisms, and therapeutic strategies.
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Affiliation(s)
- Nidhi Maurya
- CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226 015, Uttar Pradesh, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 001, Uttar Pradesh, India
| | - Abha Meena
- CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226 015, Uttar Pradesh, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 001, Uttar Pradesh, India
| | - Suaib Luqman
- CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226 015, Uttar Pradesh, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 001, Uttar Pradesh, India.
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5
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Shin JW, Nguyen TM, Jee SH. Association Between Creatinine and Lung Cancer Risk in Men Smokers: A Comparative Analysis with Antioxidant Biomarkers from the KCPS-II Cohort. Antioxidants (Basel) 2025; 14:584. [PMID: 40427466 PMCID: PMC12108704 DOI: 10.3390/antiox14050584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2025] [Revised: 05/08/2025] [Accepted: 05/12/2025] [Indexed: 05/29/2025] Open
Abstract
Bilirubin, albumin, and uric acid are established endogenous antioxidant biomarkers, whereas the antioxidant role of creatinine has not yet been fully clarified. As a byproduct of creatine metabolism, creatinine may reflect underlying metabolic activity and redox balance, particularly under conditions of oxidative stress such as cigarette smoking. This study aimed to evaluate the associations between serum creatinine and other antioxidant biomarkers and lung cancer risk, stratified by smoking status. We analyzed 83,371 cancer-free men from the Korean Cancer Prevention Study II (KCPS II) cohort. During a mean follow-up of 13.5 years, 533 incident lung cancer cases were identified. Serum creatinine, total bilirubin, albumin, and uric acid were measured. Smoking status classified participants as never-, former, and ever-smokers, with ever-smokers including both current and former smokers. Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), stratified by smoking status. Biomarkers were also analyzed by quartiles and linear trends. A single standard deviation increase in serum creatinine was significantly and inversely associated with lung cancer risk among former smokers (HR: 0.774, 95% CI: 0.620 to 0.967) and ever-smokers (HR: 0.823, 95% CI: 0.716 to 0.945). Total bilirubin also showed significant inverse associations in former smokers (HR: 0.826, 95% CI: 0.705 to 0.967) and ever-smokers (HR: 0.785, 95% CI: 0.708 to 0.870). Albumin was inversely associated only with ever-smokers (HR: 0.878, 95% CI: 0.807 to 0.955), while uric acid showed inverse associations with both former smokers (HR: 0.832, 95% CI: 0.699 to 0.989) and ever-smokers (HR: 0.847, 95% CI: 0.760 to 0.944). None of the biomarkers showed significant associations among never-smokers. Serum creatinine and other endogenous antioxidant biomarkers were inversely associated with lung cancer risk, particularly in individuals with a history of smoking exposure.
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Affiliation(s)
- Jong-Won Shin
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea;
- Department of Epidemiology and Health Promotion, Institute for Health Promotion, School of Public Health, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03772, Republic of Korea;
| | - Thien-Minh Nguyen
- Department of Epidemiology and Health Promotion, Institute for Health Promotion, School of Public Health, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03772, Republic of Korea;
- Department of Epidemiology, Faculty of Public Health, University of Medicine and Pharmacy, Ho Chi Minh City 17000, Vietnam
| | - Sun-Ha Jee
- Department of Epidemiology and Health Promotion, Institute for Health Promotion, School of Public Health, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03772, Republic of Korea;
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6
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Nalkiran I, Sevim Nalkiran H, Ozcelik N, Kivrak M. In Silico Identification of LSD1 Inhibition-Responsive Targets in Small Cell Lung Cancer. Bioengineering (Basel) 2025; 12:504. [PMID: 40428124 PMCID: PMC12108737 DOI: 10.3390/bioengineering12050504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2025] [Revised: 04/28/2025] [Accepted: 05/08/2025] [Indexed: 05/29/2025] Open
Abstract
Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy characterized by rapid progression, high metastatic potential, and limited therapeutic options. Lysine-specific demethylase 1 (LSD1) has been identified as a promising epigenetic target in SCLC. RG6016 (ORY-1001) is a selective LSD1 inhibitor currently under clinical investigation for its antitumor activity. In this study, publicly available RNA-Seq datasets from SCLC patient-derived xenograft (PDX) models treated with RG6016 were reanalyzed using bioinformatic approaches. Differential gene expression analysis was conducted to identify genes responsive to LSD1 inhibition. Candidate genes showing significant downregulation were further evaluated by molecular docking to assess their potential interaction with RG6016. The analysis identified a set of differentially expressed genes following RG6016 treatment, including notable downregulation of MYC, UCHL1, and TSPAN8. In silico molecular docking revealed favorable docking poses between RG6016 and the proteins encoded by these genes, suggesting potential direct or indirect targeting. These findings support a broader mechanism of action for RG6016 beyond its known interaction with LSD1. This study demonstrates that RG6016 may exert its antitumor effects through the modulation of additional molecular targets such as MYC, UCHL1, and TSPAN8 in SCLC. The combined bioinformatic and molecular docking analyses provide new insights into the potential multi-target profile of RG6016 and indicate the need for further experimental validation.
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Affiliation(s)
- Ihsan Nalkiran
- Department of Medical Biology, Faculty of Medicine, Recep Tayyip Erdogan University, 53020 Rize, Türkiye; (I.N.); (H.S.N.)
| | - Hatice Sevim Nalkiran
- Department of Medical Biology, Faculty of Medicine, Recep Tayyip Erdogan University, 53020 Rize, Türkiye; (I.N.); (H.S.N.)
| | - Neslihan Ozcelik
- Department of Chest Diseases, Faculty of Medicine, Recep Tayyip Erdogan University, 53020 Rize, Türkiye;
| | - Mehmet Kivrak
- Department of Biostatistics and Medical Informatics, Faculty of Medicine, Recep Tayyip Erdogan University, 53020 Rize, Türkiye
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Zhou J, Wang L, Bian C, Miao J, Han L, Qi C. Kartagener syndrome combined with small cell lung cancer: A case report and literature review. Exp Ther Med 2025; 29:98. [PMID: 40165801 PMCID: PMC11955821 DOI: 10.3892/etm.2025.12848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 01/22/2025] [Indexed: 04/02/2025] Open
Abstract
Kartagener syndrome (KS) is a rare autosomal recessive genetic disease characterized by visceral inversion, sinusitis and bronchiectasis. Small-cell lung cancer, a common tumor with poor prognosis, rarely coexists with KS. The lack of typical clinical symptoms can lead to missed or incorrect diagnoses, and to date, only few cases of this combination have been reported. The current study presents a case of KS with small cell lung cancer that was promptly diagnosed and treated at Jining No. 1 People's Hospital (Jining, China). Sharing this case may contribute to the advancement of respiratory medicine and aid doctors in the diagnosis and management of similar conditions.
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Affiliation(s)
- Jinhua Zhou
- Department of Pulmonary and Critical Care Medicine, Jining No. 1 People's Hospital, Jining, Shandong 272000, P.R. China
| | - Lei Wang
- Department of Pulmonary and Critical Care Medicine, Jining No. 1 People's Hospital, Jining, Shandong 272000, P.R. China
| | - Cuixia Bian
- Department of Pulmonary and Critical Care Medicine, Jining No. 1 People's Hospital, Jining, Shandong 272000, P.R. China
| | - Jianlong Miao
- Department of Pulmonary and Critical Care Medicine, Jining No. 1 People's Hospital, Jining, Shandong 272000, P.R. China
| | - Liping Han
- Department of Pulmonary and Critical Care Medicine, Jining No. 1 People's Hospital, Jining, Shandong 272000, P.R. China
| | - Congcong Qi
- Department of Pulmonary and Critical Care Medicine, Jining No. 1 People's Hospital, Jining, Shandong 272000, P.R. China
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8
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Nishioka R, Kawahara D, Imano N, Murakami Y. A nomogram-based survival prediction model for non-small cell lung cancer patients based on clinical risk factors and multiregion radiomics features. Clin Radiol 2025; 84:106826. [PMID: 40088854 DOI: 10.1016/j.crad.2025.106826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 12/06/2024] [Accepted: 01/02/2025] [Indexed: 03/17/2025]
Abstract
AIM This study focuses on developing a nomogram-based overall survival (OS) prediction model for non-small cell lung cancer (NSCLC) patients by integrating clinical factors with multiregion radiomics features extracted from pretreatment CT images. The proposed nomogram aims to assist clinicians in stratifying patients into high- and low-risk groups for personalised treatment strategies. MATERIALS AND METHODS From 2008 to 2018, 77 NSCLC patients were included. The radiomics feature was extracted from the internal and peripheral tumour region of pretreatment computed tomography (CT) images. The least absolute shrinkage and selection operator (LASSO) and the univariable Cox regression model were used to select the radiomics features. The Rad-score was defined as a linear combination of the selected radiomics features and the Cox proportional hazards regression coefficients. The combined model was constructed based on the clinicopathological factors and the Rad-score. The discrimination capacity of the prediction model was evaluated by Harrell's concordance index (C-index), the calibration curve, and the Kaplan-Meier survival curve. RESULTS We found that nine radiomics features and histology were independent predictors. The combined model showed the best performance (C-index: 0.799 [95% CI: 0.726-0.872]) compared with the clinical model (C-index: 0.692 [95% CI: 0.625-0.759]) and Rad-score (C-index: 0.663 [95% CI: 0.580-0.746]), and could significantly stratify into high-risk and low-risk NSCLC patients. The calibration curve also showed good consistency between the observation and the prediction. CONCLUSIONS The multregion radiomics features have the potential for predicting OS in NSCLC patients. The nomogram-based survival prediction model demonstrates significant potential in guiding clinical decision-making, allowing for precise and personalised treatment for NSCLC patients.
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Affiliation(s)
- R Nishioka
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - D Kawahara
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
| | - N Imano
- Department of Radiation Oncology, Hiroshima University Hospital, Hiroshima 734-8551, Japan
| | - Y Murakami
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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Lei X, Zheng Y, Su W. RNA-binding proteins and autophagy in lung cancer: mechanistic insights and therapeutic perspectives. Discov Oncol 2025; 16:599. [PMID: 40272614 PMCID: PMC12022210 DOI: 10.1007/s12672-025-02413-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 04/16/2025] [Indexed: 04/27/2025] Open
Abstract
BACKGROUND Lung cancer remains a leading cause of cancer-related mortality worldwide. Its progression is intricately associated with the dynamic regulation of autophagy and RNA-binding proteins (RBPs), which play crucial roles in mRNA stability, alternative splicing, and cellular stress responses. OBJECTIVES This review aims to systematically analyze the mechanisms through which RBPs and autophagy contribute to lung cancer progression and explore potential therapeutic strategies targeting these pathways. METHODS We reviewed recent studies on the molecular mechanisms by which RBPs regulate tumor proliferation, metabolic adaptation, and their interaction with autophagy. The review also examines the dual roles of autophagy in lung cancer, highlighting its context-dependent effects on cell survival and death. RESULTS The interactions and regulatory networks between RBPs and autophagy involve multiple levels of regulation. RBPs can directly influence autophagy processes and act as microRNA (miRNA) sponges to regulate mRNA stability. The modulation of RBPs affects the expression of autophagy-related genes (ATGs) and autophagosome formation. Additionally, RBPs participate in complex regulatory interactions with non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other proteins. CONCLUSIONS This review proposes innovative therapeutic strategies that combine RBP-targeting approaches (e.g., small molecule inhibitors, CRISPR gene editing) with autophagy modulators (e.g., mTOR inhibitors, chloroquine) to enhance treatment efficacy. Nanoparticle drug delivery systems and epigenetic regulation offer further opportunities for targeted interventions. This review lays a theoretical foundation for advancing lung cancer research and provides novel insights into synergistic therapies that target both RBPs and autophagy to improve treatment outcomes for lung cancer.
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Affiliation(s)
- Xiao Lei
- Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong, China
- Zhanjiang Key Laboratory of Tumor Microenvironment and Organoid Research, Zhanjiang, 524001, China
- Department of Guangdong Medical University, Zhanjiang, 524023, China
| | - Yuexin Zheng
- Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong, China
- Zhanjiang Key Laboratory of Tumor Microenvironment and Organoid Research, Zhanjiang, 524001, China
- Department of Guangdong Medical University, Zhanjiang, 524023, China
| | - Wenmei Su
- Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong, China.
- Zhanjiang Key Laboratory of Tumor Microenvironment and Organoid Research, Zhanjiang, 524001, China.
- Department of Guangdong Medical University, Zhanjiang, 524023, China.
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10
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Zhang J, Ma X, Liu Z, Wang H, Lu B, Wang Z. Exploring the Impact of Neuroticism on Lung Cancer Risk: Insights From Mediated Mendelian Randomization. Brain Behav 2025; 15:e70482. [PMID: 40259690 PMCID: PMC12012258 DOI: 10.1002/brb3.70482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 03/18/2025] [Accepted: 03/25/2025] [Indexed: 04/23/2025] Open
Abstract
OBJECTIVE This study aimed to explore the potential association between neuroticism and lung cancer. METHODS We conducted analyses on publicly accessible aggregated data from genome-wide association studies (GWAS) that included individuals of European descent. The objective was to identify single nucleotide polymorphisms (SNPs) significantly associated with neuroticism and utilize them as instrumental variables in a two-sample Mendelian randomization framework to evaluate the gender-specific causal link between neuroticism and lung cancer risk. We applied four statistical methods: Inverse variance weighting (IVW), weighted median, MR-Egger regression, and weighted mode. Our analysis also considered the mediating effect of educational attainment on this relationship. RESULTS We selected 67 SNPs associated with neuroticism at genome-wide significance levels from GWAS datasets. Our primary findings using IVW suggest a notable increase in lung cancer risk associated with neuroticism across the general population (odds ratio [OR] = 1.175; 95% confidence interval [CI] 1.020-1.354, p = 0.026). Gender-specific analysis revealed that neuroticism posed a slight but significant risk increase in men (OR = 1.006; 95% CI 1.000-1.012, p = 0.045) and women (OR = 1.005; 95% CI 1.002-1.009, p = 0.002), with findings corroborated by the additional statistical methods. Further, evidence from both observational and Mendelian randomization analyses suggests that genetically predicted neuroticism is causally associated with a modestly increased risk of incident lung cancer, with ∼17% of this effect mediated by educational attainment. CONCLUSIONS The results from this Mendelian randomization study provide robust evidence supporting a potential association between neuroticism and an increased risk of lung cancer. This association appears more pronounced in men than women. Additionally, educational level serves as a mediator in the nexus between these conditions, suggesting that interventions aimed at increasing educational attainment might mitigate some of the risk neuroticism poses for developing lung cancer.
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Affiliation(s)
- Jie Zhang
- Department of OncologyThe Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Xiao Ma
- Department of OncologyThe Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Zhiyu Liu
- Department of OncologyThe Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - He Wang
- Department of OncologySir Run Run HospitalNanjing Medical UniversityNanjingChina
| | - Binbin Lu
- Department of OncologyThe Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Zhaoxia Wang
- Department of OncologyThe Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
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Flash M, Lynch EA, Lacson R, Guenette JP, Desai S, Kapoor N. Predictors of Physician Agreement With Radiologist-Recommended Follow-up Imaging. J Am Coll Radiol 2025; 22:407-416. [PMID: 39551329 DOI: 10.1016/j.jacr.2024.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 11/01/2024] [Accepted: 11/12/2024] [Indexed: 11/19/2024]
Abstract
OBJECTIVE Although recommendations for additional imaging are common in radiology reports, completion of follow-up imaging does not always occur, which could reflect disagreement between radiologist and referring provider. We assessed how frequently referring providers agree with radiologists' follow-up recommendations, reasons for disagreement, and factors associated with radiologist-referring provider agreement. METHODS This institutional review board-exempt, retrospective study was performed at a large academic center. A PACS-integrated tool allowed radiologists to send follow-up imaging recommendations to referring providers, who used the tool to document agreement or disagreement with recommendations. The study included recommendations sent for outpatients between October 21, 2019, and October 31, 2022. Multivariable logistic regression analysis was performed to identify patient, radiologist, and imaging examination factors associated with radiologist-referring provider agreement. RESULTS Of the 9,406 recommendations meeting inclusion criteria, 8,331 (88.6%) resulted in agreement. The most common reason for disagreement was that the recommendation was considered not clinically relevant (44.5%, 478 of 1,075). The following factors were associated with low rates of agreement: referring provider being a surgeon (odds ratio [OR] 0.73, P < .001) or recommendation for follow-up nuclear imaging (OR 0.64, P = .012). The odds of agreement were higher for recommendations made by thoracic radiologists (OR 1.41, P = .002) and for recommendations with longer follow-up time frames (weeks) (OR 1.03, P < .001). Patient race, ethnicity, insurance type, and living in a socio-economically disadvantaged neighborhood were not significantly associated with radiologist-referring provider agreement. DISCUSSION Referring providers frequently agree with follow-up imaging recommendations made by radiologists for outpatients, and patient demographics and socio-economic factors do not seem to significantly impact radiologist-referring provider agreement.
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Affiliation(s)
- Moses Flash
- Department of Radiology, Hospital of the University of Pennsylvania, University of Pennsylvania Health System, Philadelphia, Pennsylvania
| | - Elyse A Lynch
- Center for Evidence-Based Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Ronilda Lacson
- Center for Evidence-Based Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Jeffrey P Guenette
- Center for Evidence-Based Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Sonali Desai
- Vice President, Quality, and Associate Chief Medical Officer, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Neena Kapoor
- Associate Chair of Quality and Safety, Center for Evidence-Based Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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12
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Panpan SI, Wei GE, Kaiming WU, Zhang R. O-GlcNAcylation of hexokinase 2 modulates mitochondrial dynamics and enhances the progression of lung cancer. Mol Cell Biochem 2025; 480:2633-2643. [PMID: 39496915 PMCID: PMC11961486 DOI: 10.1007/s11010-024-05146-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 10/21/2024] [Indexed: 11/06/2024]
Abstract
Non-small cell lung cancer (NSCLC) stands as the prevailing manifestation of lung cancer, with current therapeutic modalities linked to a dismal prognosis, necessitating further advancements. Hexokinase 2 (HK2), a critical enzyme positioned on the mitochondrial membrane, exerts control over diverse biological pathways, thereby regulating cancer. Nevertheless, the precise role and mechanism of HK2 in NSCLC remain inadequately elucidated, warranting comprehensive investigation. HK2 expression in NSCLC tissues and cell lines was detected through immunohistochemistry and western blot analysis. Concurrently, shRNA assays were applied to scrutinize the impact of HK2 on cell proliferation, apoptosis, migration, and invasion processes in NSCLC cell lines, utilizing CCK8, flow cytometry, wound-healing assay, and transwell techniques. The involvement of HK2 in mitochondrial dynamics was probed through western blot analysis, mitochondrial membrane potential assay, and assessment of ROS generation. Next, the functional role of HK2 was assessed by examining its influence on xenograft tumor growth in nude mice in vivo. Further research has demonstrated that HK2 played a role in NSCLC through its O-GlcNAcylation process. The results of the study revealed that HK2 O-GlcNAcylation promoted the proliferation, migration, and invasive characteristics of NSCLC cells, while alleviating mitochondrial damage, whereas O-GlcNAcylation inactivation yielded the opposite effect. Furthermore, in vivo experiments in nude mice illustrated that HK2 O-GlcNAcylation could stimulate tumor growth in NSCLC. These results suggested that HK2 may impact mitochondrial dynamics in NSCLC through its O-GlcNAcylation, thereby contributing to the progression of NSCLC.
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Affiliation(s)
- S I Panpan
- Department of Chest Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230031, Anhui, China
| | - G E Wei
- Department of Chest Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230031, Anhui, China
| | - W U Kaiming
- Department of Chest Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230031, Anhui, China
| | - Renquan Zhang
- Department of Chest Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230031, Anhui, China.
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13
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Hao L, Zhang J, Di Y, Qi Z, Zhang P. Predicting a failure of postoperative thromboprophylaxis in non-small cell lung cancer: A stacking machine learning approach. PLoS One 2025; 20:e0320674. [PMID: 40168285 PMCID: PMC11960935 DOI: 10.1371/journal.pone.0320674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Accepted: 02/21/2025] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND Non-small-cell lung cancer (NSCLC) and its surgery significantly increase the venous thromboembolism (VTE) risk. This study explored the VTE risk factors and established a machine-learning model to predict a failure of postoperative thromboprophylaxis. METHODS This retrospective study included patients with NSCLC who underwent surgery between January 2018 and November 2022. The patients were randomized 7:3 to the training and test sets. Nine machine learning models were constructed. The three most predictive machine-learning classifiers were chosen as the first layer of the stacking machine-learning model, and logistic regression was the second layer of the meta-learning model. RESULTS This study included 362 patients, including 58 (16.0%) with VTE. Based on the multivariable logistic regression analysis, age, platelets, D-dimers, albumin, smoking history, and epidermal growth factor receptor (EGFR) exon 21 mutation were used to develop the nine machine-learning models. LGBM Classifier, RandomForest Classifier, and GNB were chosen for the first layer of the stacking machine learning model. The area under the received operating characteristics curve (ROC-AUC), accuracy, sensitivity, and specificity of the stacking machine learning model in the training/test set were 0.984/0.979, 0.949/0.954, 0.935/1.000, and 0.958/0.887, respectively. In the validation set, the final stacking machine learning model demonstrated an ROC AUC of 0.983, accuracy of 0.937, sensitivity of 0.978, and specificity of 0.947. The decision curve analyses revealed high benefits. CONCLUSION The stacking machine learning model based on EGFR mutation and clinical characteristics had a predictive value for postoperative VTE in patients with NSCLC.
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Affiliation(s)
- Ligang Hao
- Department of Thoracic Surgery, Xingtai People’s Hospital, Xingtai, Hebei, China
| | - Junjie Zhang
- Department of Computed Tomography and Magnetic Resonance, Xingtai People’s Hospital, Xingtai, Hebei, China
| | - Yonghui Di
- Department of Thoracic Surgery, Xingtai People’s Hospital, Xingtai, Hebei, China
| | - Zheng Qi
- Department of Clinical Lab, Xingtai People’s Hospital, Xingtai, Hebei, China
| | - Peng Zhang
- Department of Thoracic Surgery, Xingtai People’s Hospital, Xingtai, Hebei, China
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14
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Chen J, Li C, Yu Y, Liu S, Hu Q, Cai C, Luo J, Wu Y, Tu Z. Global epidemiological trends of trachea, bronchus, and lung cancer in the elderly. Cancer Epidemiol 2025; 95:102760. [PMID: 39904714 DOI: 10.1016/j.canep.2025.102760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/28/2024] [Accepted: 01/28/2025] [Indexed: 02/06/2025]
Abstract
BACKGROUND Despite most patients with trachea, bronchus, and lung (TBL) cancer being elderly, epidemiological data specific to this population remain scarce. This study aims to update and delineate the global epidemiological profile of TBL in older adults. METHODS An analysis was conducted on data from the Global Burden of Diseases (GBD) 2021 for individuals aged 60 and older. We evaluated the worldwide impact of TBL cancer by socio-demographic index (SDI), gender, and age across 204 countries and territories, including their spatial and temporal trends. The main outcomes comprised age-standardized incidence rates (ASIR), mortality rates (ASMR), disability-adjusted life years (DALY) rates (ASDR), and average annual percent change (AAPC). RESULTS From 1992 to 2021, the estimated cases of TBL cancer, along with associated deaths and DALYs, increased among the elderly. The ASIR, ASMR, and ASDR all exhibited a declining trend. In 2021, East Asia faced a substantial TBL cancer burden, whereas Western Sub-Saharan Africa exhibited a notable increase over the last thirty years. In 2021, Monaco and Greenland recorded the highest ASIR, ASMR, and ASDR, while Egypt experienced the most significant rise in these rates from 1992 to 2021. The greatest affected age group was those aged 85-89. The TBL cancer burden followed distinct patterns by SDI and sex, with higher SDI regions and females facing a particularly notable increase in burden. From 1992 to 2021, smoking was the leading risk factor for TBL cancer-related deaths and DALYs in older adults, with particulate matter air pollution as a close second. CONCLUSIONS The burden of TBL cancer varies widely across different regions and demographics. More attention should be paid to the elderly in higher SDI regions and females. Recognizing these trends is crucial for enhancing tertiary prevention strategies for TBL cancer and exploring innovative approaches to diagnosis and treatment.
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Affiliation(s)
- Jintu Chen
- Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, No. 248 East Street, Quanzhou City, Fujian 362000, PR China
| | - Caili Li
- Day Surgery Center, General Practice Medical Center, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Yang Yu
- Division of Thoracic Tumor Multimodality Treatment and Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Shanghai Liu
- Division of Thoracic Tumor Multimodality Treatment and Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China; West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Qipeng Hu
- German Cancer Research Center (DKFZ), Heidelberg University, Heidelberg, Germany
| | - Chengzhi Cai
- Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, Zhejiang 310003, PR China
| | - Jieyan Luo
- Cancer Center, Ziyang Central Hospital, No. 66, Rende West Road, Yanjiang District, Ziyang City, Sichuan Province, PR China
| | - Yijun Wu
- Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
| | - Zegui Tu
- Division of Thoracic Tumor Multimodality Treatment and Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China; West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
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15
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Lee WR, Ha KS. Mitochondrial Ribosomal Protein S17 Silencing Inhibits Proliferation and Invasiveness of Lung Cancer Cells. J Cancer Prev 2025; 30:47-55. [PMID: 40201023 PMCID: PMC11973458 DOI: 10.15430/jcp.24.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 01/10/2025] [Accepted: 01/15/2025] [Indexed: 04/10/2025] Open
Abstract
Chromosomal alterations are frequent events in lung cancer progression. Although gains and losses of chromosomal position have been reported, the association between copy number alteration and lung cancer patient survival has not been extensively investigated. In this study, we performed a meta-analysis of public cBioPortal datasets spanning 25 lung cancer studies to identify putative cancer driver genes with copy number alterations associated with overall patient survival. Ten copy-number altered genes enriched in deceased lung cancer patients were identified. Seven of these putative driver genes were located in the 7p11.2 chromosomal location, and two were in the 9p21.3 cytoband. Among these genes, the mitochondrial ribosomal protein S17 (MRPS17) amplification was significantly associated with a lower patient survival rate (P = 1.47e-7). To investigate the functional role of MRPS17, small interfering RNA-mediated knockdown was performed in two non-small cell lung cancer cell lines, A549 and NCI-H460. MRPS17 knockdown significantly reduced cell proliferation, migration, invasion, and anchorage-independent growth in both cell lines. Furthermore, knockdown of MRPS17 decreased the activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, suggesting its role in driving lung cancer progression through this critical oncogenic pathway. Our findings highlight MRPS17 as a potential cancer therapy target and a prognostic biomarker that may improve the survival rates of lung cancer patients. Future studies should explore its inhibition as a therapeutic strategy as well as elucidate its molecular mechanisms in cancer progression.
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Affiliation(s)
- Woo Rin Lee
- Department of Chemistry, The University of Suwon, Hwaseong, Korea
| | - Kook Sun Ha
- Department of Chemistry, The University of Suwon, Hwaseong, Korea
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16
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Wang B, Zhou X, Wu D, Gao L, Wan Z, Wu R. Development and validation of M2 macrophage-related genes in a prognostic model of lung adenocarcinoma based on bulk RNA and ScRNA datasets. Discov Oncol 2025; 16:352. [PMID: 40100580 PMCID: PMC11920479 DOI: 10.1007/s12672-025-02123-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 03/11/2025] [Indexed: 03/20/2025] Open
Abstract
OBJECTIVE This study aimed to investigate the correlation between M2 macrophages activity with the prognosis of lung adenocarcinoma (LUAD). We sought to identify key genes associated with M2 macrophage activity and examine their relationship with clinicopathological features to elucidate the underlying mechanism. METHODS Published datases were analyzed for differentially expressed genes. After quality control, batch effect removal, and annotation, the scRNA dataset identified M2 macrophage-associated differentially expressed genes in the LUAD group, which were cross-analyzed and referred to as M2 macrophage-linked genes. A risk model was generated using machine learing for these genes. Thereafter, two bulk RNA-seq datasets were used to evaluate the model. We computed risk scores for all samples and grouped them into low and high risk, aiding in the comparison of clinical characteristics, immune and stromal infiltration, and drug sensitivity. Finally, key genes were validated through immunohistochemistry in IPA samples. RESULTS We identified four key M2 macrophage-linked genes: TIMP1, CAV2, MIF, and SELENBP1. Survival durations in the high-riskscore cluster were lower across the TCGA-LUAD (P = 1.2 × 10-4), GSE14814 (P = 0.02), and GSE37745 (P = 0.01) data sets. The stromal score, fibroblast infiltration, and cytokinesis activation were increased in the high-risk subgroup. Neutrophil and endothelial cell infiltration and activation of the linolenic acid pathway occurred in the low-risk group. IHC confirmed that CAV2 and SELENBP1 expression was significantly reduced, while TIMP1 and MIF were significantly increased in LUAD, which was consistent with the bioinformatics findings. CONCLUSION The role of M2 macrophages in tumor progression could anticipate the prognosis of LUAD and develop novel immunotherapy strategies.
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Affiliation(s)
- Bolin Wang
- Graduate School of Chengde Medical College, Chengde, Hebei, China
- Department of Chest Surgery, Baoding First Central Hospital, Baoding, Hebei, China
| | - Xiaofeng Zhou
- Department of Chest Surgery, Baoding First Central Hospital, Baoding, Hebei, China
| | - Di Wu
- Department of Chest Surgery, Baoding First Central Hospital, Baoding, Hebei, China
| | - Lu Gao
- Department of Chest Surgery, Baoding First Central Hospital, Baoding, Hebei, China
| | - Zhihua Wan
- Department of Chest Surgery, Baoding First Central Hospital, Baoding, Hebei, China
| | - Ruifeng Wu
- Department of Chest Surgery, Baoding First Central Hospital, Baoding, Hebei, China.
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17
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Yue C, San C, Deng S, Wang J, Shen X, Wang H, Huang L, Bu R, Wang D. Jidangga-7 ameliorates non-small cell lung cancer by regulating gut microbiota function. Front Microbiol 2025; 16:1516685. [PMID: 40109975 PMCID: PMC11919877 DOI: 10.3389/fmicb.2025.1516685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 02/10/2025] [Indexed: 03/22/2025] Open
Abstract
Objective This study aims to assess the effects of Jidangga-7 on enhancing gut microbiota function in non-small cell lung cancer. Materials and methods Eighteen mice were screened and randomly divided into three groups: a control group, a model group with induced non-small cell lung cancer, and a treatment group receiving Jidangga-7. A549 tumor cells were implanted in the mice, and tumor formation was monitored. Upon successful tumor induction, the treatment group received Jidangga-7 via oral gavage, while the other groups received an equivalent volume of saline. After the final dose, intestinal tissues were collected from each group, and microbial amplicon 16S analysis and non-extensive targeted metabolomics were employed to characterize intestinal fiber and associated metabolites. Results By quantifying the contribution of individual species to the variations between the groups, the Sipmer results highlighted the top 10 species and their abundance that contribute to the differences between the two groups. Specifically, Jidangga-7 demonstrated a regulatory effect on various taxa such as Gammaproteobacteria, Bacilli, and Desulfovovoviridae. At the family level, administration of Jidangga-7 exhibited a regulatory effect on families including Desulfovibrionaceae, Lachnospiraceae, and Eggerthellaceae, compared to the model group. In untargeted metabolomics analyses, principal component analysis effectively differentiated the groups from one another. Subsequently, metabolites with a variable importance in projection score > 1 were screened. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed 20 metabolite pathways, encompassing metabolism of cofactors and vitamins, bacterial metabolism, antimicrobial pathways, and xenobiotics biodegradation and metabolism. Conclusion Jidangga-7 exerted a positive influence on the intestinal microbial environment in mice with non-small cell carcinoma, ameliorating the dysbiosis induced by non- small cell lung cancer. This intervention inhibited the growth of pathogenic bacteria while fostering the growth of beneficial strains.
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Affiliation(s)
- Changcheng Yue
- Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China
| | - Chula San
- Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China
| | - Shichao Deng
- Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China
| | - Jingjing Wang
- Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China
| | - Xueying Shen
- Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China
| | - Hongqing Wang
- Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China
| | - Liyan Huang
- Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China
| | - Renbatu Bu
- Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China
| | - Dong Wang
- Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China
- Clinical Research Centre for Malignant Tumours of Mongolian Medicine in Inner Mongolia Autonomous Region, Tongliao, China
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18
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Juang YR, Ang L, Seow WJ. Predictive performance of risk prediction models for lung cancer incidence in Western and Asian countries: a systematic review and meta-analysis. Sci Rep 2025; 15:4259. [PMID: 40038330 PMCID: PMC11880538 DOI: 10.1038/s41598-024-83875-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 12/18/2024] [Indexed: 03/06/2025] Open
Abstract
Numerous prediction models have been developed to identify high-risk individuals for lung cancer screening, with the aim of improving early detection and survival rates. However, no comprehensive review or meta-analysis has assessed the performance of these models across different sociocultural contexts. Therefore, this review systematically examines the performance of lung cancer risk prediction models in Western and Asian populations. PubMed and EMBASE were searched from inception through January 2023. Studies published in English that proposed a validated model on human populations with well-defined predictive performances were included. Two reviewers independently screened the titles and abstracts, and the Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess study quality. A random-effects meta-analysis was performed, and a 95% confidence interval (CI) for model performance was reported. Between-study heterogeneity was adjusted for using the Hartung-Knapp-Sidik-Honkman test. A total of 54 studies were included, with 42 from Western countries and 12 from Asian countries. Most Western studies focused on ever-smokers (19/42; 45.2%) and the general population (17/42; 40.5%), and only two Asian studies developed models exclusively for never-smokers. Across both Western and Asian prediction models, the three most consistently included risk factors were age, sex, and family cancer history. In 45.2% (19/42) of Western and 50.0% (6/12) of Asian studies, models incorporated both traditional risk factors and biomarkers. In addition, 14.8% (8/54) of the studies directly compared biomarker-based models with those incorporating only traditional risk factors, demonstrating improved discrimination. Machine-learning algorithms were applied in eight Western models and two Asian models. External validation of PLCOM2012 (AUC = 0.748; 95% CI: 0.719-0.777) outperformed other prediction models, such as Bach (AUC = 0.710; 95% CI: 0.674-0.745) and Spitz models (AUC = 0.698; 95% CI: 0.640-0.755). Despite showing promising results, the majority of Asian risk models in our study lack external validation. Our review also highlights a significant gap in prediction models for never-smokers. Future research should focus on externally validating existing Asian models or incorporating relevant Asian risk factors into widely used Western models (PLCOM2012) to better account for unique risk profiles and lung cancer progression patterns in Asian populations.
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Affiliation(s)
- Yah Ru Juang
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 117549, Singapore
| | - Lina Ang
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 117549, Singapore
| | - Wei Jie Seow
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 117549, Singapore.
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, 119228, Singapore.
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Alaoui Abdalaoui Slimani F, Bentourkia M. Improving deep learning U-Net++ by discrete wavelet and attention gate mechanisms for effective pathological lung segmentation in chest X-ray imaging. Phys Eng Sci Med 2025; 48:59-73. [PMID: 39495449 DOI: 10.1007/s13246-024-01489-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 10/09/2024] [Indexed: 11/05/2024]
Abstract
Since its introduction in 2015, the U-Net architecture used in Deep Learning has played a crucial role in medical imaging. Recognized for its ability to accurately discriminate small structures, the U-Net has received more than 2600 citations in academic literature, which motivated continuous enhancements to its architecture. In hospitals, chest radiography is the primary diagnostic method for pulmonary disorders, however, accurate lung segmentation in chest X-ray images remains a challenging task, primarily due to the significant variations in lung shapes and the presence of intense opacities caused by various diseases. This article introduces a new approach for the segmentation of lung X-ray images. Traditional max-pooling operations, commonly employed in conventional U-Net++ models, were replaced with the discrete wavelet transform (DWT), offering a more accurate down-sampling technique that potentially captures detailed features of lung structures. Additionally, we used attention gate (AG) mechanisms that enable the model to focus on specific regions in the input image, which improves the accuracy of the segmentation process. When compared with current techniques like Atrous Convolutions, Improved FCN, Improved SegNet, U-Net, and U-Net++, our method (U-Net++-DWT) showed remarkable efficacy, particularly on the Japanese Society of Radiological Technology dataset, achieving an accuracy of 99.1%, specificity of 98.9%, sensitivity of 97.8%, Dice Coefficient of 97.2%, and Jaccard Index of 96.3%. Its performance on the Montgomery County dataset further demonstrated its consistent effectiveness. Moreover, when applied to additional datasets of Chest X-ray Masks and Labels and COVID-19, our method maintained high performance levels, achieving up to 99.3% accuracy, thereby underscoring its adaptability and potential for broad applications in medical imaging diagnostics.
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Affiliation(s)
| | - M'hamed Bentourkia
- Department of Nuclear Medicine and Radiobiology, 12th Avenue North, 3001, Sherbrooke, QC, J1H5N4, Canada.
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20
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Lone AH, Salunkhe R, Sugumar V, Zhan LJ, Ye XY, Bezjak A, Cho J, Giuliani ME, Hope AJ, Sun A, Raman S, Bradbury PA, Eng L, Leighl NB, Shepherd FA, Sacher A, Liu G, Lok BH. Real-world outcomes of prophylactic cranial irradiation utilization and efficacy for patients with extensive-stage small cell lung cancer treated with consolidative thoracic radiotherapy. Clin Transl Radiat Oncol 2025; 51:100917. [PMID: 39898331 PMCID: PMC11787411 DOI: 10.1016/j.ctro.2025.100917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 09/11/2024] [Accepted: 01/06/2025] [Indexed: 02/04/2025] Open
Abstract
Background The role of prophylactic cranial irradiation (PCI) is not well-defined in extensive-stage SCLC (ES-SCLC), with conflicting results from randomized trials and a lack of relevant data for patients who received consolidative thoracic radiotherapy (CTRT). We sought to evaluate the impact of PCI on the outcomes of ES-SCLC patients who were all treated with CTRT. Methods A retrospective analysis of ES-SCLC patients without brain metastases who were all treated with CTRT between 2013-2021 at our institution was conducted. Overall survival (OS) and incidence of brain failure (BFR) were estimated using Kaplan-Meier estimation and cumulative incidence function. Multivariable Cox or Fine-Gray's proportional hazard regression analysis (MVA) were performed to determine association between PCI and OS. Results 47 patients met inclusion criteria and were theoretically eligible for PCI, 27 (57.4 %) received PCI and CTRT while 20 (42.6 %) received CTRT alone. Baseline characteristics were similar except for age, where patients receiving PCI were younger (median age 62) compared to patients who did not receive PCI (median age 72). Median OS with PCI was 19.2 months, compared to 10.8 months without PCI (P = 0.0334). This improved OS remained apparent in patients who received post-chemotherapy MRI restaging (P = 0.0245). BFR was reduced with PCI (HR = 0.22 [0.09-0.52], P = 0.0004). On MVA, PCI was significantly and independently associated with improved OS (HR = 0.39 [0.19-0.80], P = 0.01) and reduced BFR (HR = 0.20 [0.09-0.44], P = < 0.001). Conclusion This real-world study found PCI was independently associated with improved OS and reduced BFR in ES-SCLC patients treated with CTRT compared to patients treated with CTRT not receiving PCI, including after post-chemotherapy brain MRI. The role of PCI with CTRT should be evaluated in prospective studies.
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Affiliation(s)
- Abdul H. Lone
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada
- William Carey University College of Osteopathic Medicine, Hattiesburg, MS, USA
| | - Rohan Salunkhe
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Vijithan Sugumar
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Luna J. Zhan
- Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Xiang Y. Ye
- Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Andrea Bezjak
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - John Cho
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Meredith E. Giuliani
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Andrew J. Hope
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Alexander Sun
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Srinivas Raman
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Penelope A. Bradbury
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Lawson Eng
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Natasha B. Leighl
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Frances A. Shepherd
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Adrian Sacher
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Geoffrey Liu
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Benjamin H. Lok
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada
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21
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Tian Q, Tian C, Lu Y, Yan B, Zhang K, Wu C. RETRACTED: Poly (lactic-co-glycolic acid)-encapsulated Endostar-loaded calcium phosphate cement as anti-tumor bone cement for the treatment of bone metastasis in lung cancer. ENVIRONMENTAL TOXICOLOGY 2025; 40:E17-E30. [PMID: 38400521 DOI: 10.1002/tox.24166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 01/14/2024] [Accepted: 01/20/2024] [Indexed: 02/25/2024]
Abstract
Lung cancer is one of the most common malignant tumors in the world. In approximately 30%-40% of lung cancer patients, bone metastases ensues with osteolytic destruction. Worse still, intractable pain, pathological fracture, and nerve compression caused by bone metastases are currently the bottleneck of research, diagnosis, and treatment of lung cancer. Therefore, the present study aims at investigating the effectiveness of a new composite material made of calcium phosphate cement (CPC) and Endostar on repairing bone defects in vitro and in vivo. As indicated in results, the mechanical properties of CPC+Endostar and CPC+PLGA+Endostar do not differ from those of pure CPC. The PLGA-embedded Endostar slow-release microspheres were designed and prepared, and were combined with CPC. Poly (lactic-co-glycolic acid (PLGA) is a biodegradable polymer material in vivo, so the effect on its mechanical properties is negligible. CPC+Endostar and CPC+PLGA+Endostar have been proved to inhibit cell proliferation, promote apoptosis and block cell cycle in G2 phase; the expression levels of osteoclast-related genes CXCL2, TGF-β1, IGF-1, IL-6, and RANKL were significantly decreased while osteogenic ability and alkaline phosphatase activity observably enhanced. In vivo studies have revealed that the expression levels of TRAP, RANKL, and Caspase3 in CPC+PLGA+ENDO-treated tumor tissues after 3 weeks were higher than those in other groups with the prolongation of animal treatment time, while the expression levels of OPN and BCL2 were lower than those in other groups. In hematoxylin and eosin and TUNEL staining, 3 weeks of CPC+PLGA+ENDO-treatment yielded higher tissue necrosis and apoptosis than other groups; computed tomography and magnetic resonance imaging results showed the posterior edge bone damage reduced as a result of the CPC+PLGA+ENDO grafting in vertebral pedicle. Overall, the feasibility and reliability of CPC-loaded Endostar in the treatment of bone metastasis in lung cancer were investigated in this study, so as to promote the basic research and treatment of bone metastasis in lung cancer and other malignant tumors.
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Affiliation(s)
- QingHua Tian
- Department of Diagnostic and Interventional Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Cong Tian
- Department of Oncology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - YingYing Lu
- Department of Diagnostic and Interventional Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - BiCong Yan
- Department of Diagnostic and Interventional Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kaixian Zhang
- Department of Oncology, Tengzhou Central People's Hospital Affiliated to Jining Medical College, Tengzhou, China
| | - ChunGen Wu
- Department of Diagnostic and Interventional Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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22
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Zhang X, Zou J, Ning J, Qu R, Zhao Y, Lv C, Liang Y, Zhang Y. Disease burden of trachea, bronchus and lung cancer 1990-2021 and global trends projected to 2035. Sci Rep 2025; 15:6264. [PMID: 39979494 PMCID: PMC11842633 DOI: 10.1038/s41598-025-90537-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 02/13/2025] [Indexed: 02/22/2025] Open
Abstract
Tracheal, bronchial, and lung cancer (TBL) is among the most common malignancies worldwide, with persistently high incidence and mortality rates, posing a significant threat to public health. However, existing studies on TBL disease burden are often limited to specific regions or short-term trends, lacking systematic and predictive analyses. This study comprehensively evaluated the global, regional, and national burden of TBL across 204 countries and territories from 1990 to 2021, utilizing predictive models to estimate trends from 2022 to 2035. This study used data from the Global Burden of Disease (GBD) 2021 database to systematically analyze the prevalence (ASPR), incidence (ASIR), mortality (ASMR), and disability-adjusted life years (DALYs) associated with TBL. Age-standardized rates (ASR) were used to quantify disease burden. Historical trends were assessed using Joinpoint regression analysis, while ARIMA and Bayesian age-period-cohort (BAPC) models were employed to predict future trends. The study also incorporated the Sociodemographic Index (SDI) to investigate the impact of socioeconomic development on TBL burden. In 2021, the global ASPR, ASIR, ASMR, and DALYs for TBL were 37.28, 26.43, 23.50, and 638.60 per 100,000 population, respectively. From 1990 to 2021, ASPR increased slightly (0.09 per 100,000), while ASIR, ASMR, and DALYs declined by 0.07, 0.15, and 0.23 per 100,000, respectively. Regionally, the highest ASPR was observed in the high-income Asia-Pacific region (69.79 per 100,000), while East Asia recorded the highest ASIR (43.41 per 100,000) and ASMR (38.53 per 100,000). Sub-Saharan Africa had the lowest burden. Gender analysis showed that males had a significantly higher TBL burden than females, but their burden declined over the study period. In contrast, females, particularly in older age groups, experienced an increase in burden. Future predictions indicate that the overall TBL burden will decline between 2022 and 2035; however, the burden among females and older adults is projected to rise, with a marked increase in female ASPR. This study highlights the global and regional trends in TBL burden from 1990 to 2021 and provides predictions for future burden. Although the overall burden is declining, significant disparities exist across genders and regions, with East Asia and high-income North America warranting particular attention. Females and older adults are priority groups for future interventions. The findings underscore the importance of early screening, targeted interventions, and region-specific strategies to optimize public health policies, resource allocation, and tailored prevention efforts.
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Affiliation(s)
- Xin Zhang
- College of Basic Medical sciences, Dali University, Dali, 671000, China
| | - Jing Zou
- Department of Respiratory Medicine, The First Affiliated Hospital of Dali University, Dali, 671000, China
| | - Jinghua Ning
- College of Basic Medical sciences, Dali University, Dali, 671000, China
| | - Run Qu
- College of Basic Medical sciences, Dali University, Dali, 671000, China
| | - Yanhong Zhao
- College of Basic Medical sciences, Dali University, Dali, 671000, China
| | - Congcong Lv
- College of Basic Medical sciences, Dali University, Dali, 671000, China
| | - Yi Liang
- Princess Margaret Cancer Centre, TMDT-MaRS Centre, University Health Network, Toronto, ON, Canada
| | - Yuzhe Zhang
- College of Basic Medical sciences, Dali University, Dali, 671000, China.
- Key Laboratory of Anti-Pathogen Medicinal Plants Screening, Dali, 671000, Yunnan Province, China.
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23
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Shen Y, Dong X, Li X, Shi Z, Shao T, Jiang J, Song J. WNT inhibitor SP5-mediated SERPING1 suppresses lung adenocarcinoma progression via TSC2/mTOR pathway. Cell Death Dis 2025; 16:103. [PMID: 39962118 PMCID: PMC11832940 DOI: 10.1038/s41419-025-07440-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 01/25/2025] [Accepted: 02/11/2025] [Indexed: 02/20/2025]
Abstract
The long-term outlook for patients grappling with lung cancer (LC) remains bleak, with lung adenocarcinoma (LUAD) emerging as the most predominant histological subtype. Our Mendelian randomization (MR) investigation spotlighted that heightened levels of the circulating protein serpin peptidase inhibitor family G1 (SERPING1) substantially mitigated LC risk. The fusion of multi-omics strategies unveiled that SERPING1 exhibited diminished expression in LUAD patients compared to healthy individuals both in tissues and serum, with LUAD individuals showcasing elevated SERPING1 expression demonstrating improved prognoses. Furthermore, SERPING1 expression exhibited a robust correlation with the efficacy of immunotherapy. Through meticulous in vivo and in vitro analyses, we unraveled that SERPING1 impeded the proliferation, migration, invasion and wound healing of LUAD cells via the tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR) pathway. Mechanistically, WNT inhibitor- Specificity Protein (SP5) was delineated as facilitator of SERPING1 transcription by binding to the SERPING1 gene promoter. Intriguingly, aside from the association between SERPING1 and systolic blood pressure, glycosylated hemoglobin (HbA1c), type I diabetes, no discernible link between SERPING1 overexpression and heightened risks of other cardiometabolic conditions and diseases was evident. In summary, SERPING1 emerges as a novel tumor suppressor gene and SP5/SERPING1/TSC2 is a promising therapeutic target in the context of LUAD.
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Affiliation(s)
- Yefeng Shen
- Institute of Cardiovascular Sciences, Guangxi Academy of Medical Sciences, Nanning, China
- Department of Thoracic Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiaofeng Dong
- Department of Hepatobiliary, Pancreas and Spleen Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region (Guangxi Academy of Medical Sciences), Nanning, China
| | - Xujia Li
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zhiyuan Shi
- School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, China
| | - Tingting Shao
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Junlan Jiang
- Department of Pathology, the First Affiliated Hospital, Anhui Medical University, Hefei, China
- Pathology Center, Anhui Medical University, Hefei, China
| | - Jian Song
- Institute of Cardiovascular Sciences, Guangxi Academy of Medical Sciences, Nanning, China.
- Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
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24
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Tesema GA, Tessema ZT, Heritier S, Stirling RG, Earnest A. Timeliness of Lung Cancer Care and Area-Level Determinants in Victoria: A Bayesian Spatiotemporal Analysis. Cancer Epidemiol Biomarkers Prev 2025; 34:308-316. [PMID: 39540823 DOI: 10.1158/1055-9965.epi-24-0205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 05/23/2024] [Accepted: 11/11/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND The reports have stated that the timeliness of lung cancer care varies significantly across different regions. According to the Victorian Lung Cancer Registry report, the timeliness of lung cancer care in Victoria has changed over time. Therefore, we aimed to quantify the extent of these spatial inequalities over time and to identify area-level determinants contributing to these changes. METHODS The study analyzed lung cancer cases reported to the Victorian Lung Cancer Registry between 2011 and 2022. Bayesian spatiotemporal conditional autoregressive models were fitted, incorporating spatial random effects, temporal random effects, and spatiotemporal interactions. The best performing model was selected using the deviance information criterion. For the final best fit model, the adjusted RRs and their 95% credible intervals were reported. RESULTS More than half (51.24%) of patients with lung cancer experienced treatment delays, whereas approximately one third (30.98%) encountered diagnostic delays. Moderate spatiotemporal variations were observed in both delayed diagnosis and treatment. In the final best fit model for treatment delay, an increase in the percentage of smokers was significantly associated with a higher risk of treatment delay (RR = 2.13; 95% credible interval, 1.13-4.20). CONCLUSIONS Identifying high-risk areas provides useful information for policymakers, helping in the reduction of delays in lung cancer diagnosis and treatment. IMPACT This study has revealed spatiotemporal inequalities in diagnostic and treatment delays, providing valuable insights for identifying areas that should be prioritized to ensure timely care for lung cancer.
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Affiliation(s)
- Getayeneh Antehunegn Tesema
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Zemenu Tadesse Tessema
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Stephane Heritier
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Rob G Stirling
- Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
- Department of Respiratory Medicine, Alfred Health, Melbourne, Australia
| | - Arul Earnest
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
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25
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Léna H, Greillier L, Cropet C, Bylicki O, Monnet I, Audigier-Valette C, Falchero L, Vergnenègre A, Demontrond P, Geier M, Guisier F, Hominal S, Locher C, Corre R, Chouaid C, Ricordel C. Nivolumab plus ipilimumab versus carboplatin-based doublet as first-line treatment for patients with advanced non-small-cell lung cancer aged ≥70 years or with an ECOG performance status of 2 (GFPC 08-2015 ENERGY): a randomised, open-label, phase 3 study. THE LANCET. RESPIRATORY MEDICINE 2025; 13:141-152. [PMID: 39486424 DOI: 10.1016/s2213-2600(24)00264-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 08/08/2024] [Accepted: 08/08/2024] [Indexed: 11/04/2024]
Abstract
BACKGROUND Combined treatment with anti-PD-1 and anti-CTLA-4 antibodies has shown superiority over chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC), but data for older patients (aged ≥70 years) with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or those with an ECOG performance status of 2 are scarce. We aimed to test the superiority of the PD-1 antibody nivolumab and the CTLA-4 antibody ipilimumab over platinum-based doublet chemotherapy as first-line treatment in patients with NSCLC aged 70 years or older or with an ECOG performance status of 2. METHODS This open-label, multicentre, randomised, controlled, phase 3 trial was done at 30 hospitals and cancer centres in France. Eligible patients had stage IV histologically proven NSCLC, with no known oncogenic alterations, and were either aged 70 years or older with ECOG performance status of 0-2 or younger than 70 years with an ECOG performance status of 2. Patients were randomly assigned (1:1) centrally, using a computer-generated algorithm stratified by age (<70 vs ≥70 years), ECOG performance status (0-1 vs 2), and histology (squamous vs non-squamous) to receive nivolumab plus ipilimumab or platinum-based doublet chemotherapy (carboplatin [area under the curve ≤700 mg] plus pemetrexed [500 mg/m2 intravenous infusion every 3 weeks] or carboplatin [on day 1; area under the curve ≤700 mg] plus paclitaxel [90 mg/m2 as intravenous infusion on days 1, 5, and 15, every 4 weeks]). The primary endpoint was overall survival; secondary endpoints included progression-free survival and safety. All efficacy analyses were performed in the intention-to-treat population, which included all randomly assigned patients. Safety was analysed in the safety analysis set, which included all randomly assigned patients who received at least one dose of study treatment and who had at least one safety follow-up. The trial is registered with ClinicalTrials.gov, NCT03351361. FINDINGS The trial was stopped early for futility on the basis of a pre-planned interim analysis after 33% of the expected events had occurred. Between Feb 12, 2018, and Dec 15, 2020, 217 patients were randomly assigned, of whom 216 patients were included in the final analysis, with 109 patients in the nivolumab plus ipilimumab group and 107 in the chemotherapy group; median age was 74 years (IQR 70-78). Median overall survival was 14·7 months (95% CI 8·0-19·7) in the nivolumab plus ipilimumab group and 9·9 months (7·7-12·3) in chemotherapy group (hazard ratio [HR] 0·85 [95% CI 0·62-1·16]). Among patients aged 70 years or older with an ECOG performance status of 0-1 (median age 76 years [IQR 73-79]), median overall survival was longer in the nivolumab plus ipilimumab group than the chemotherapy group: 22·6 months (95% CI 18·1-36·0) versus 11·8 months (8·9-20·5; HR 0·64 [95% CI 0·46-0·96]). Among patients with an ECOG performance status of 2 (median age 69 years [IQR 63-75]), median overall survival was 2·9 months (95% CI 1·4-4·8) in the nivolumab plus ipilimumab group versus 6·1 months (3·5-10·4) in the chemotherapy group (HR 1·32 [95% CI 0·82-2·11]). No new safety signals were reported. The most frequent grade 3 or worse adverse events were neutropenia (28 [27%] of 103 patients) in the chemotherapy group and endocrine disorders (five [5%] of 105 patients), cardiac disorders (ten [10%] patients), and gastrointestinal disorders (11 [11%] patients) in the nivolumab plus ipilimumab group. INTERPRETATION The study showed no benefit of nivolumab plus ipilimumab combination in the overall study population. As a result of early stopping, the trial was underpowered for primary and secondary endpoints; however, the finding of better survival with nivolumab plus ipilimumab compared with platinum doublet in the subgroup of older patients with NSCLC with an ECOG performance status of 0-1 warrants further study. FUNDING Bristol-Myers Squibb.
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Affiliation(s)
- Hervé Léna
- Service de Pneumologie, Centre Hospitalier Universitaire de Rennes, Université Rennes 1, INSERM, UMR_S 1242, Centre Eugène Marquis, Rennes, France.
| | - Laurent Greillier
- Multidisciplinary Oncology and Therapeutic Innovations, Aix-Marseille University, APHM, INSERM, CNRS, CRCM, Hôpital Nord, Marseille, France
| | - Claire Cropet
- Unité de Biostatistique-Direction de la Recherche et de l'Innovation, Centre Léon Bérard, Lyon, France
| | | | - Isabelle Monnet
- Service de Pneumologie, Centre Hospitalier Intercommunal Créteil, Créteil, France
| | | | - Lionel Falchero
- Service de Pneumologie et Cancérologie Thoracique, Hôpitaux Nord-Ouest, Villefranche sur Saône, France
| | - Alain Vergnenègre
- Unité d'Oncologie Thoracique, Centre Hospitalier Universitaire Dupuytren, Limoges, France
| | | | - Margaux Geier
- Institut de Cancérologie et Imagerie, Hopital Cavale Blanche Centre Hospitalier Universitaire Brest, Brest, France
| | - Florian Guisier
- Service de Pneumologie, Centre Hospitalier Universitaire Rouen, Rouen, France
| | - Stéphane Hominal
- Service de Pneumologie, Centre Hospitalier Annecy Genevois, Epagny Metz-Tessy, France
| | - Chrystèle Locher
- Service de Pneumologie, Grand Hôpital de l'Est Francilien (Meaux), Meaux, France
| | - Romain Corre
- Centre Hospitalier de Cornouaille, Service de Pneumologie, Quimper, France
| | - Christos Chouaid
- Service de Pneumologie, Centre Hospitalier Intercommunal Créteil, Créteil, France
| | - Charles Ricordel
- Service de Pneumologie, Centre Hospitalier Universitaire de Rennes, Université Rennes 1, INSERM, UMR_S 1242, Centre Eugène Marquis, Rennes, France
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26
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Buğday İ, İnanç M, Özkan M, Bozkurt O, Coşar R, Firat ST, Mutlu E, Eser M, Dişli AK, Cengiz M. Prognostic impact of elevated C-reactive protein and procalcitonin in patients with extensive-stage small cell lung cancer. Anticancer Drugs 2025; 36:135-139. [PMID: 39601772 DOI: 10.1097/cad.0000000000001670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
Small cell lung cancer (SCLC) constitutes around 15% of lung cancer cases and stands as the primary cause of cancer-related fatalities in men and the second leading cause in women globally. In this study, our objective was to evaluate the levels of C-reactive protein (CRP) and procalcitonin (PCT) in newly diagnosed extensive-stage SCLC patients without evidence of infection. We aimed to demonstrate that elevated CRP and PCT levels may not solely indicate infection but could also be elevated in malignancies. Furthermore, we sought to correlate these marker levels with patient and disease characteristics to elucidate the relationship between these inflammation markers and disease progression. A total of 115 patients who were pathologically and radiologically diagnosed with extensive-stage SCLC between January 2020 and December 2022 and who had received no prior treatment were included in the study. The Kaplan-Meier analysis revealed a median progression-free survival (PFS) of 7.46 months [95% confidence interval (CI), 6.85-8.07] and a median overall survival (OS) of 10.50 months (95% CI, 8.69-12.30) for all patients. In the group with elevated PCT, the median PFS was 6.73 months (95% CI, 3.92-9.54), whereas it was 7.86 months (95% CI, 7.13-8.59) in the group with normal PCT ( P = 0.002). Similarly, the median OS was 9.10 months (95% CI, 5.61-12.58) in the elevated PCT group and 11.66 months (95% CI, 9.59-13.74) in the normal PCT group ( P = 0.006). Patients with elevated procalcitonin (PRC) levels at the time of diagnosis exhibited shorter PFS and OS durations compared to patients with normal PRC levels. Furthermore, elevated CRP has also been demonstrated to correlate with poorer prognosis in extensive-stage SCLC.
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Affiliation(s)
- İrfan Buğday
- Medical Oncology Department, Erciyes University Medical School, Kayseri, Türkiye
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Li Z, Fan M, Zhou Z, Sang X. Circ_0082374 Promotes the Tumorigenesis and Suppresses Ferroptosis in Non-small Cell Lung Cancer by Up-Regulating GPX4 Through Sequestering miR-491-5p. Mol Biotechnol 2025; 67:484-495. [PMID: 38438754 DOI: 10.1007/s12033-024-01059-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 01/02/2024] [Indexed: 03/06/2024]
Abstract
Circular RNAs (circRNAs) have been identified to be dysregulated in non-small cell lung cancer (NSCLC) and implicated in the progression of this cancer. Here, this work aimed to investigate the role and mechanism of circ_0082374 on NSCLC progression. Levels of circ_0082374, miR-491-5p, GPX4 (glutathione peroxidase 4) and epithelial-mesenchymal transition (EMT)-related proteins were examined by quantitative real-time PCR or western blotting, respectively. Cell proliferation and metastasis were detected using cell counting kit-8, colony formation, EdU, transwell, and Scratch assays. Cell ferroptosis was evaluated by measuring cell survival after the treatment of different ferroptosis inducers or inhibitors, as well as the accumulation of intracellular reactive oxygen species (ROS), ferrous iron (Fe2+) and malondialdehyde (MDA). The binding between miR-491-5p and circ_0082374 or GPX4 was confirmed using dual-luciferase reporter and RNA pull-down assays. In vivo experiments were conducted using murine xenograft assay and immunohistochemistry. Circ_0082374 was a stable circRNA with high expression in NSCLC tissues and cells. Functionally, circ_0082374 silencing suppressed NSCLC cell proliferation and metastasis. Moreover, its down-regulation enhanced ferroptosis by decreasing iron and lipid peroxidation accumulation. Mechanistically, circ_0082374 could indirectly up-regulate GPX4 expression via miR-491-5p, indicating the circ_0082374/miR-491-5p/GPX4 competitive endogenous RNAs (ceRNA) network. Rescue experiments demonstrated that the miR-491-5p/GPX4 axis mediated the regulatory effects of circ_0082374 exerted on NSCLC cells. Moreover, knockdown of circ_0082374 impeded NSCLC growth and EMT via regulating miR-491-5p and GPX4. Circ_0082374 silencing could suppress NSCLC cell proliferation, metastasis and induce ferroptosis through miR-491-5p/GPX4 axis, suggesting a novel therapeutic approach for NSCLC patients.
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Affiliation(s)
- Zongyu Li
- Department of Pulmonary and Critical Care Medicine, Shulan(Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, 310022, Zhejiang, China
| | - Mengdi Fan
- Department of General Practice, Shulan(Hangzhou) Hospital Affiliated to Zhejiang, Shuren University Shulan International Medical College, Hangzhou, 310022, Zhejiang, China
| | - Zhibo Zhou
- Department of Infectious, Shulan(Hangzhou) Hospital Affiliated to Zhejiang, Shuren University Shulan International Medical College, Hangzhou, 310022, Zhejiang, China
| | - Xianyin Sang
- Department of Respiratory Therapy, Shulan(Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, 848 Dongxin Rd., Hangzhou, 310022, Zhejiang, People's Republic of China.
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28
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Toma C, Popa R, Ciobanu L, Baldea I, Amorim I, Bochynska D, Wolfe A, Negoescu A, Gal C, Taulescu M. Overexpression of IL-6 and STAT3 may provide new insights into ovine pulmonary adenocarcinoma development. BMC Vet Res 2025; 21:29. [PMID: 39833798 PMCID: PMC11744984 DOI: 10.1186/s12917-024-04429-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 12/04/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Ovine pulmonary adenocarcinoma (OPA) is caused by Jaagsiekte sheep retrovirus (JSRV) and is considered an important potential animal model for human lung cancer. The precise mechanisms of OPA oncogenesis are still uncertain. The transcription factor signal transducer and activator of transcription 3 (STAT3) is activated by interleukin-6 (IL-6) in many cancers, but this aspect is unknown in OPA. We therefore aimed to evaluate the expression of IL-6 and STAT3 in OPA for its potential role in pulmonary carcinogenesis. RESULTS Lung tissues from 9 grossly normal and JRSV-negative sheep and 20 cases of JSRV-positive OPA sheep were included in the study. Tissue samples were stained with antibodies against IL-6, STAT3, and JSRV-MA. IL-6 and STAT3 were further quantified in both groups using Western Blot (WB). Immunohistochemically, IL‑6 was expressed in stromal, inflammatory, and epithelial cells in all cases of OPA, while STAT3 immunoexpression was restricted to epithelial cells. In the OPA group, the percentage of immunolabelled cells for STAT3 accounted for a mean value of 96%. Using the H-SCORE method, 95% of cases were considered positive for STAT3 expression. Control tissues showed multifocal and weak immunoexpression for both markers. Using WB analyses, a highly significant amount of both IL-6 (p = 0.0078) and STAT3 (p < 0.0001) proteins were present in lung neoplasms, by comparison to the control lungs. CONCLUSIONS Our data showed overexpression of IL-6 and STAT3 in lung tissues from OPA compared to lungs from JSRV-negative sheep. These results suggest a potential role of IL6-STAT3 in OPA carcinogenesis.
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Affiliation(s)
- Corina Toma
- Department of Veterinary Pathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania.
| | - Roxana Popa
- Department of Veterinary Pathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania
| | - Lidia Ciobanu
- Regional Institute of Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj-Napoca, Romania
| | - Ioana Baldea
- Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj- Napoca, Romania
| | - Irina Amorim
- Department of Pathology and Molecular Immunology of the Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
- Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal
| | - Diana Bochynska
- Ross University School of Veterinary Medicine, Basseterre, St. Kitts and Nevis
| | - Alan Wolfe
- Pathobiology Section, School of Veterinary Medicine, University College Dublin, Dublin, Ireland
| | - Andrada Negoescu
- Department of Veterinary Pathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania
| | - Claudiu Gal
- Department of Veterinary Pathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania
- Synevovet laboratory, Bucharest, Romania
| | - Marian Taulescu
- Department of Veterinary Pathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania
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Farrag MS, Abdelwahab HW, Abdellateef A, Anber N, Ellayeh MA, Hussein DT, Eldesoky AR, Sheta H. DNA mismatch repair (MMR) genes expression in lung cancer and its correlation with different clinicopathologic parameters. Sci Rep 2025; 15:885. [PMID: 39762286 PMCID: PMC11704133 DOI: 10.1038/s41598-024-83067-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 12/11/2024] [Indexed: 01/11/2025] Open
Abstract
Lung cancer (LC) is a crucial rapidly developing disease. In Egypt, it is one of the five most frequent cancers. Little is known about the impact of deleted mismatch repair genes and its correlation to clinicopathological characteristics. This study evaluates immunohistochemical expression of the mismatch repair genes (PMS2), (MSH2), (MLH1) & (MSH6) & its correlation with clinicopathologic parameters & prognosis of LC. Age was higher with lost MLH1 & PMS2 but HTN was higher with lost four markers. Smoking was associated with expression of MLH1 & PMS2. A progressive course was associated with lost MSH2 & MSH6. Suprarenal metastasis was associated with lost all markers but bone metastasis was associated with lost MSH2 & MSH6. All the markers were significantly correlated with each other, with perfect correlations between MSH6 & MSH2 and between MLH & PMS2. Median overall survival among cases with lost markers was significantly lower than patients with preserved markers. We recommend evaluation of the four proteins as a biomarker that could guide LC therapy. In-depth biological research is imperative to elucidate the precise roles and mechanisms of these markers. This will advance management strategies and even guide immune checkpoint inhibitor therapy for LC.
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Affiliation(s)
- Mayada Saad Farrag
- Pathology Department, Port Said Faculty of Medicine, Port Said University, Port Said, Egypt.
| | | | - Amr Abdellateef
- Cardiothoracic Surgery Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Nahla Anber
- Emergency Hospital, Mansour University, Mansoura, Egypt
| | | | - Dalia Tawfeek Hussein
- Children's Hospital, Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Faculty of Medicine, Tobruk University, Tobruk, Libya
| | - Ahmed Ramadan Eldesoky
- Clinical Oncology and Nuclear Medicine Department, Mansoura Faculty of Medicine, Mansoura, Egypt
| | - Heba Sheta
- Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Yang H, Hua J, Han Y, Chang D, Zheng W. Development and preliminary validation of five miRNAs for lung adenocarcinoma prognostic model associated with immune infiltration. Sci Rep 2025; 15:528. [PMID: 39747924 PMCID: PMC11695782 DOI: 10.1038/s41598-024-84128-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 12/20/2024] [Indexed: 01/04/2025] Open
Abstract
Our aim was to investigate the potential value of immune-related miRNA signaling in predicting clinical prognosis and immunotherapy. We first identified immune-related miRNAs in lung adenocarcinoma (LUAD), and then constructed a miRNA-based risk model by lasso regression modeling. Finally, we validated our findings using RT-qPCR in serum from LUAD patients and normal patients. Weighted gene co-expression network analysis (WGCNA) was used to screen the aberrantly expressed genes associated with immune scores, and then correlation analysis and prognostic analysis were used to identify and immune-associated miRNAs, and lasso-cox regression was used to construct an immune-associated 5-miRNA model. Risk score as an independent prognostic factor could accurately predict the prognosis of LUAD patients. Immunotherapy analysis revealed that patients with low-risk scores benefited more from anti-PD-1 and CTLA-4 therapy. Experimental validation showed that only miRNA-200b-3p was significantly differentially expressed in 91 cases of clinically collected cancer tissues and normal tissue serum. We constructed a 5-miRNA model that can be used for risk stratification of LUAD patients. Targeted therapy against miRNA-200b-3p is expected to be a prospective new strategy for the clinical treatment of LUAD.
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Affiliation(s)
- Huanzhang Yang
- Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
| | - Jingli Hua
- Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
| | - Yanxia Han
- Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
| | - Dong Chang
- Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
| | - Wenlong Zheng
- Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
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Feng J, Shao X, Gao J, Ge X, Sun Y, Shi Y, Wang Y, Niu R. Application and progress of non-invasive imaging in predicting lung invasive non-mucinous adenocarcinoma under the new IASLC grading guidelines. Insights Imaging 2025; 16:4. [PMID: 39747759 PMCID: PMC11695567 DOI: 10.1186/s13244-024-01877-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 11/30/2024] [Indexed: 01/04/2025] Open
Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide, with invasive non-mucinous adenocarcinoma (INMA) being the most common type and carrying a poor prognosis. In 2020, the International Association for the Study of Lung Cancer (IASLC) pathology committee proposed a new histological grading system, which offers more precise prognostic assessments by combining the proportions of major and high-grade histological patterns. Accurate identification of lung INMA grading is crucial for clinical diagnosis, treatment planning, and prognosis evaluation. Currently, non-invasive imaging methods (such as CT, PET/CT, and MRI) are increasingly being studied to predict the new grading of lung INMA, showing promising application prospects. This review outlines the establishment and prognostic efficiency of the new IASLC grading system, highlights the application and latest progress of non-invasive imaging techniques in predicting lung INMA grading, and discusses their role in personalized treatment of lung INMA and future research directions. CRITICAL RELEVANCE STATEMENT: The new IASLC grading system has important prognostic implications for patients with lung invasive non-mucinous adenocarcinoma (INMA), and non-invasive imaging methods can be used to predict it, thereby improving patient prognoses. KEY POINTS: The new IASLC grading system more accurately prognosticates for patients with lung INMA. Preoperative prediction of the new grading is challenging because of the complexity of INMA subtypes. It is feasible to apply non-invasive imaging methods to predict the new IASLC grading system.
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Affiliation(s)
- Jinbao Feng
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Institute of Clinical Translation of Nuclear Medicine and Molecular Imaging, Soochow University, Changzhou Key Laboratory of Molecular Imaging, Changzhou, China
| | - Xiaonan Shao
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Institute of Clinical Translation of Nuclear Medicine and Molecular Imaging, Soochow University, Changzhou Key Laboratory of Molecular Imaging, Changzhou, China
| | - Jianxiong Gao
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Institute of Clinical Translation of Nuclear Medicine and Molecular Imaging, Soochow University, Changzhou Key Laboratory of Molecular Imaging, Changzhou, China
| | - Xinyu Ge
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Institute of Clinical Translation of Nuclear Medicine and Molecular Imaging, Soochow University, Changzhou Key Laboratory of Molecular Imaging, Changzhou, China
| | - Yan Sun
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Institute of Clinical Translation of Nuclear Medicine and Molecular Imaging, Soochow University, Changzhou Key Laboratory of Molecular Imaging, Changzhou, China
| | - Yunmei Shi
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Institute of Clinical Translation of Nuclear Medicine and Molecular Imaging, Soochow University, Changzhou Key Laboratory of Molecular Imaging, Changzhou, China
| | - Yuetao Wang
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Institute of Clinical Translation of Nuclear Medicine and Molecular Imaging, Soochow University, Changzhou Key Laboratory of Molecular Imaging, Changzhou, China
| | - Rong Niu
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Institute of Clinical Translation of Nuclear Medicine and Molecular Imaging, Soochow University, Changzhou Key Laboratory of Molecular Imaging, Changzhou, China.
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Guo Q, He Y, Chen S, Hu S, Wang S, Su L, Zhang W, Xu J, Wei Y, Luo G. Development and validation of nomogram for predicting the cancer-specific survival among patients aged 80 and above with early-stage non-small cell lung cancer. ANZ J Surg 2025; 95:106-116. [PMID: 39392183 DOI: 10.1111/ans.19266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 08/08/2024] [Accepted: 09/29/2024] [Indexed: 10/12/2024]
Abstract
BACKGROUND The use of nomograms in predicting the prognosis of early-stage non-small cell lung cancer (NSCLC), particularly in elderly patients, is not widespread. A validated prognostic model specifically for NSCLC patients over 80 years old holds promising potential for clinical application in forecasting patient outcomes. METHODS The prognostic value of various factors for NSCLC patients aged 80 and above was evaluated using data from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2017). Kaplan-Meier (KM) curves, Cox proportional hazards regression models, and nomogram were utilized to evaluate the impact of each factor on cancer-specific survival (CSS). RESULTS A cohort comprising 7045 individuals was selected for inclusion in the analysis. Through rigorous statistical analysis, 10 independent prognostic factors were identified and incorporated into the nomogram. The nomogram's receiver operating characteristic (ROC) curve area under the curve (AUC) was higher than that of the AJCC 7th edition TNM staging system's predicted CSS (0.744 versus 0.602), establishing the superior prognostic value of the nomogram. CONCLUSIONS We have successfully created a highly accurate and discriminative nomogram that enables oncologists to predict the survival outcome of each individual patient with I/II NSCLC who is 80 years or older.
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Affiliation(s)
- Qiang Guo
- Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, China
| | - Yuan He
- Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, China
| | - Shai Chen
- Department of Vascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, China
| | - Sheng Hu
- Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, China
| | - Silin Wang
- Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, China
| | - Lang Su
- Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, China
| | - Wenxiong Zhang
- Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, China
| | - Jianjun Xu
- Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, China
| | - Yiping Wei
- Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, China
| | - Guiping Luo
- Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, China
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Yang L, Li A, Yu W, Wang H, Zhang L, Wang D, Wang Y, Zhang R, Lei Q, Liu Z, Zhen S, Qin H, Liu Y, Yang Y, Song XL, Zhang Y. Blockade of purine metabolism reverses macrophage immunosuppression and enhances anti-tumor immunity in non-small cell lung cancer. Drug Resist Updat 2025; 78:101175. [PMID: 39608215 DOI: 10.1016/j.drup.2024.101175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 11/17/2024] [Accepted: 11/21/2024] [Indexed: 11/30/2024]
Abstract
AIMS Immune checkpoint blockade therapy is not effective in most patients with non-small cell lung cancer (NSCLC) due to the immunosuppressive tumor microenvironment. Macrophages are key components of tumor-infiltrating immune cells and play a critical role in immunosuppression, which can be mediated by cell-intrinsic metabolism. This study aimed to evaluate whether macrophages regulate NSCLC progression through metabolic crosstalk with cancer cells and affect immunotherapy efficacy. METHODS The macrophage landscape of NSCLC tissues were analyzed by single-cell sequencing and verified through flow cytometry and immunofluorescence. Multiplex assay, single-cell sequencing data, ELISA, immunofluorescence, and RNA-seq et al. were used to investigate and verify the mechanism of macrophage-mediated metabolic regulation on immunosuppression. The tumor-bearing model was established in C57BL/6 J mice to explore in vivo efficacy. RESULTS We found that tumor tissue-derived macrophages exhibited an anti-inflammatory phenotype and had a prognostic value for NSCLC. NSCLC cell-secreted CXCL8 recruited macrophages from peritumor tissues to tumor sites and promoted programmed death-ligand 1 (PD-L1) expression by activating purine metabolism with increasing xanthine dehydrogenase and uric acid production. Moreover, purine metabolism-mediated macrophage immunosuppression was dependent on NLRP3/caspase-1/IL-1β signaling. Blockade of purine metabolism signaling enhanced anti-tumor immunity and the efficacy of anti-PD-L1 therapy. CONCLUSIONS Collectively, our findings reveal a key role of purine metabolism in macrophage immunosuppression and suggest that blockade of purine metabolism combined with immune checkpoint blockade could provide synergistic effects in NSCLC treatment.
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Affiliation(s)
- Li Yang
- Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou, Henan, China; School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.
| | - Aitian Li
- Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Weina Yu
- Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Huishang Wang
- Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Lei Zhang
- Thoracic Surgery Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Dan Wang
- Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Ying Wang
- Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Ru Zhang
- Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Qingyang Lei
- Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Zhangnan Liu
- Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Shanshan Zhen
- Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Haiming Qin
- Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yaqing Liu
- Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yang Yang
- Thoracic Surgery Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Xian-Lu Song
- Department of Radiotherapy, Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
| | - Yi Zhang
- Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou, Henan, China; School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China; Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China; School of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
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Shen K, Shan Z, Li Y, Ji Z, Zhou L, Lv Z. TFAP2A Activates ADAM8 to Promote Lung Adenocarcinoma Angiogenesis Through the JAK/STAT Signaling Pathway. J Biochem Mol Toxicol 2025; 39:e70097. [PMID: 39812116 DOI: 10.1002/jbt.70097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 09/10/2024] [Accepted: 12/08/2024] [Indexed: 01/16/2025]
Abstract
As the most prevalent subtype of lung cancer, lung adenocarcinoma (LUAD) is closely associated with angiogenesis, which is fundamental to its progression. ADAM8 (A disintegrin and metalloproteinase 8) is an enzyme associated with tumor invasion, while its implications in LUAD angiogenesis are a field that awaits exploration. A thorough investigation into the impacts of ADAM8 on LUAD angiogenesis could contribute to the development of therapeutic drugs for LUAD. Bioinformatics delineated the expression profiles of TFAP2A and ADAM8 in LUAD tissues, focusing on ADAM8-enriched pathways. qRT-PCR confirmed their expression in LUAD cells. The CCK-8 assay was applied to gauge cell viability, and Western blot detected the presence of JAK2/STAT3 pathway proteins and VEGFR-2 and VEGF. Angiogenesis assays quantified the length of angiogenesis, and dual-luciferase and Chromatin immunoprecipitation assays verified the TFAP2A-ADAM8 binding. ADAM8 exhibited high expression in LUAD tissues and cells, with notable enrichment in the VEGF and JAK/STAT pathways. Cellular assays revealed that elevated ADAM8 expression enhanced cell viability, promoted the phosphorylation of JAK2 and STAT3, and boosted angiogenic capacity. The JAK inhibitor Peficitinib reversed the proangiogenic effects induced by ADAM8 overexpression. We also discovered overexpression of TFAP2A, an upstream transcription factor of ADAM8, in LUAD. Rescue experiments indicated that ADAM8 overexpression could counteract the inhibitory effects of TFAP2A knockdown on LUAD angiogenesis. This study reveals for the first time the critical role of ADAM8 in LUAD angiogenesis, demonstrating that TFAP2A promotes JAK/STAT pathway conduction by activating ADAM8. This finding not only provides a new perspective for understanding the pathogenesis of LUAD but also lays the foundation for the development of new therapies targeting ADAM8.
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Affiliation(s)
- Kai Shen
- Department of Two Branches Outside, The First People's Hospital of Yongkang, Yongkang, China
| | - Zhidong Shan
- Department of Two Branches Outside, The First People's Hospital of Yongkang, Yongkang, China
| | - Yingjie Li
- Department of Two Branches Outside, The First People's Hospital of Yongkang, Yongkang, China
| | - Zeyi Ji
- Department of Two Branches Outside, The First People's Hospital of Yongkang, Yongkang, China
| | - Luyao Zhou
- Department of Two Branches Outside, The First People's Hospital of Yongkang, Yongkang, China
| | - Zhiliang Lv
- Department of Two Branches Outside, The First People's Hospital of Yongkang, Yongkang, China
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Anyimadu EA, Engelbart JM, Semprini J, Kahl A, Trentz C, Buatti JM, Casavant TL, Charlton ME, Canahuate G. Racial Disparities in Cancer Guideline-Concordant Treatment Using Surveillance, Epidemiology, and End Results Data for Patients With NSCLC. JTO Clin Res Rep 2025; 6:100747. [PMID: 39758596 PMCID: PMC11699381 DOI: 10.1016/j.jtocrr.2024.100747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/05/2024] [Accepted: 10/12/2024] [Indexed: 01/07/2025] Open
Abstract
Introduction Despite efforts to achieve health care equality, racial/ethnic disparities persist in lung cancer survival in the United States, with non-Hispanic Black patients experiencing higher mortality compared with non-Hispanic Whites. Previous research often focused on single treatments, overlooking the broad range of options available. We aimed to highlight disparities in survival and receipt of comprehensive lung cancer treatment by developing a guideline-concordant initial treatment (GCIT) indicator based on disease stage and recommended treatment. Methods Using data of the Surveillance, Epidemiology, and End Results on 377,370 patients with NSCLC, we derived a GCIT indicator based on National Comprehensive Cancer Network guidelines. Observed probabilities and logistic regression models adjusted for age, disease stage, and race were used to assess racial disparities in treatment and survival, with the Kaplan-Meier method evaluating survival rates. Racial/ethnic groups analyzed included non-Hispanic White, non-Hispanic Black, Asian/Pacific Islander, Hispanic, and American Indian/Alaska Native. Results Non-Hispanic Black patients had lower odds of receiving GCIT (OR = 0.80; 95% confidence interval [CI]: 0.78-0.82) and surviving 2 years after diagnosis (OR = 0.80; 95% CI: 0.78-0.82). Non-Hispanic Asians had the highest odds of receiving GCIT (OR = 1.02; 95% CI: 0.99-1.05). Patients receiving GCIT had improved survival, with early stage patients experiencing median survival of 67 to 102 months, compared with 11 to 17 months for those without GCIT. Conclusion Receiving GCIT considerably improves survival across all races, though disparities in receipt are observed. Interventions are needed to ensure equitable access to guideline-concordant care and reduce survival disparities for patients.
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Affiliation(s)
- Eric Ababio Anyimadu
- Department of Electrical and Computer Engineering, University of Iowa, Iowa City, Iowa
| | - Jacklyn M. Engelbart
- Department of Epidemiology, University of Iowa, Iowa City, Iowa
- Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa
| | - Jason Semprini
- Department of Public Health, Des Moines University, Des Moines, Iowa
| | - Amanda Kahl
- Department of Epidemiology, University of Iowa, Iowa City, Iowa
| | - Cameron Trentz
- Department of Electrical and Computer Engineering, University of Iowa, Iowa City, Iowa
| | - John M. Buatti
- Department of Radiation Oncology, University of Iowa, Iowa City, Iowa
| | - Thomas L. Casavant
- Department of Electrical and Computer Engineering, University of Iowa, Iowa City, Iowa
| | | | - Guadalupe Canahuate
- Department of Electrical and Computer Engineering, University of Iowa, Iowa City, Iowa
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Kim SS, Cooke DT, Kidane B, Tapias LF, Lazar JF, Awori Hayanga JW, Patel JD, Neal JW, Abazeed ME, Willers H, Shrager JB. The Society of Thoracic Surgeons Expert Consensus on the Multidisciplinary Management and Resectability of Locally Advanced Non-small Cell Lung Cancer. Ann Thorac Surg 2025; 119:16-33. [PMID: 39424119 DOI: 10.1016/j.athoracsur.2024.09.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 09/09/2024] [Accepted: 09/26/2024] [Indexed: 10/21/2024]
Abstract
BACKGROUND The contemporary management and resectability of locally advanced lung cancer are undergoing significant changes as new data emerge regarding immunotherapy and targeted treatments. The objective of this document is to review the literature and present consensus among a group of multidisciplinary experts to guide the determination of resectability and management of locally advanced non-small cell lung cancer (NSCLC) in the context of contemporary evidence. METHODS The Society of Thoracic Surgeon Workforce on Thoracic Surgery assembled a multidisciplinary expert panel composed of thoracic surgeons and medical and radiation oncologists with established expertise in the management of lung cancer. A focused literature review was performed, and expert consensus statements were developed using a modified Delphi process to address 3 major themes: (1) assessing resectability and multidisciplinary management of locally advanced lung cancer, (2) neoadjuvant (including perioperative) therapy, and (3) adjuvant therapy. RESULTS A consensus was reached on 19 recommendations. These consensus statements reflect updated insights on resectability and multidisciplinary management of locally advanced lung cancer based on the latest literature and current clinical experience, mainly focusing on the appropriateness of surgical therapy and emerging data regarding neoadjuvant and adjuvant therapies. CONCLUSIONS Despite the complex decision-making process in managing locally advanced lung cancer, this expert panel agreed on several key recommendations. This document provides guidance for thoracic surgeons and other medical professionals in the optimal management of locally advanced lung cancer based on the most updated evidence and literature.
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Affiliation(s)
- Samuel S Kim
- Canning Thoracic Institute, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
| | - David T Cooke
- Division of General Thoracic Surgery, University of California Davis Health, Sacramento, California
| | - Biniam Kidane
- Section of Thoracic Surgery, CancerCare Manitoba and University of Manitoba, Winnipeg, Manitoba, Canada
| | - Luis F Tapias
- Division of Thoracic Surgery, Mayo Clinic, Rochester, Minnesota
| | - John F Lazar
- Division of Thoracic Surgery, Ascension Saint Thomas Hospital, University of Tennessee Health Science Center, Nashville, Tennessee
| | - Jeremiah W Awori Hayanga
- Department of Cardiothoracic and Vascular Surgery, West Virginia University Medicine, Morgantown, West Virginia
| | - Jyoti D Patel
- Division of Hematology/Oncology, Department of Medicine, Northwestern University, Chicago, Illinois
| | - Joel W Neal
- Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford, California
| | - Mohamed E Abazeed
- Department of Radiation Oncology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
| | - Henning Willers
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Joseph B Shrager
- Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California; Department of Surgery, Veterans Affairs Palo Altos Health Care System, Stanford, California
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Cho SE, Lee Y, Kim JI, Jung KY, Jeong H, Park HW, Lee BI. Comparative crystal structure analysis of the human EP300 and CBP KIX domains. Biochem Biophys Res Commun 2024; 741:151064. [PMID: 39612645 DOI: 10.1016/j.bbrc.2024.151064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 11/23/2024] [Indexed: 12/01/2024]
Abstract
Small-cell lung cancer (SCLC) is highly lethal because the tumors grow and metastasize rapidly. Effective treatments for SCLC are lacking currently. A recent study demonstrated that the E1A binding protein P300 (EP300) KIX domain has pro-tumorigenic activity and is selectively involved in the development and growth of SCLC. These findings suggest the possibility of developing small-molecule inhibitors of EP300 KIX as new targeted therapies for SCLC. In this study, we reported the crystal structure of the human EP300 KIX domain at 2.9 Å resolution except for a flexible loop and C-terminal end. The overall structure was almost identical to that of the cAMP response element-binding protein (CBP) KIX. Nine EP300 KIX residues were different from those of CBP KIX. Among these non-strictly conserved residues, Ala627, which corresponds to Asp647 in CBP KIX, reduces the negative surface potential. Asn581 and Arg613 contributed to the formation of additional hydrogen bonds in the EP300 KIX structure. Further structural analysis revealed that the hydrophobic residues that form the allosteric network in CBP KIX were well conserved in the EP300 KIX structure. This study lays the groundwork for structure-based drug design for SCLC.
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Affiliation(s)
- Sang Eun Cho
- Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do, 10408, Republic of Korea; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea
| | - Yuno Lee
- Drug Information Research Center, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea
| | - Ji-In Kim
- Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea; College of Pharmacy, Chungbuk National University, Cheongju-si, Chungcheongbuk-do, 28160, Republic of Korea
| | - Kwan-Young Jung
- Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea; Department of Medicinal Chemistry and Pharmacology, University of Science & Technology, Daejeon, 34113, Republic of Korea
| | - Hyeongseop Jeong
- Center for Research Equipment, Korea Basic Science Institute, Cheongju-si, Chungcheongbuk-do, 28119, Republic of Korea
| | - Hyun Woo Park
- Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea
| | - Byung Il Lee
- Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do, 10408, Republic of Korea; Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang-si, Gyeonggi-do, 10408, Republic of Korea.
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Nicola A, Adelina M, Porosnicu TM, Oancea C, Marc MS, Barata PI. Comparing Quality of Life and Psychological Changes in Benign and Malignant Lung Resections. Healthcare (Basel) 2024; 13:6. [PMID: 39791613 PMCID: PMC11719650 DOI: 10.3390/healthcare13010006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Revised: 12/18/2024] [Accepted: 12/23/2024] [Indexed: 01/12/2025] Open
Abstract
Background and Objectives: Pulmonary resections are critical interventions for treating various lung pathologies, both benign and malignant. Understanding the impact of these surgeries on patients' Quality of Life (QoL) is essential for optimizing care. This study aims to compare the Health-Related Quality of Life (HRQoL) and psychological well-being in patients who underwent pulmonary resections for benign versus malignant etiologies. Methods: A cross-sectional study was conducted involving 117 patients who underwent pulmonary resection between January 2022 and June 2023. Participants were divided into two groups: 51 patients with benign lung conditions and 66 with malignant lung tumors. HRQoL was assessed using the SF-36 and WHOQOL-BREF questionnaires. Anxiety and depression levels were evaluated using the Hospital Anxiety and Depression Scale (HADS) and the Perceived Stress Scale (PSS-10). Patients were assessed pre- and post-intervention. Results: Patients with malignant etiologies were older (58.7 vs. 54.2 years) and had lower FEV1% predicted (79.1% vs. 82.5%) compared to the benign group. Malignant patients reported significantly lower scores in physical functioning (68.1 vs. 75.4), role-physical (65.0 vs. 72.3), and general health domains of the SF-36 (62.4 vs. 70.2). WHOQOL-BREF scores indicated a lower overall QoL in the malignant group, particularly in the physical health (65.3 vs. 72.1) and psychological domains (68.0 vs. 74.5). HADS scores revealed higher anxiety (9.1 vs. 7.2) and depression levels (8.5 vs. 6.8) among malignant patients. Correlation analyses showed strong associations between lower QoL scores and higher anxiety and depression levels. Conclusions: Pulmonary resections for malignant conditions are associated with a significant decline in HRQoL compared to benign conditions. Patients with malignant etiologies experience higher levels of anxiety and depression, emphasizing that clinicians should integrate specialized mental health services and tailored physical rehabilitation programs for patients undergoing pulmonary resections for malignant lung conditions to address their significantly reduced quality of life and increased psychological distress.
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Affiliation(s)
- Alin Nicola
- Department of Thoracic Surgery, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania;
- Doctoral School, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Mavrea Adelina
- Department of Internal Medicine I, Cardiology Clinic, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Tamara Mirela Porosnicu
- Department of Anesthesia and Intensive Care, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania;
| | - Cristian Oancea
- Center for Research and Innovation in Precision Medicine of Respiratory Diseases, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, Timisoara 300041, Romania; (C.O.); (M.S.M.); (P.I.B.)
| | - Monica Steluta Marc
- Center for Research and Innovation in Precision Medicine of Respiratory Diseases, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, Timisoara 300041, Romania; (C.O.); (M.S.M.); (P.I.B.)
| | - Paula Irina Barata
- Center for Research and Innovation in Precision Medicine of Respiratory Diseases, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, Timisoara 300041, Romania; (C.O.); (M.S.M.); (P.I.B.)
- Department of Physiology, Faculty of Medicine, “Vasile Goldis” Western University of Arad, 310025 Arad, Romania
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Helal AA, Kamal IH, Osman A, Youssef M, Ibrahim AK. The prevalence and clinical significance of EGFR mutations in non-small cell lung cancer patients in Egypt: a screening study. J Egypt Natl Canc Inst 2024; 36:39. [PMID: 39710832 DOI: 10.1186/s43046-024-00251-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 11/16/2024] [Indexed: 12/24/2024] Open
Abstract
BACKGROUND Lung cancer is a form of cancer that is responsible for the largest incidence of deaths attributed to cancer worldwide. Non-small cell lung cancer (NSCLC) is the most prevalent of all the subtypes of the disease. Treatment with tyrosine kinase inhibitors (TKI) may help some people who have been diagnosed with non-small cell lung cancer. The presence of actionable mutations in the epidermal growth factor receptor (EGFR) gene is a key predictor of how a patient will respond to a TKI. Thus, the frequency of identification of mutations in EGFR gene in patients with NSCLC can facilitate personalized treatment. OBJECTIVE The objective of this study was to screen for mutations in the EGFR gene and to investigate whether there is a correlation between the screened mutations and various clinical and pathological factors, such as gender, smoking history, and age, in tissue samples from patients with NSCLC. METHODS The study comprised 333 NSCLC tissue samples from 230 males and 103 females with an average age of 50 years. Exons 18-21 of the EGFR gene have been examined using real-time PCR. Using SPSS, correlations between clinical and demographic variables were examined, and EGFR mutation and clinical features associations were studied. RESULTS The study's findings revealed that the incidence rate of EGFR mutation was 24.32% (81/333), with partial deletion of exon 19 (19-Del) and a point mutation of L858R in exon 21 accounting for 66.67% (P < 0.001) and 28.40% (P < 0.001) of the mutant cases, respectively. Patients who had the T790M mutation represent 4.94% (P = 0.004) of total number of patients. Females harbored EGFR mutations (54.32%) with higher frequency than men (45.68%) (P < 0.001), while nonsmokers had EGFR mutations (70.37%) more frequently than current smokers (29.63%) (P < 0.001). CONCLUSION The screening study conducted in Egypt reported that the EGFR mutations prevalence was 24.32% among Egyptians with NSCLC. The study also found a slight gender bias, with females having an incidence rate of these mutations higher than males. Additionally, nonsmokers had higher rates of mutations in EGFR gene compared to smokers. According to the findings, somatic EGFR mutations can be employed as a diagnostic tool for non-small cell lung cancer in Egypt, and they can be implemented in conjunction with clinical criteria to identify which patients are more likely to respond favorably to TKIs.
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Affiliation(s)
- Asmaa A Helal
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt.
| | - Ibrahim H Kamal
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt
| | - Ahmed Osman
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt
- Biotechnology Program, Institute of Basic and Applied Sciences, Egypt-Japan University of Science and Technology, Alexandria, 21934, Egypt
| | | | - Adel K Ibrahim
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
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40
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Boussios S, Sheriff M, Ovsepian SV. Molecular Biology of Cancer-Interplay of Malignant Cells with Emerging Therapies. Int J Mol Sci 2024; 25:13090. [PMID: 39684799 DOI: 10.3390/ijms252313090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
Cancer is currently one of the leading causes of death worldwide, and according to data from the World Health Organization reported in 2020, it ranks as the second leading cause of death globally, accounting for 10 million fatalities [...].
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Affiliation(s)
- Stergios Boussios
- Faculty of Medicine, Health and Social Care, Canterbury Christ Church University, Canterbury CT1 1QU, UK
- Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, King's College London, Strand, London WC2R 2LS, UK
- Kent Medway Medical School, University of Kent, Canterbury CT2 7LX, UK
- AELIA Organization, 9th Km Thessaloniki-Thermi, 57001 Thessaloniki, Greece
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK
| | - Matin Sheriff
- Department of Urology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK
| | - Saak V Ovsepian
- Faculty of Engineering and Science, University of Greenwich London, Chatham Maritime, Gillingham ME4 4AG, UK
- Faculty of Medicine, Tbilisi State University, Tbilisi 0179, Georgia
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Wei Q, Lin J, Lin Z, Yu N, Wu Y, Tan X, Xue D. GOLPH3 inhibition overcomes cisplatin resistance by restoring the glutathione/reactive oxygen species balance in the A549 non‑small cell lung cancer cell line. Oncol Rep 2024; 52:170. [PMID: 39422070 PMCID: PMC11526445 DOI: 10.3892/or.2024.8829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Accepted: 07/17/2024] [Indexed: 10/19/2024] Open
Abstract
Cisplatin resistance is common in non‑small cell lung cancer (NSCLC); however, the molecular mechanisms remain unclear. The present study aimed to identify a new function of Golgi phosphoprotein 3 (GOLPH3) in NSCLC‑associated cisplatin resistance. Using A549 human NSCLC cells and the cisplatin‑resistant variant, stable cell lines with GOLPH3 knockdown or overexpression were established using lentiviral vectors. Through Cell Counting Kit‑8 and EdU assays, it was revealed that knockdown of GOLPH3 significantly enhanced cisplatin sensitivity in NSCLC cells. Specifically, flow cytometric analysis showed that GOLPH3 knockdown promoted apoptosis and G2‑phase cell cycle arrest in A549 cells. Mechanistically, intracellular reactive oxygen species (ROS) and glutathione (GSH) levels were measured using assay kits, and it was demonstrated that GOLPH3 knockdown decreased intracellular GSH levels, and further attenuated intracellular cisplatin efflux and GSH/ROS imbalance. In addition, tumor‑sphere formation assays verified that GOLPH3 knockdown mitigated the stem cell‑like phenotype of NSCLC cells. In conclusion, the present findings indicated the relevance of GOLPH3 in NSCLC‑associated cisplatin resistance, and thus targeting GOLPH3 may be developed into a combination therapy to overcome cisplatin resistance.
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Affiliation(s)
- Qiongying Wei
- Department of Pulmonary and Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
- Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Jinquan Lin
- Department of Trauma Center and Emergency Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
- Department of Trauma Center and Emergency Surgery, National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350212, P.R. China
| | - Zhuangbin Lin
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Nanding Yu
- Department of Pulmonary and Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
- Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Yingxiao Wu
- Department of Pulmonary and Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
- Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Xuexue Tan
- Department of Pulmonary and Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
- Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Dan Xue
- Department of Pulmonary and Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
- Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
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Bai B, An X, Qu Q, Liu X, Liu Y, Wei L. The clinical features and prognostic implications of the co-mutated TP53 gene in advanced non-small cell lung cancer. Clin Transl Oncol 2024; 26:3236-3245. [PMID: 38872053 DOI: 10.1007/s12094-024-03533-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 05/18/2024] [Indexed: 06/15/2024]
Abstract
BACKGROUND TP53 is a frequently mutated oncogene within non-small cell lung cancer (NSCLC). However, the clinical and prognostic significance of co-mutations in TP53 in patients with advanced NSCLC has not been fully elucidated. METHODS A total of 174 patients with advanced NSCLC were enrolled in this study. All patients were subjected to sequencing analysis of tumor-related genes and information such as PD-L1 expression, TMB, and co-mutation changes were collected. Patients were categorized into TP53 mutant and TP53 wild-type groups according to their TP53 mutation status and then statistically analyzed. RESULTS TP53 mutations were the most common among all patients, accounting for 56.32%, followed by epidermal growth factor receptor mutations at 48.27%. The most common mutation sites in the TP53 mutation group were exons 5-8.TP53 mutations were significantly associated with PD-L1 and TMB levels. Univariate Cox analysis showed that gender and EGFR mutation affected the prognosis of TP53-mutated NSCLC patients, and multivariate Cox regression analysis identified EGFR mutation as an independent risk factor. The OS of NSCLC patients in the TP53 mutation group was significantly shorter than that of the TP53wt group. Survival curves in the TP53/EGFR combined mutation group showed that patients with combined EGFR mutation had a lower survival rate. DISCUSSION TP53 mutations are associated with different clinical indicators and have important implications in clinical treatment. TP53 is a poor prognostic factor for NSCLC patients, and TP53/EGFR co-mutation will affect the survival time of patients. TP53/EGFR co-mutation may be a new prognostic marker for NSCLC.
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Affiliation(s)
- Bing Bai
- Tai'an City Central Hospital (Tai'an Central Hospital Affiliated to Qingdao University, Mount Taishan Medical Center), Tai'an, 271000, Shandong, China
| | - Xia An
- Department of Respiratory Medicine, The Second Affiliated Hospital of Shandong First Medical University, No. 336 Taishan Street, Taishan District, Tai'an, 271000, Shandong, China
| | - Qinghui Qu
- Yutai County People's Hospital, Jining, 272300, Shandong, China
| | - Xin Liu
- Department of Respiratory Medicine, The Second Affiliated Hospital of Shandong First Medical University, No. 336 Taishan Street, Taishan District, Tai'an, 271000, Shandong, China.
| | - Yuanyuan Liu
- Department of Respiratory Medicine, The Second Affiliated Hospital of Shandong First Medical University, No. 336 Taishan Street, Taishan District, Tai'an, 271000, Shandong, China
| | - Li Wei
- Department of Respiratory Medicine, The Second Affiliated Hospital of Shandong First Medical University, No. 336 Taishan Street, Taishan District, Tai'an, 271000, Shandong, China
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Li Y, Wang B, Fei S, Qin Y. Predictive value of direct bilirubin and total bile acid in lung adenocarcinoma patients treated with EGFR-TKIs. BMC Pulm Med 2024; 24:583. [PMID: 39580432 PMCID: PMC11585954 DOI: 10.1186/s12890-024-03367-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Accepted: 10/25/2024] [Indexed: 11/25/2024] Open
Abstract
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have been the standard treatment for patients with sensitizing EGFR mutation. However, almost all patients eventually acquire resistance to EGFR-TKIs. Therefore, easily available parameters to estimate the outcome of lung adenocarcinoma patients treated with EGFR-TKIs are in urgent need. Lung adenocarcinoma patients harbored EGFR sensitive mutant and received EGFR-TKIs as first-line or second-line treatment were recruited in the study. X-tile software were utilized to determine the optimal cut-off value of Alkaline phosphatase (ALP), direct bilirubin (DB), total bile acid (TBA), and high-density lipoprotein-cholesterol (HDL-C). The prognostic value of ALP, DB, TBA, and HDL-C for Progression-free survival (PFS) in patients were evaluated by the Kaplan-Meier curve. We applied univariate and multivariate survival analysis to identify the independent predictor for PFS in patients with EGFR-mutant advanced lung adenocarcinoma and received EGFR-TKIs. A total of 131 lung adenocarcinoma patients with a median age of 58 years old were included in the final analysis. Patients with elevated level of DB and HDL-C showed a longer PFS, while high level of ALP and TBA indicated shorter PFS in response to EGFR-TKI treatment. The multivariate survival analyses revealed a significant association of prolonged PFS with increased DB, and decreased TBA. In conclusion, these findings suggest that DB and TBA were significant independent predictors of PFS in EGFR-TKI-treated patients with advanced lung adenocarcinoma.
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Affiliation(s)
- Yuting Li
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Precision Radiation Oncology, Wuhan, China
| | - Bicheng Wang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Precision Radiation Oncology, Wuhan, China
| | - Shihong Fei
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Key Laboratory of Precision Radiation Oncology, Wuhan, China.
| | - You Qin
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Key Laboratory of Precision Radiation Oncology, Wuhan, China.
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Tamtaji Z, Sheikhsagha E, Behnam M, Nabavizadeh F, Shafiee Ardestani M, Rahmati-Dehkordi F, Aschner M, Mirzaei H, Tamtaji OR. Berberine and Lung Cancer: From Pure Form to Its Nanoformulations. Asia Pac J Clin Oncol 2024. [PMID: 39568275 DOI: 10.1111/ajco.14134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 05/31/2024] [Accepted: 10/28/2024] [Indexed: 11/22/2024]
Abstract
Lung cancer is the most fatal cancer worldwide. The etiology of lung cancer has yet to be fully characterized. Smoking and air pollution are several risk factors for lung cancer. Berberine, an isoquinoline alkaloid, is an antihyperglycemic, antidepressant, antioxidative, anti-inflammatory, and anticancer compound. Evidence substantiates that berberine has antitumor effects, exerting its effects by targeting a variety of cellular and molecular processes, such as apoptosis, autophagy, cell cycle arrest, migration, and metastasis. Although the beneficial effects of berberine have been reported, some limitations including low bioavailability and absorption as well as poor aqueous solubility have hindered its clinical application. Nanotechnology and nanodelivery bioformulation approaches may bypass these limitations. In addition, the combination of berberine with other therapies has been shown to result in greater treatment efficacy for lung cancer. Herein, we summarize cellular and molecular pathways that are affected by berberine, its clinical efficacy upon various combinations, and the potential for nanotechnology in lung cancer therapy.
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Affiliation(s)
- Zeinab Tamtaji
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Elham Sheikhsagha
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland
| | - Mohammad Behnam
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Fatemeh Nabavizadeh
- Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran
| | - Mehdi Shafiee Ardestani
- Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran
| | - Fatemeh Rahmati-Dehkordi
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran
- Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Omid R Tamtaji
- Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran
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Morgensztern D, Ready N, Johnson ML, Dowlati A, Choudhury N, Carbone DP, Schaefer E, Arnold SM, Puri S, Piotrowska Z, Hegde A, Chiang AC, Iams W, Tolcher A, Nosaki K, Kozuki T, Li T, Santana-Davila R, Akamatsu H, Murakami H, Yokouchi H, Wang S, Zha J, Li R, Robinson RR, Hingorani P, Jeng EE, Furqan M. A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6-Targeting Antibody-Drug Conjugate, in Patients with Small Cell Lung Cancer. Clin Cancer Res 2024; 30:5042-5052. [PMID: 39287821 PMCID: PMC11565168 DOI: 10.1158/1078-0432.ccr-24-1547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 07/17/2024] [Accepted: 09/13/2024] [Indexed: 09/19/2024]
Abstract
PURPOSE Seizure-related homolog protein 6 (SEZ6) is a novel target expressed in small cell lung cancer (SCLC). ABBV-011, a SEZ6-targeted antibody conjugated to calicheamicin, was evaluated in a phase I study (NCT03639194) in patients with relapsed/refractory SCLC. We report initial outcomes of ABBV-011 monotherapy. PATIENTS AND METHODS ABBV-011 was administered intravenously once every 3 weeks during dose escalation (0.3-2 mg/kg) and expansion. Patients with SEZ6-positive tumors (≥25% of tumor cells with ≥1+ staining intensity by IHC) were preselected for expansion. Safety, tolerability, antitumor activity, and pharmacokinetics were evaluated. RESULTS As of August 2022, 99 patients received ABBV-011 monotherapy [dose escalation, n = 36; Japanese dose evaluation, n = 3; dose expansion, n = 60 (1 mg/kg, n = 40)]; the median age was 63 years (range, 41-79 years). Also, 32%, 41%, and 26% of patients received 1, 2, and ≥3 prior therapies, respectively. The maximum tolerated dose was not reached through 2.0 mg/kg. The most common treatment-emergent adverse events were fatigue (50%), nausea (42%), and thrombocytopenia (41%). The most common hepatic treatment-emergent adverse events were increased aspartate aminotransferase (22%), increased γ-glutamyltransferase (21%), and hyperbilirubinemia (17%); two patients experienced veno-occlusive liver disease. The objective response rate was 19% (19/98). In the 1-mg/kg dose-expansion cohort (n = 40), the objective response rate was 25%; the median response duration was 4.2 months (95% confidence interval, 2.6-6.7); and the median progression-free survival was 3.5 months (95% confidence interval, 1.5-4.2). CONCLUSIONS ABBV-011 1.0 mg/kg every 3 weeks monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated patients with relapsed/refractory SCLC. SEZ6 is a promising novel SCLC target and warrants further investigation.
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Affiliation(s)
| | - Neal Ready
- Duke Cancer Institute, Duke University, Durham, North Carolina
| | - Melissa L. Johnson
- Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville, Tennessee
| | - Afshin Dowlati
- University Hospitals Seidman Cancer Center, Cleveland, Ohio
- Case Western Reserve University, Cleveland, Ohio
| | | | - David P. Carbone
- The Ohio State University James Cancer Center and the Pelotonia Institute for Immuno-Oncology, Columbus, Ohio
| | | | | | - Sonam Puri
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Zofia Piotrowska
- Massachusetts General Hospital Cancer Center/Harvard Medical School, Boston, Massachusetts
| | - Aparna Hegde
- University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
| | | | - Wade Iams
- Vanderbilt University Medical Center, Nashville, Tennessee
| | | | - Kaname Nosaki
- National Cancer Center Hospital East, Kashiwa, Japan
| | - Toshiyuki Kozuki
- National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan
| | - Tianhong Li
- University of California, Davis Comprehensive Cancer Center, Sacramento, California
| | | | | | | | - Hiroshi Yokouchi
- National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan
| | - Song Wang
- AbbVie, Inc., North Chicago, Illinois
| | | | - Rui Li
- AbbVie, Inc., North Chicago, Illinois
| | | | | | | | - Muhammad Furqan
- University of Iowa Holden Comprehensive Cancer Center, Iowa City, Iowa
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Añorve Bailon D, Picó-Guzmán J, Cifuentes S, Trejo R, Rodríguez Cid J, Juarez-Vignon Whaley JJ, Heredia Zepeda AA, Gerson R, Camacho-Limas CP, Martínez-Herrera JF, Molina DB, Camarín Sánchez E, Shveid Gerson D. Estimation of the Clinical, Economic, and Social Burden of Stage IV Non-Small Cell Lung Cancer in Mexico. PHARMACOECONOMICS - OPEN 2024; 8:869-885. [PMID: 39107537 PMCID: PMC11499576 DOI: 10.1007/s41669-024-00514-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/18/2024] [Indexed: 10/25/2024]
Abstract
INTRODUCTION Lung cancer continues to be the leading cause of death among cancer patients worldwide. This study aimed to estimate the clinical, economic, and social burdens of stage IV non-small cell lung cancer (NSCLC) in private and public healthcare centers in Mexico, utilizing real-world evidence. METHODS The study population included patients >18 years of age diagnosed with stage IV NSCLC who received cancer treatment at the Centro Médico Nacional Siglo XXI (IMSS), the Centro Médico Nacional "20 de Noviembre" (ISSSTE), the Mexican Institute of Respiratory Diseases (INER), and the Medical Center ABC (American British Cowdray) from 1 January 2019 to 31 December 2020. The analysis included evaluation of epidemiological data, treatment regimens, and clinical outcomes, and emphasized pharmacological and non-pharmacological treatments, including detailed follow-up investigations, as part of comprehensive clinical management. Additionally, the study assessed the social burden through variables such as working-age absenteeism and presenteeism and caregiver productivity loss, as well as economic burden, considering both clinical and social components, with costs adjusted to 2022 Mexican pesos (MXN) values. RESULTS A total of 188 patients with metastatic NSCLC were studied. The main type of NSCLC tumor found in the sample was adenocarcinoma (81%). Treatment regimens included pharmacological treatments (78%), non-pharmacological treatments (25%), and palliative care (24%). Complications were present in 73% of the cohort, while 60% presented adverse events. Clinical management costs of up to MXN1,001,579 per patient in the public sector and MXN2,140,604 in the private sector were reported. It was estimated that working-age patients lose 84-335 days yearly due to absenteeism and presenteeism, while caregivers report a productivity loss equivalent to 13-30 days due to the management of NSCLC patients. These indirect costs of NSCLC contribute to the social burden. A working-age patient with stage IV disease is associated with an average indirect cost of MXN49,731-178,287 in public institutions, while in private institutions, the cost elevates to MXN438,103. CONCLUSIONS This study highlights the substantial clinical, economic, and social burdens of stage IV NSCLC in Mexico, revealing significant disparities between public and private healthcare sectors. It underscores the urgent need for standardized practices and equitable care across all systems.
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Affiliation(s)
| | | | - Sergio Cifuentes
- ISSSTE, Centro Médico Nacional "20 de Noviembre", Ciudad de México, CDMX, México
| | - Rogelio Trejo
- IMSS, Centro Médico Nacional Siglo XXI, Ciudad de México, México
| | - Jeronimo Rodríguez Cid
- Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, México
| | | | | | | | | | - José Fabián Martínez-Herrera
- Centro Médico ABC, Ciudad de México, México
- Universidad Científica del Sur, Cancer Research Networking, Lima, Peru
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Hamada T, Ishikawa H, Rosenzweig MQ, Nishimura N, Sakakibara-Konishi J, Itoh T. Feasibility of a nurse-initiated brief cognitive behavioral strategy intervention program for symptom clusters experienced by patients with advanced non-small cell lung cancer. Asia Pac J Oncol Nurs 2024; 11:100600. [PMID: 39655228 PMCID: PMC11626806 DOI: 10.1016/j.apjon.2024.100600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 09/22/2024] [Indexed: 12/12/2024] Open
Abstract
Objective To assess the feasibility of a nurse-initiated brief cognitive behavioral strategy (CBS) intervention program targeting pain and fatigue symptoms among the pain and fatigue/anorexia symptom clusters experienced by patients with advanced non-small cell lung cancer (NSCLC). Methods In this single-group, pre-post test study, 15 NSCLC outpatients undergoing medical treatment participated. After providing informed consent, participants completed a baseline questionnaire and received a booklet detailing brief cognitive-behavioral techniques (e.g., relaxation, symptom-management strategies), exercise therapy, and related tools. Follow-up calls were made five times over a 10-week period to monitor adherence and assess symptom severity changes. Results Ten participants (66.7%) completed the program. For pain management, 86.7% of participants chose deep breathing as a relaxation technique, and 80.0% used exercise to alleviate fatigue. Median symptom severities decreased from baseline to week 10 as follows: pain (2.00 to 1.00), sadness (1.00 to 0.00), and anxiety (1.00 to 0.50). Conclusions The naurse-initiated brief CBS intervention program is feasible and clinically relevant for patients with advanced NSCLC undergoing standard treatment in Japan.
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Affiliation(s)
- Tamami Hamada
- Department of Nursing, Asahikawa Medical University, Asahikawa, Japan
| | - Hiroko Ishikawa
- Department of Nursing, Hyogo Medical University, Kobe, Japan
| | | | - Naoki Nishimura
- Department of Pulmonary Medicine, Thoracic Center, St. Luke's International Hospital, Tokyo, Japan
| | | | - Toshihiro Itoh
- Department of Nursing, Asahikawa Medical University, Asahikawa, Japan
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Maffeo D, Rina A, Serio VB, Markou A, Powrózek T, Constâncio V, Nunes SP, Jerónimo C, Calvo A, Mari F, Frullanti E, Rosati D, Palmieri M. The Evidence Base for Circulating Tumor DNA-Methylation in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel) 2024; 16:3641. [PMID: 39518079 PMCID: PMC11544801 DOI: 10.3390/cancers16213641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 10/17/2024] [Accepted: 10/25/2024] [Indexed: 11/16/2024] Open
Abstract
Background: Non-Small Cell Lung Cancer (NSCLC) remains a challenging disease to manage with effectiveness. Early detection and precise monitoring are crucial for improving patient outcomes. Circulating tumor DNA (ctDNA) offers a non-invasive cancer detection and monitoring method. Emerging biomarkers, such as ctDNA methylation, have shown promise in enhancing diagnostic accuracy and prognostic assessment in NSCLC. In this review, we examined the current evidence regarding ctDNA methylation's role in NSCLC detection through a systematic review of the existing literature and meta-analysis. Methods: We systematically searched PubMed, Medline, Embase, and Web of Science databases up to 26 June 2024 for studies on the role of ctDNA methylation analysis in NSCLC patients. We included studies from 2010 to 2024 on NSCLC patients. We excluded case reports, non-English articles, studies on cell lines or artificial samples, those without cfDNA detection, prognostic studies, and studies with non-extractable data or mixed cancer types. Funnel plots were visually examined for potential publication bias, with a p value < 0.05 indicating bias. Meta-analysis was conducted using R packages (meta, forestplot, and mada). Combined sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive and negative predictive values, diagnostic odds ratio (DOR), and 95% confidence intervals (95% CI) were calculated. A summary receiver operating characteristic curve (SROC) and area under the curve (AUC) with related Standard Error (SE) were used to evaluate the overall diagnostic performance. Additionally, RASSF1A, APC, SOX17, SEPT9, and RARβ2 were analyzed, since their methylation was assessed in two or more studies. Results: From 38 candidate papers, we finally identified 12 studies, including 472 NSCLC patients. The pooled sensitivity was 0.62 (0.47-0.77) and the specificity was 0.90 (0.85-0.94). The diagnostic odds ratio was 15.6 (95% CI 9.36-26.09) and the area under the curve was 0.249 (SE = 0.138). The positive and negative predictive values were 5.38 (95% CI 3.89-7.44) and 0.34 (95% CI 0.22-0.54), respectively. For single genes, the specificity reached 0.83~0.96, except for RARβ2, but the sensitivity was relatively low for each gene. Significant heterogeneity across the included studies, the potential publication bias for specificity (p = 0.0231), and the need to validate the clinical utility of ctDNA methylation for monitoring treatment response and predicting outcomes in NSCLC patients represent the main limitations of this study. Conclusions: These results provide evidence of the significant potential of ctDNA methylation as a valuable biomarker for improving the diagnosis of NSCLC, advocating for its integration into clinical practice to enhance patient management.
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Affiliation(s)
- Debora Maffeo
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy; (D.M.); (A.R.); (V.B.S.); (D.R.); (M.P.)
- Cancer Genomics and Systems Biology Lab, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
| | - Angela Rina
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy; (D.M.); (A.R.); (V.B.S.); (D.R.); (M.P.)
- UOC Laboratorio di Assistenza e Ricerca Traslazionale, Dipartimento di Terapie cellulari, Ematologia e Medicina di Laboratorio, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy;
| | - Viola Bianca Serio
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy; (D.M.); (A.R.); (V.B.S.); (D.R.); (M.P.)
- Cancer Genomics and Systems Biology Lab, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
| | - Athina Markou
- Lab of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15772 Athens, Greece;
| | - Tomasz Powrózek
- Department of Human Physiology, University of Lublin, 20080 Lublin, Poland;
| | - Vera Constâncio
- Cancer Biology and Epigenetics Group, Research Center (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal; (V.C.); (S.P.N.); (C.J.)
| | - Sandra P. Nunes
- Cancer Biology and Epigenetics Group, Research Center (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal; (V.C.); (S.P.N.); (C.J.)
| | - Carmen Jerónimo
- Cancer Biology and Epigenetics Group, Research Center (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal; (V.C.); (S.P.N.); (C.J.)
- Department of Pathology and Molecular Immunology, ICBAS-School of Medicine & Biomedical Sciences, University of Porto, 4099-002 Porto, Portugal
| | - Alfonso Calvo
- Program in Solid Tumors, CIMA, Cancer Center Clínica Universidad de Navarra (CCUN), Instituto de Investigación Sanitaria de Navarra (IDISNA), Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, 31008 Pamplona, Spain;
- CIBERONC, ISCIII, 28029 Madrid, Spain
| | - Francesca Mari
- UOC Laboratorio di Assistenza e Ricerca Traslazionale, Dipartimento di Terapie cellulari, Ematologia e Medicina di Laboratorio, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy;
| | - Elisa Frullanti
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy; (D.M.); (A.R.); (V.B.S.); (D.R.); (M.P.)
- Cancer Genomics and Systems Biology Lab, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
| | - Diletta Rosati
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy; (D.M.); (A.R.); (V.B.S.); (D.R.); (M.P.)
- Cancer Genomics and Systems Biology Lab, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
| | - Maria Palmieri
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy; (D.M.); (A.R.); (V.B.S.); (D.R.); (M.P.)
- Cancer Genomics and Systems Biology Lab, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
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Anvar MT, Rashidan K, Arsam N, Rasouli-Saravani A, Yadegari H, Ahmadi A, Asgari Z, Vanan AG, Ghorbaninezhad F, Tahmasebi S. Th17 cell function in cancers: immunosuppressive agents or anti-tumor allies? Cancer Cell Int 2024; 24:355. [PMID: 39465401 PMCID: PMC11514949 DOI: 10.1186/s12935-024-03525-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 10/08/2024] [Indexed: 10/29/2024] Open
Abstract
T helper (Th) 17 cells, a distinct subset of Th lymphocytes, are known for their prominent interleukin (IL)-17 production and other pro-inflammatory cytokines. These cells exhibit remarkable plasticity, allowing them to exhibit different phenotypes in the cancer microenvironment. This adaptability enables Th17 cells to promote tumor progression by immunosuppressive activities and angiogenesis, but also mediate anti-tumor immune responses through employing immune cells in tumor setting or even by directly converting toward Th1 phenotype and producing interferon-gamma (IFN-γ). This dual role of Th17 cells in cancer makes it a double-edged sword in encountering cancer. In this review, we aim to elucidate the complexities of Th17 cell function in cancer by summarizing recent studies and, ultimately, to design novel therapeutic strategies, especially targeting Th17 cells in the tumor milieu, which could pave the way for more effective cancer treatments.
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Affiliation(s)
- Milad Taghizadeh Anvar
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kimiya Rashidan
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nima Arsam
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ashkan Rasouli-Saravani
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamidreza Yadegari
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Ahmadi
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zeynab Asgari
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmad Ghorbani Vanan
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Farid Ghorbaninezhad
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Safa Tahmasebi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Zhang S, Liu Y, Liu K, Hu X, Gu X. A review of current developments in RNA modifications in lung cancer. Cancer Cell Int 2024; 24:347. [PMID: 39456034 PMCID: PMC11515118 DOI: 10.1186/s12935-024-03528-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 10/10/2024] [Indexed: 10/28/2024] Open
Abstract
Lung cancer has the highest incidence and mortality rates worldwide and is the primary cause of cancer-related death. Despite the rapid development of diagnostic methods and targeted drugs in recent years, many lung cancer patients do not benefit from effective therapies. The emergence of drug resistance has led to a reduction in the therapeutic effectiveness of targeted drugs, highlighting a crucial need to explore novel therapeutic targets. Many studies have found that epigenetic plays an important role in the occurrence of lung cancer. This review describes the biological function of epigenetic RNA modifications, such as m6A, m5C, m7G, and m1A, and recent advancements in their role in the development, progression, and prognosis of lung cancer. This review aims to provide new guidance for the treatment of lung cancer.
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Affiliation(s)
- Shujun Zhang
- Department of Infectious Diseases, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471000, Henan, China
| | - Yafeng Liu
- Department of Infectious Diseases, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471000, Henan, China
| | - Kaijie Liu
- Department of Infectious Diseases, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471000, Henan, China
| | - Xinjun Hu
- Department of Infectious Diseases, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471000, Henan, China.
- Henan Medical Key Laboratory of Gastrointestinal Microecology and Hepatology, Luoyang, 471000, China.
| | - Xinyu Gu
- Department of Oncology, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Jianxi District, No. 24 Jinghua Road, Luoyang, 471000, Henan, China.
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