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Bernardez B, Higuera O, Martinez-Callejo V, Cardeña-Gutiérrez A, Marcos Rodríguez JA, Santaballa Bertrán A, Majem M, Moreno-Martínez ME. Sex and gender differences in cancer pathogenesis and pharmacology. Clin Transl Oncol 2025:10.1007/s12094-025-03894-1. [PMID: 40164824 DOI: 10.1007/s12094-025-03894-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 02/27/2025] [Indexed: 04/02/2025]
Abstract
Sex and gender may influence the epidemiology, pathogenesis, and prognosis of cancer. This narrative review describes sex and gender differences in the epidemiology and pathogenesis of cancer, and how such differences may impact the pharmacodynamics and pharmacokinetics of cancer treatment. For most types of cancer unrelated to reproductive function, incidence is higher in males than in females, except for gallbladder and thyroid cancers, which are much more common in women. Cancer mortality is higher in men than women; women account for a larger proportion of survivors. These differences may be related to biological differences in pathogenesis or differences in behaviors relating to cancer risk or detection. The pharmacokinetics and pharmacodynamics of cancer therapies also differ between sexes due to differences in body composition, physiology, and receptor expression. Overall, sex and gender are essential variables to be considered in research and clinical practice, influencing diagnosis, subtyping (biomarkers), prognostication, treatment, and dosage.
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Affiliation(s)
- Beatriz Bernardez
- Departament of Medicine and Pharmacology Group, University of Santiago de Compostela, Santiago de Compostela, Spain
- Oncology Pharmacy Unit, Pharmacy Service, University Clinic Hospital of Santiago de Compostela, Santiago de Compostela, Spain
- Santiago de Compostela Research Institute (IDIS), Santiago de Compostela, Spain
| | - Oliver Higuera
- Department of Medical Oncology, La Paz University Hospital, Madrid, Spain
| | - Virginia Martinez-Callejo
- Oncology Pharmacy Unit, Pharmacy Service, Marqués de Valdecilla University Hospital, Avda Marqués de Valdecilla, S/N 39008, Santander, Spain.
| | - Ana Cardeña-Gutiérrez
- Department of Medical Oncology, Nuestra Señora de Candelaria University Hospital, Carretera General del Rosario, 145, 38010, Santa Cruz de Tenerife, Spain.
| | | | | | - Margarita Majem
- Department of Medical Oncology, Santa Creu i Sant Pau Hospital, IIB Sant Pau, Barcelona, Spain
| | - Maria-Estela Moreno-Martínez
- Pharmacy Department, Santa Creu i Sant Pau Hospital, IIB Sant Pau, Barcelona, Spain
- Blanquerna School of Health Sciences, University Ramon Llull, Barcelona, Spain
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Trojnar A, Domagała-Kulawik J. Current insights into the clinico-pathologic characteristics of lung cancer in women. Expert Rev Respir Med 2025; 19:301-312. [PMID: 40040469 DOI: 10.1080/17476348.2025.2475974] [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: 11/12/2024] [Revised: 01/14/2025] [Accepted: 03/03/2025] [Indexed: 03/06/2025]
Abstract
INTRODUCTION Lung cancer is responsible for premature cancer deaths in women and is the first cause of cancer deaths in women in many countries. The problem of lung cancer in women seems to be underestimated in many aspects, including low participation in clinical trials and screening tests. AREAS COVERED Current research progress has contributed to a better understanding of the issue and makes it possible to describe the problem in a new light. In our paper, the problem of lung cancer in women was discussed in a broad aspect, taking into account women's health, the harmful effects of smoking and the current diagnostic and treatment process. The results of treatment also differ in relation to sex. All these aspects of the diversity of women's lung cancer were presented on the basis of newest and most comprehensive literature. EXPERT OPINION Lung cancer in women is and will remain an important health problem worldwide, which is justified by epidemiological data, basic research and treatment results.
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Affiliation(s)
- Anna Trojnar
- Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, Warsaw, Poland
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I P R, T A B, A M S, A N G, E A B, A B R, V S K. Prognostic value of progesterone receptor expression in non-small cell lung cancer tissue. Ir J Med Sci 2025:10.1007/s11845-025-03917-4. [PMID: 40117033 DOI: 10.1007/s11845-025-03917-4] [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: 08/29/2024] [Accepted: 02/18/2025] [Indexed: 03/23/2025]
Abstract
BACKGROUND Progesterone receptors (PRs) play a role in the regulation of cell proliferation and are expressed in non-small cell lung cancer (NSCLC) tissue. Therefore, they represent a potential target for novel antitumor therapies. A survival analysis of NSCLC patients based on PR expression in tumor tissue may help assess the feasibility of using PR modulators in the treatment of this disease. AIM This study aims to evaluate the prognostic significance of PR expression in NSCLC to determine the potential utility of PR modulators as a therapeutic strategy. METHODS PR expression was assessed in 130 surgically resected NSCLC samples using immunofluorescence analysis combined with flow cytometry. Primary antibodies against PR (NBP2-4638, Novus Biologicals, USA) and secondary antibodies conjugated with DyLight650 (ab98729, Abcam, UK) were used. The percentage of PR-expressing cells was quantified using FlowJo software. Statistical analyses were conducted in GraphPad Prism and RStudio using the "survival" package. The prognostic impact of PR expression in NSCLC tissue was evaluated in the overall patient cohort and after excluding censored events (n = 56) to minimize the influence of confounding factors on survival analysis. RESULTS After excluding censored events and stratifying patients based on the median PR expression level (57%), survival analysis revealed that high PR expression in NSCLC tissue is associated with a poorer prognosis (p = 0.05). Patients with high PR expression (≥ 57%) had a median survival of 12.8 months, whereas those with low PR expression (< 57%) had a median survival of 25.8 months (HR = 1.7). CONCLUSIONS Elevated PR expression in NSCLC tumors is associated with reduced patient survival. These findings suggest that PR modulators may have potential therapeutic value for NSCLC patients with PR-positive tumors.
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Affiliation(s)
- Romanov I P
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia.
| | - Bogush T A
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
| | - Scherbakov A M
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
- Gause Institute of New Antibiotics, Moscow, Russia
| | - Grishanina A N
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
| | - Bogush E A
- Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Ravcheeva A B
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
| | - Kosorukov V S
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
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Vona R, Cittadini C, Ortona E, Matarrese P. Sex Disparity in Cancer: Role of Autophagy and Estrogen Receptors. Cells 2025; 14:273. [PMID: 39996745 PMCID: PMC11854201 DOI: 10.3390/cells14040273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/24/2025] [Accepted: 02/07/2025] [Indexed: 02/26/2025] Open
Abstract
Autophagy, a cellular process essential for maintaining homeostasis, plays a fundamental role in recycling damaged components and in adapting to stress. The dysregulation of autophagy is implicated in numerous human diseases, including cancer, where it exhibits a dual role as both a suppressor and a promoter, depending on the context and the stage of tumor development. The significant sex differences observed in autophagic processes are determined by biological factors, such as genetic makeup and sex hormones. Estrogens, through their interaction with specific receptors, modulate autophagy and influence tumor progression, therapy resistance, and the immune response to tumors. In females, the escape from X inactivation and estrogen signaling may be responsible for the advantages, in terms of lower incidence and longer survival, observed in oncology. Women often show better responses to traditional chemotherapy, while men respond better to immunotherapy. The action of sex hormones on the immune system could contribute to these differences. However, women experience more severe adverse reactions to anticancer drugs. The estrogen/autophagy crosstalk-involved in multiple aspects of the tumor, i.e., development, progression and the response to therapy-deserves an in-depth study, as it could highlight sex-specific mechanisms useful for designing innovative and gender-tailored treatments from the perspective of precision medicine.
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Affiliation(s)
- Rosa Vona
- Center for Gender-Specific Medicine, National Institute of Health, 00161 Rome, Italy; (C.C.); (E.O.)
| | | | | | - Paola Matarrese
- Center for Gender-Specific Medicine, National Institute of Health, 00161 Rome, Italy; (C.C.); (E.O.)
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Zhao S, Chen Z, Liu H, Wang X, Zhang X, Shi H. Maternal nutrition and offspring lung health: sex-specific pathway modulation in fibrosis, metabolism, and immunity. Food Nutr Res 2025; 69:11035. [PMID: 39790857 PMCID: PMC11708518 DOI: 10.29219/fnr.v69.11035] [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: 09/08/2024] [Revised: 10/26/2024] [Accepted: 11/26/2024] [Indexed: 01/12/2025] Open
Abstract
Background Maternal nutrition profoundly influences offspring health, impacting both prenatal and early postnatal development. Previous studies have demonstrated that maternal dietary habits can affect key developmental pathways in the offsprings, including those related to lung function and disease susceptibility. However, the sex-specific impact of a maternal high-salt diet (HSD) on offspring lung injury remains poorly understood. Objective This study aimed to investigate the sex-specific effects of maternal HSD on lung injury in mouse offsprings, focusing on pathways related to fibrosis, metabolism, immunity, and apoptosis. Design Pregnant C57BL/6J mice were subjected to either normal or HSD conditions during gestation. Lung tissues from the male and female offsprings were analyzed using high-throughput RNA sequencing and bioinformatics tools to examine transcriptomic changes. Wet-lab validation, including Masson trichrome staining, immunofluorescence for α-SMA, and qRT-PCR for fibrotic markers (α-SMA, collagen I, Fn1, and TGF-β), was conducted to confirm fibrosis and other injury markers. Lung structure and weight were also evaluated to assess physical alterations due to maternal diet. Results Maternal HSD significantly altered lung transcriptomes in a sex-specific manner. Male offsprings showed increased susceptibility to fibrosis, as confirmed by histological and molecular analyses, including elevated expression of α-SMA, collagen I, Fn1, and TGF-β. In contrast, female offsprings exhibited distinct changes in metabolic and immune pathways. These findings highlight the differential regulation of pulmonary injury mechanisms between male and female offsprings exposed to HSD. Conclusions Maternal HSD induces sex-specific lung injury in offsprings by disrupting critical pathways involved in fibrosis, metabolism, immunity, and apoptosis. The combination of transcriptomic and orthogonal data underscores the need for balanced maternal nutrition during pregnancy to promote long-term respiratory health in offsprings. These results provide new insights into the sex-specific vulnerabilities to lung disease arising from maternal diet.
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Affiliation(s)
- Shuangyi Zhao
- Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhimin Chen
- Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Huina Liu
- Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xinyan Wang
- Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiuru Zhang
- Department of Surgery of Spine and Spinal Cord, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Huirong Shi
- Department of Gynaecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Georgakopoulou VE, Lempesis IG, Trakas N, Sklapani P, He Y, Spandidos DA. Lung cancer and obesity: A contentious relationship (Review). Oncol Rep 2024; 52:158. [PMID: 39497438 PMCID: PMC11462394 DOI: 10.3892/or.2024.8817] [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: 04/08/2024] [Accepted: 09/25/2024] [Indexed: 11/08/2024] Open
Abstract
The global obesity epidemic, attributed to sedentary lifestyles, unhealthy diets, genetics and environmental factors, has led to over 1.9 billion adults being classified as overweight and 650 million living with obesity. Despite advancements in early detection and treatment, lung cancer prognosis remains poor due to late diagnoses and limited therapies. The obesity paradox challenges conventional thinking by suggesting that individuals with obesity and certain diseases, including cancer, may have an improved prognosis compared with their counterparts of a normal weight. This observation has prompted investigations to understand protective mechanisms, including potentially favorable adipokine secretion and metabolic reserves that contribute to tolerating cancer treatments. However, understanding the association between obesity and lung cancer is complex. While smoking is the primary risk factor of lung cancer, obesity may independently impact lung cancer risk, particularly in non‑smokers. Adipose tissue dysfunction, including low‑grade chronic inflammation, and hormonal changes contribute to lung cancer development and progression. Obesity‑related factors may also influence treatment responses and survival outcomes in patients with lung cancer. The impact of obesity on treatment modalities such as chemotherapy, radiotherapy and surgery is still under investigation. Challenges in managing patients with obesity and cancer include increased surgical complexity, higher rates of postoperative complications and limited treatment options due to comorbidities. Targeted interventions aimed at reducing obesity prevalence and promoting healthy lifestyles are crucial for lung cancer prevention. The impact of obesity on lung cancer is multifaceted and requires further research to elucidate the underlying mechanisms and develop personalized interventions for prevention and treatment.
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Affiliation(s)
| | - Ioannis G. Lempesis
- Medical Chronobiology Program, Division of Sleep Medicine and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Nikolaos Trakas
- Department of Biochemistry, Sismanogleio Hospital, Athens 15126, Greece
| | - Pagona Sklapani
- Department of Biochemistry, Sismanogleio Hospital, Athens 15126, Greece
| | - Yutong He
- Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050010, P.R. China
| | - Demetrios A. Spandidos
- Laboratory of Clinical Virology, School of Medicine, University of Crete, Heraklion 71003, Greece
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Islam MR, Siddiqua SM, Rabbani G, Ayub SBA, Islam R, Saha B, Khatun N, Shahriar MH, Chowdhury MRK, Alif SM, Karim MN. Exploring sex difference in the risk factors and prognosis of inoperable lung cancer. Cancer Treat Res Commun 2024; 41:100848. [PMID: 39490241 DOI: 10.1016/j.ctarc.2024.100848] [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: 08/11/2024] [Revised: 10/08/2024] [Accepted: 10/15/2024] [Indexed: 11/05/2024]
Abstract
BACKGROUND Lung cancer remains a leading cause of cancer-related deaths globally, with increasing incidence among females. Sex differences in lung cancer risk and outcomes are influenced by various factors, including biological characteristics. In Bangladesh, where lung cancer mortality rates are high, patients often present at advanced stages. However, real-time data on sex-specific survival outcomes for inoperable lung cancer in Bangladesh is lacking. METHODS This retrospective study analyzed patients with inoperable lung cancer at the National Institute of Cancer Research and Hospital in Dhaka, Bangladesh, from 2018 to 2019. Patient demographics and clinical parameters were assessed, with survival tracked until June 2020. Statistical analyses included descriptive statistics, Chi-square tests, t-tests, Kaplan-Meier curves, and multivariable Cox regression models. RESULTS Females were diagnosed at a younger age (55.3 ± 12.7 vs 60.5 ± 10.2 years, p < 0.001) and had higher comorbidity rates (36.2 %, p = 0.004). Males had higher smoking rates, while females used more smokeless tobacco. Adenocarcinoma was more prevalent in females (47.2 %) and squamous cell carcinoma in males (42.7 %). After adjusting for various factors, females showed a significant survival advantage (median 16 vs 12 months), particularly in adenocarcinoma (HR: 0.64, 95 %CI:0.46-0.90, p = 0.01) and squamous cell carcinoma (HR: 0.52, 95 %CI:0.32-0.85, p = 0.009). Females also demonstrated better survival when receiving supportive care, chemotherapy, or radiotherapy alone but not in combined therapy. Older males (>70), illiterate, smokers, and those with comorbidities had a poor prognosis compared to females. CONCLUSION This study reveals significant sex-based differences in inoperable lung cancer patients in Bangladesh. Despite earlier diagnosis and higher comorbidities, females demonstrated better survival rates, particularly in adenocarcinoma and squamous cell carcinoma. These findings highlight the need for sex-specific approaches in lung cancer management to improve patient outcomes.
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Affiliation(s)
- Muhammad Rafiqul Islam
- Department of Medical Oncology, National Institute of Cancer Research and Hospital, Dhaka, Bangladesh.
| | | | - Golam Rabbani
- School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
| | - Salman Bashar Al Ayub
- Department of Medical Oncology, National Institute of Cancer Research and Hospital, Dhaka, Bangladesh
| | - Rashedul Islam
- Department of Medical Oncology, National Institute of Cancer Research and Hospital, Dhaka, Bangladesh
| | - Beauty Saha
- Department of Radiotherapy, Mymensingh Medical college & Hospital, Bangladesh
| | - Nazrina Khatun
- Department of Medical Oncology, National Institute of Cancer Research and Hospital, Dhaka, Bangladesh
| | | | | | - Sheikh M Alif
- School of Population and Global Health, The University of Melbourne, Melbourne, Australia; School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
| | - Md Nazmul Karim
- School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
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Zhang S, Zhang X, Huang W, Jiang G, Mo Y, Wei L, Fan P, Chen M, Jiang W. NUSAP1 is Upregulated by Estrogen to Promote Lung Adenocarcinoma Growth and Serves as a Therapeutic Target. Int J Biol Sci 2024; 20:5375-5395. [PMID: 39430250 PMCID: PMC11489181 DOI: 10.7150/ijbs.100188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 09/17/2024] [Indexed: 10/22/2024] Open
Abstract
Nucleolar and spindle-associated protein 1 (NUSAP1), a microtubule-associated protein, has been recently identified to exhibit aberrant expression patterns that correlate with malignant tumorigenesis and progression across various cancer types. However, the specific regulatory mechanisms and potential targeting therapies of NUSAP1 in lung adenocarcinoma (LUAD) remain largely elusive. In this study, by conducting bioinformatics analyses as well as in vitro and in vivo experiments, we identified that NUSAP1 was significantly upregulated in LUAD, with a notable correlation with poorer overall survival, higher scores for immunogenicity and immune infiltration, as well as increased sensitivity to conventional chemotherapeutic drugs such as paclitaxel, docetaxel and vinorelbine in LUAD. Functionally, NUSAP1 overexpression significantly promoted LUAD cell proliferation, while its knockdown markedly suppressed this process. Interestingly, our results revealed that NUSAP1 upregulation was mediated by estrogen via ERβ activation. Furthermore, we identified entinostat as a novel inhibitor of NUSAP1. Pharmacological targeting ERβ/NUSAP1 axis with fulvestrant (ERβ antagonist) or entinostat (novel NUSAP1 inhibitor) significantly reduced LUAD growth both in vitro and in vivo, which may represent effective alternative therapeutic strategies for patients with LUAD.
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Affiliation(s)
- Shaoping Zhang
- Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China
- Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China
| | - Xiaozhen Zhang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Wenjian Huang
- Department of Breast Surgery, the Sixth Affiliated Hospital of South China University of Technology, the Sixth Clinical College of South China University of Technology, Foshan 528225, China
| | - Ganling Jiang
- Department of pharmacy, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510145, China
| | - Yuanxin Mo
- Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Liuxia Wei
- Department of Medical Oncology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530000, China
| | - Pingming Fan
- Department of Breast Surgery, the First Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan, China
| | - Maojian Chen
- Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Wei Jiang
- Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China
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Le H, Simons CCJM, van den Brandt PA. The association between height and risk of lung cancer subtypes in men and women in the Netherlands Cohort Study. Cancer Epidemiol 2024; 92:102613. [PMID: 39024861 DOI: 10.1016/j.canep.2024.102613] [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: 03/18/2024] [Revised: 06/26/2024] [Accepted: 07/04/2024] [Indexed: 07/20/2024]
Abstract
OBJECTIVES Previous studies found no or weak positive associations between height and lung cancer (LC) risk, with differences between sexes. Few studies stratified the association by smoking status and LC subtype. This prospective study investigated the association between height and risks of overall LC and LC subtypes (i.e., adenocarcinoma, squamous cell carcinoma, small cell carcinoma, large cell carcinoma) in Dutch men and women, with comprehensive adjustment for smoking, and stratified by smoking status. MATERIALS AND METHODS Data originate from 120,852 Dutch participants aged 55-69 in 1986 in the Netherlands Cohort Study. Self-reported height and potential confounders were collected at baseline. After 20.3 years of follow-up, 3318 LC cases (2765 men; 553 women) and 4314 subcohort members were included in the multivariable Cox regression analysis. RESULTS There were no significant associations between height and risks of overall LC and LC subtypes in men and women, except for an increased adenocarcinoma risk in taller women (HRquartile4 vs quartile1=1.62, 95% CI: 1.02-2.55, Ptrend=0.031). This positive association was borderline statistically significant in female current smokers only when stratifying on smoking status. No interaction by smoking status was shown in women for any LC risk. In men, smoking modified the association between height and risks of overall LC, large cell and squamous cell carcinoma, with the p-values for interaction of 0.037, 0.007 and 0.050, respectively. CONCLUSION Positive associations between height and LC subtypes were predominantly seen in smokers. Further studies should focus on LC subtypes and stratify the association by smoking status.
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Affiliation(s)
- Huyen Le
- Department of Epidemiology, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Colinda C J M Simons
- Department of Epidemiology, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Piet A van den Brandt
- Department of Epidemiology, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, the Netherlands; Department of Epidemiology, CAPHRI - School for Public Health and Primary Care, Maastricht University Medical Centre+, Maastricht, the Netherlands.
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Barretto AJB, Orda MA, Tsai PW, Tayo LL. Analysis of Modular Hub Genes and Therapeutic Targets across Stages of Non-Small Cell Lung Cancer Transcriptome. Genes (Basel) 2024; 15:1248. [PMID: 39457373 PMCID: PMC11507033 DOI: 10.3390/genes15101248] [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: 08/10/2024] [Revised: 09/07/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024] Open
Abstract
Non-small cell lung cancer (NSCLC), representing 85% of lung cancer cases, is characterized by its heterogeneity and progression through distinct stages. This study applied Weighted Gene Co-expression Network Analysis (WGCNA) to explore the molecular mechanisms of NSCLC and identify potential therapeutic targets. Gene expression data from the GEO database were analyzed across four NSCLC stages (NSCLC1, NSCLC2, NSCLC3, and NSCLC4), with the NSCLC2 dataset selected as the reference for module preservation analysis. WGCNA identified eight highly preserved modules-Cyan, Yellow, Red, Dark Turquoise, Turquoise, White, Purple, and Royal Blue-across datasets, which were enriched in key pathways such as "Cell cycle" and "Pathways in cancer", involving processes like cell division and inflammatory responses. Hub genes, including PLK1, CDK1, and EGFR, emerged as critical regulators of tumor proliferation and immune responses. Estrogen receptor ESR1 was also highlighted, correlating with improved survival outcomes, suggesting its potential as a prognostic marker. Signature-based drug repurposing analysis identified promising therapeutic candidates, including GW-5074, which inhibits RAF and disrupts the EGFR-RAS-RAF-MEK-ERK signaling cascade, and olomoucine, a CDK1 inhibitor. Additional candidates like pinocembrin, which reduces NSCLC cell invasion by modulating epithelial-mesenchymal transition, and citalopram, an SSRI with anti-carcinogenic properties, were also identified. These findings provide valuable insights into the molecular underpinnings of NSCLC and suggest new directions for therapeutic strategies through drug repurposing.
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Affiliation(s)
- Angeli Joy B. Barretto
- School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, Manila City 1002, Philippines; (A.J.B.B.); (M.A.O.)
- School of Graduate Studies, Mapúa University, Manila City 1002, Philippines
| | - Marco A. Orda
- School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, Manila City 1002, Philippines; (A.J.B.B.); (M.A.O.)
- School of Graduate Studies, Mapúa University, Manila City 1002, Philippines
| | - Po-wei Tsai
- Department of Food Science, National Taiwan Ocean University, Keelung 20224, Taiwan;
| | - Lemmuel L. Tayo
- School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, Manila City 1002, Philippines; (A.J.B.B.); (M.A.O.)
- School of Graduate Studies, Mapúa University, Manila City 1002, Philippines
- Department of Biology, School of Health Sciences, Mapúa University, Makati City 1203, Philippines
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Mohd Abas MD, Mohd Asri MF, Yusafawi NAS, Rosman NAZ, Baharudin NAZ, Taher M, Susanti D, Khotib J. Advancements of gene therapy in cancer treatment: A comprehensive review. Pathol Res Pract 2024; 261:155509. [PMID: 39121791 DOI: 10.1016/j.prp.2024.155509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Revised: 07/23/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024]
Abstract
Cancer is the main contributor for mortality in the world. Conventional therapy that available as the treatment options are chemotherapy, radiotherapy and surgery. However, these treatments are hardly cell-specific most of the time. Nowadays, extensive research and investigations are made to develop cell-specific approaches prior to cancer treatment. Some of them are photodynamic therapy, hyperthermia, immunotherapy, stem cell transplantation and targeted therapy. This review article will be focusing on the development of gene therapy in cancer. The objective of gene therapy is to correct specific mutant genes causing the excessive proliferation of the cell that leads to cancer. There are lots of explorations in the approach to modify the gene. The delivery of this therapy plays a big role in its success. If the inserted gene does not find its way to the target, the therapy is considered a failure. Hence, vectors are needed and the common vectors used are viral, non viral or synthetic, polymer based and lipid based vectors. The advancement of gene therapy in cancer treatment will be focussing on the top three cancer cases in the world which are breast, lung and colon cancer. In breast cancer, the discussed therapy are CRISPR/Cas9, siRNA and gene silencing whereas in colon cancer miRNA and suicide gene therapy and in lung cancer, replacement of tumor suppressor gene, CRISPR/Cas9 and miRNA.
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Affiliation(s)
- Muhammad Dhiyauddin Mohd Abas
- Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Jalan Sultan Ahmad Shah, Kuantan, Pahang 25200, Malaysia
| | - Muhammad Fareez Mohd Asri
- Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Jalan Sultan Ahmad Shah, Kuantan, Pahang 25200, Malaysia
| | - Nur Anis Suffiah Yusafawi
- Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Jalan Sultan Ahmad Shah, Kuantan, Pahang 25200, Malaysia
| | - Nur Anis Zahra Rosman
- Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Jalan Sultan Ahmad Shah, Kuantan, Pahang 25200, Malaysia
| | - Nur Arifah Zahidah Baharudin
- Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Jalan Sultan Ahmad Shah, Kuantan, Pahang 25200, Malaysia
| | - Muhammad Taher
- Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Jalan Sultan Ahmad Shah, Kuantan, Pahang 25200, Malaysia.
| | - Deny Susanti
- Department of Chemistry, Faculty of Science, International Islamic University Malaysia, Jalan Sultan Ahmad Shah, Kuantan, Pahang 25200, Malaysia.
| | - Junaidi Khotib
- Department of Pharmacy Practice, Faculty of Pharmacy, Airlangga University, Surabaya 60115, Indonesia.
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12
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Wang Y, Song W, Wang H, Zhu G, Li Y, Wang Z, Li W, Che G. Increased risk of subsequent primary lung cancer among female hormone-related cancer patients: A meta-analysis based on over four million cases. Chin Med J (Engl) 2024; 137:1790-1801. [PMID: 38973242 PMCID: PMC12077558 DOI: 10.1097/cm9.0000000000003132] [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: 11/15/2023] [Indexed: 07/09/2024] Open
Abstract
BACKGROUND The incidence rate of lung cancer in women has significantly increased over the past decade, and previous evidence has indicated a significant relationship between the elevated levels of sex hormones and the risk of lung cancer. Therefore, we hypothesized that female hormone-related cancer (FHRC) patients, including breast, endometrial, cervical, and ovarian cancer patients, may experience a higher risk of developing subsequent lung cancer. This meta-analysis aimed to identify the risk of lung cancer among FHRC patients compared to the general population. METHODS The PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI databases were searched up to May 11, 2022. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were used to identify the risk of subsequent lung cancer after FHRC. Subgroup analyses based on the follow-up time and tumor type were also conducted. RESULTS A total of 58 retrospective cohort studies involving 4,360,723 FHRC participants were included. The pooled results demonstrated that FHRC patients had a significantly increased risk of developing subsequent primary lung cancer (SIR = 1.61, 95% CI: 1.48-1.76, P <0.001). Subgroup analysis revealed an obvious trend of increasing lung cancer risk over time (SIRs for <5 years, ≥5 years, ≥10 years, ≥20 years, and ≥30 years after FHRC: 1.32, 1.59, 1.57, 1.68, and 1.95, respectively). In addition, subgroup analysis stratified by tumor type indicated an increased risk of developing subsequent lung cancer after breast (SIR = 1.25, P <0.001), endometrial (SIR = 1.40, P = 0.019), cervical (SIR = 2.56, P <0.001), and ovarian cancer (SIR = 1.50, P = 0.010). CONCLUSION FHRC patients are more likely to develop lung cancer than the general population. Furthermore, the increased risk of subsequent primary lung cancer is more obvious with a longer survival time and is observed in all types of hormone-related cancer. REGISTRATION International Platform of Registered Systematic Review and Meta-analysis Protocols: No. INPLASY202270044; https://inplasy.com/.
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Affiliation(s)
- Yan Wang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Wenpeng Song
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Haoyu Wang
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Guonian Zhu
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Institute of Respiratory Health, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yangqian Li
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Institute of Respiratory Health, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Zhoufeng Wang
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Networks, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Weimin Li
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Institute of Respiratory Health, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Networks, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Guowei Che
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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13
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Gong S, Li G, Li D, Liu Y, Wu B. The risk for subsequent primary lung cancer after cervical carcinoma: A quantitative analysis based on 864,627 cases. PLoS One 2024; 19:e0305670. [PMID: 38913637 PMCID: PMC11195986 DOI: 10.1371/journal.pone.0305670] [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: 04/22/2024] [Accepted: 06/03/2024] [Indexed: 06/26/2024] Open
Abstract
PURPOSE To compare the risk of developing subsequent primary lung cancer among cervical cancer patients and the general population. METHODS Several databases were searched from inception to April 25, 2023. The standard incidence ratios (SIRs) with 95% confidence intervals (CIs) were combined to identify the risk for second primary lung cancer after cervical carcinoma. Subgroup analyses based on the follow-up period, age, degree of malignancy and source of SIR were conducted. All the statistical analyses were performed with STATA 15.0 software. RESULTS A total of 22 retrospective studies involving 864,627 participants were included. The pooled results demonstrated that cervical cancer patients had a significantly greater risk for lung cancer than did the general population (SIR = 2.63, 95% CI: 2.37-2.91, P<0.001). Furthermore, subgroup analyses stratified by follow-up period (<5 years and ≥5 years), age (≤50 years and <50 years), and degree of malignancy (invasive and in situ) also revealed an increased risk of developing lung cancer among cervical carcinoma patients. CONCLUSION Cervical cancer patients are more likely to develop subsequent primary lung cancer than the general population, regardless of age, follow-up time or degree of malignancy. However, more high-quality prospective studies are still needed to verify our findings.
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Affiliation(s)
- Sheng Gong
- Department of Thoracic Surgery, The Public Health Clinical Center of Chengdu, Chengdu, P.R. China
| | - Gang Li
- Department of Thoracic Surgery, The Public Health Clinical Center of Chengdu, Chengdu, P.R. China
| | - Dan Li
- Department of Thoracic Surgery, The Public Health Clinical Center of Chengdu, Chengdu, P.R. China
| | - Yu Liu
- Department of Thoracic Surgery, The Public Health Clinical Center of Chengdu, Chengdu, P.R. China
| | - Banggui Wu
- Department of Thoracic Surgery, The Public Health Clinical Center of Chengdu, Chengdu, P.R. China
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Bhartiya D, Raouf S, Pansare K, Tripathi A, Tripathi A. Initiation of Cancer: The Journey From Mutations in Somatic Cells to Epigenetic Changes in Tissue-resident VSELs. Stem Cell Rev Rep 2024; 20:857-880. [PMID: 38457060 DOI: 10.1007/s12015-024-10694-7] [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] [Accepted: 02/09/2024] [Indexed: 03/09/2024]
Abstract
Multiple theories exist to explain cancer initiation, although a consensus on this is crucial for developing effective therapies. 'Somatic mutation theory' suggests that mutations in somatic cells during DNA repair initiates cancer but this concept has several attached paradoxes. Research efforts to identify quiescent cancer stem cells (CSCs) that survive therapy and result in metastasis and recurrence have remained futile. In solid cancers, CSCs are suggested to appear during epithelial-mesenchymal transition by the dedifferentiation and reprogramming of epithelial cells. Pluripotent and quiescent very small embryonic-like stem cells (VSELs) exist in multiple tissues but remain elusive owing to their small size and scarce nature. VSELs are developmentally connected to primordial germ cells, undergo rare, asymmetrical cell divisions and are responsible for the regular turnover of cells to maintain tissue homeostasis throughout life. VSELs are directly vulnerable to extrinsic endocrine insults because they express gonadal and gonadotropin hormone receptors. VSELs undergo epigenetic changes due to endocrine insults and transform into CSCs. CSCs exhibit genomic instability and develop mutations due to errors during DNA replication while undergoing excessive proliferation and clonal expansion to form spheroids. Thus tissue-resident VSELs offer a connection between extrinsic insults and variations in cancer incidence reported in various body tissues. To conclude, cancer is indeed a stem cell disease with mutations occurring as a consequence. In addition to immunotherapy, targeting mutations, and Lgr5 + organoids for developing new therapeutics, targeting CSCs (epigenetically altered VSELs) by improving their niche and epigenetic status could serve as a promising strategy to treat cancer.
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Affiliation(s)
- Deepa Bhartiya
- Epigeneres Biotech Pvt Ltd, Todi Mill Compound, Senapati Bapat Marg, Lower Parel, 400013, Mumbai, India.
| | | | - Kshama Pansare
- Epigeneres Biotech Pvt Ltd, Todi Mill Compound, Senapati Bapat Marg, Lower Parel, 400013, Mumbai, India
| | - Anish Tripathi
- Epigeneres Biotech Pvt Ltd, Todi Mill Compound, Senapati Bapat Marg, Lower Parel, 400013, Mumbai, India
| | - Ashish Tripathi
- Epigeneres Biotech Pvt Ltd, Todi Mill Compound, Senapati Bapat Marg, Lower Parel, 400013, Mumbai, India
- 23Ikigai Pte Ltd, 30 Cecil Street, #21-08 Prudentsial Tower, Singapore, 049712, Singapore
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15
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Wang L, Liu B, Shi L, Yan J, Tan W, Li C, Jia B, Wen W, Zhu K, Bai Z, Zhang W, Morawska L, Chen J, Wang J. Diverse Metabolic Effects of Cooking Oil Fume from Four Edible Oils on Human BEAS-2B Cells: Implications for Health Guidelines. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2024; 58:1462-1472. [PMID: 38155590 DOI: 10.1021/acs.est.3c05984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2023]
Abstract
The 2021 WHO guidelines stress the importance of measuring ultrafine particles using particle number concentration (PNC) for health assessments. However, commonly used particle metrics such as aerodynamic diameter and number concentrations do not fully capture the diverse chemical makeup of complex particles. To address this issue, our study used high-throughput mass spectrometry to analyze the properties of cooking oil fumes (COFs) in real time and evaluate their impact on BEAS-2B cell metabolism. Results showed insignificant differences in COF number size distributions between soybean oil and olive oil (peak concentrations of 5.20 × 105/cm3), as well as between corn oil and peanut oil (peak concentrations of 4.35 × 105/cm3). Despite the similar major chemical components among the four COFs, variations in metabolic damage were observed, indicating that the relatively small amount of chemical components of COFs can also influence particle behavior within the respiratory system, thereby impacting biological responses. Additionally, interactions between accompanying gaseous COFs and particles may alter their chemical composition through various mechanisms, introducing additional chemicals and modifying existing proportions. Hence, the chemical composition and gaseous components of COFs hold equal importance to the particle number concentration (PNC) when assessing their impact on human health. The absence of these considerations in the current guidelines underscores a research gap. It is imperative to acknowledge that for a more comprehensive approach to safeguarding public health, guidelines must be regularly updated to reflect new scientific findings and robust epidemiological evidence.
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Affiliation(s)
- Lina Wang
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
- Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China
| | - Bailiang Liu
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
| | - Longbo Shi
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
| | - Jiaqian Yan
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
| | - Wen Tan
- TOFWERK, Nanjing 211800, China
| | - Chunlin Li
- Department of Earth and Planetary Sciences, Weizmann Institute of Science, Rehovot 76100, Israel
| | - Boyue Jia
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
| | - Wen Wen
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
| | - Ke Zhu
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
| | - Zhe Bai
- School of Ecology and Environment, Inner Mongolia University, Hohhot 010021, China
| | - Wei Zhang
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
| | - Lidia Morawska
- International Laboratory for Air Quality and Health (ILAQH), School of Earth of Atmospheric Sciences, Queensland University of Technology, Brisbane 4001, Queensland, Australia
| | - Jianmin Chen
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
- Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China
| | - Jiaxi Wang
- Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200438, China
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Baek MS, Shin H, Gu KM, Jung HI, Kim WY, Jung JW, Shin JW, Jung SY, Kim JY. Sex differences in chronic obstructive pulmonary disease characteristics: the Korea National Health and Nutrition Examination Survey 2007-2018. Korean J Intern Med 2024; 39:137-147. [PMID: 38092558 PMCID: PMC10790036 DOI: 10.3904/kjim.2023.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 07/14/2023] [Accepted: 10/19/2023] [Indexed: 01/17/2024] Open
Abstract
BACKGROUND/AIMS Chronic obstructive pulmonary disease (COPD) is less prevalent in females than males, but it affects mortality in females. There may be sex differences in the clinical characteristics of COPD. METHODS We analyzed the Korea National Health and Nutrition Examination Survey dataset from 2007 to 2018. We compared the clinical characteristics and comorbidities in subjects with COPD according to sex. We adjusted the multivariate logistic regression of lung cancer prevalence according to COPD and sex by age and smoking amount. RESULTS Females with COPD tended to be older than males with COPD (64.1 ± 0.4 yr vs. 62.3 ± 0.2 yr, respectively, p < 0.001). Approximately 89% of males with COPD had a smoking history, while 86% of females with COPD were non-smokers (p < 0.001). Household income was lower (p < 0.001) and asthma and overall malignancy were more prevalent in females with COPD than males with COPD (25.5 vs. 11.6%, respectively, p < 0.001; (6.3 vs. 5.4%, respectively, p < 0.001). However, lung cancer was more common in males with COPD than females with COPD (0.9 vs. 0.1%, respectively, p < 0.001). Lung cancer prevalence increased in males with moderate COPD compared to subjects without COPD (OR, 4.409; 95% CI, 1.741-9.419). CONCLUSION Females with COPD had a lower smoking rate, household income, and lung cancer prevalence than males with COPD. More active COPD screening is needed for women of low socioeconomic status, even if they do not smoke.
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Affiliation(s)
- Moon Seong Baek
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | - Haegwang Shin
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | - Kang-Mo Gu
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | - Hae In Jung
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | - Won Young Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | - Jae-Woo Jung
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | - Jong-Wook Shin
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | | | - Jae-Yeol Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
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Rodriguez-Lara V, Soca-Chafre G, Avila-Costa MR, Whaley JJJV, Rodriguez-Cid JR, Ordoñez-Librado JL, Rodriguez-Maldonado E, Heredia-Jara NA. Role of sex and sex hormones in PD-L1 expression in NSCLC: clinical and therapeutic implications. Front Oncol 2023; 13:1210297. [PMID: 37941543 PMCID: PMC10628781 DOI: 10.3389/fonc.2023.1210297] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 09/28/2023] [Indexed: 11/10/2023] Open
Abstract
Currently, immunotherapy based on PD-1/PD-L1 pathway blockade has improved survival of non-small cell lung cancer (NSCLC) patients. However, differential responses have been observed by sex, where men appear to respond better than women. Additionally, adverse effects of immunotherapy are mainly observed in women. Studies in some types of hormone-dependent cancer have revealed a role of sex hormones in anti-tumor response, tumor microenvironment and immune evasion. Estrogens mainly promote immune tolerance regulating T-cell function and modifying tumor microenvironment, while androgens attenuate anti-tumor immune responses. The precise mechanism by which sex and sex hormones may modulate immune response to tumor, modify PD-L1 expression in cancer cells and promote immune escape in NSCLC is still unclear, but current data show how sexual differences affect immune therapy response and prognosis. This review provides update information regarding anti-PD-1/PD-L immunotherapeutic efficacy in NSCLC by sex, analyzing potential roles for sex hormones on PD-L1 expression, and discussing a plausible of sex and sex hormones as predictive response factors to immunotherapy.
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Affiliation(s)
- Vianey Rodriguez-Lara
- Department of Cell and Tissue Biology, Faculty of Medicine, UNAM, Mexico City, Mexico
| | - Giovanny Soca-Chafre
- Oncological Diseases Research Unit (UIEO), Hospital Infantil de México Federico Gómez, Mexico City, Mexico
| | - Maria Rosa Avila-Costa
- Neuromorphology Laboratory, Facultad de Estudios Superiores Iztacala, UNAM, Mexico City, Mexico
| | | | | | | | - Emma Rodriguez-Maldonado
- Traslational Medicine Laboratory, Research Unit UNAM-INC, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
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Wu CC, Chung CH, Tzeng NS, Wu MJ, Tsao CH, Wu TH, Chien WC, Chen HC. The association between hormone therapy and the risk of lung cancer in postmenopausal women: a 16-year nationwide population-based study. Menopause 2023; 30:521-528. [PMID: 36854166 DOI: 10.1097/gme.0000000000002165] [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: 03/02/2023]
Abstract
OBJECTIVE Although an association between hormone therapy (HT) and the risk of developing lung cancer has been reported, the results on the topic are inconsistent. Our study objective was to investigate whether postmenopausal women who undergo HT exhibit a risk of developing lung cancer. METHODS In this matched cohort study, we obtained the data of 38,104 postmenopausal women older than 45 years who were treated using HT between 2000 and 2015 from Taiwan's National Health Insurance Research Database, and 152,416 matched participants who were not treated using HT were enrolled as controls at a 1:4 ratio. RESULTS We used a Cox proportional hazards regression model to identify the risk of developing lung cancer during 16 years of follow-up, and the results indicate no significant difference in the proportion of postmenopausal women treated using HT ( P = 0.129) who developed lung cancer and that of those not treated using HT (0.866% [330 of 38,104] vs 0.950% [1,449 of 152,416]). After adjustment for age and other variables, the adjusted hazard ratio was 0.886 (95% CI, 0.666-1.305, P = 0.433), indicating no association between HT and lung cancer development in postmenopausal women. In a subgroup analysis, the risk of lung cancer was significantly lower in the women who were treated using HT when the HT cumulative dosage was ≥401 mg or when the therapy duration was ≥5 years compared with in those not treated using HT; the adjusted hazard ratios were 0.633 (95% CI, 0.475-0.930; P < 0.001) and 0.532 (95% CI, 0.330-0.934; P < 0.001), respectively, after adjustment. CONCLUSIONS Our results indicate that HT is not associated with the risk of lung cancer development in postmenopausal women; furthermore, a higher cumulative dosage and the long-term effects of HT reduce the risk of developing lung cancer.
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Affiliation(s)
- Chia-Chen Wu
- From the Division of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | | | | | - Min-Jung Wu
- School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan
| | | | | | | | - Hsin-Chien Chen
- Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Dragani TA, Muley T, Schneider MA, Kobinger S, Eichhorn M, Winter H, Hoffmann H, Kriegsmann M, Noci S, Incarbone M, Tosi D, Franzi S, Colombo F. Lung Adenocarcinoma Diagnosed at a Younger Age Is Associated with Advanced Stage, Female Sex, and Ever-Smoker Status, in Patients Treated with Lung Resection. Cancers (Basel) 2023; 15:cancers15082395. [PMID: 37190323 DOI: 10.3390/cancers15082395] [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: 01/31/2023] [Revised: 04/06/2023] [Accepted: 04/19/2023] [Indexed: 05/17/2023] Open
Abstract
To date, the factors which affect the age at diagnosis of lung adenocarcinoma are not fully understood. In our study, we examined the relationships of age at diagnosis with smoking, pathological stage, sex, and year of diagnosis in a discovery (n = 1694) and validation (n = 1384) series of lung adenocarcinoma patients who had undergone pulmonary resection at hospitals in the Milan area and at Thoraxklinik (Heidelberg), respectively. In the discovery series, younger age at diagnosis was associated with ever-smoker status (OR = 1.5, p = 0.0035) and advanced stage (taking stage I as reference: stage III OR = 1.4, p = 0.0067; stage IV OR = 1.7, p = 0.0080), whereas older age at diagnosis was associated with male sex (OR = 0.57, p < 0.001). Analysis in the validation series confirmed the ever versus never smokers' association (OR = 2.9, p < 0.001), the association with highest stages (stage III versus stage I OR = 1.4, p = 0.0066; stage IV versus stage I OR = 2.0, p = 0.0022), and the male versus female sex association (OR = 0.78, p = 0.032). These data suggest the role of smoking in affecting the natural history of the disease. Moreover, aggressive tumours seem to have shorter latency from initiation to clinical detection. Finally, younger age at diagnosis is associated with the female sex, suggesting that hormonal status of young women confers risk to develop lung adenocarcinoma. Overall, this study provided novel findings on the mechanisms underlying age at diagnosis of lung adenocarcinoma.
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Affiliation(s)
- Tommaso A Dragani
- Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
| | - Thomas Muley
- Translational Research Unit (STF), Thoraxklinik, Heidelberg University Hospital, 69126 Heidelberg, Germany
- Translational Lung Research Center (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany
| | - Marc A Schneider
- Translational Research Unit (STF), Thoraxklinik, Heidelberg University Hospital, 69126 Heidelberg, Germany
- Translational Lung Research Center (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany
| | - Sonja Kobinger
- Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, 69126 Heidelberg, Germany
| | - Martin Eichhorn
- Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, 69126 Heidelberg, Germany
| | - Hauke Winter
- Translational Lung Research Center (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany
- Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, 69126 Heidelberg, Germany
| | - Hans Hoffmann
- Department of Thoracic Surgery, Klinikum Rechts der Isar, Technische Universität München, 81675 Munich, Germany
| | - Mark Kriegsmann
- Translational Lung Research Center (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany
- Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Sara Noci
- Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
| | - Matteo Incarbone
- Department of Surgery, IRCCS Multimedica, 20099 Sesto San Giovanni, Italy
| | - Davide Tosi
- Thoracic Surgery and Lung Transplantation, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Sara Franzi
- Thoracic Surgery and Lung Transplantation, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Francesca Colombo
- Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
- Institute for Biomedical Technologies, CNR, 20054 Segrate, Italy
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Hammouz RY, Orzechowska M, Anusewicz D, Bednarek AK. X or Y Cancer: An Extensive Analysis of Sex Differences in Lung Adenocarcinoma. Curr Oncol 2023; 30:1395-1415. [PMID: 36826068 PMCID: PMC9955992 DOI: 10.3390/curroncol30020107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 01/09/2023] [Accepted: 01/11/2023] [Indexed: 01/19/2023] Open
Abstract
Background: Cellular metabolism is a tightly controlled process during which cell growth and survival are maintained. Lung cancer is a disease with clear sex differences, where female patients have better survival rates than males. Evidence of sex differences is demonstrated in cancer risk, prognosis and response to different therapies, yet a sex-specific approach to cancer studies is not widely considered. These different tumour characteristics attributed to sex that impact disease outcome, including constitutional genetic and somatic molecular differences, make it essential to assess viral and hormonal influences. Methods: In silico analysis of lung adenocarcinoma (LUAD) TCGA data, including K-means clustering algorithm, dimensional reduction with principal component analysis and differential expression analysis using EdgeR (p < 0.05), were used to explore some robust sex differences in LUAD that exist in core signalling pathways and metabolic processes between males and females. The correlation of differentially expressed genes (DEGs) expression with immune abundance in the LUAD cohort was analysed on TIMER2.0 and adjusted by tumour purity utilising Cox proportional hazard. Multiple factorial analysis heatmap visualisation was used to examine endogenous steroid hormonal effects on LUAD patients with different smoking status and age groups. Results: We found 161 DEGs showing key differences in regulation of immune system and cellular homeostasis, key elements of divergent cancer progression, between the two sexes. We also found male and female LUAD patients to favour different metabolic intermediates for energy production to support tumourigenesis. Additionally, high levels of Tregs accompanied by DEGs correlated with better LUAD prognosis, and circulating hormonal transcriptional targets affect proliferation and progression in males and females differently. Finally, we examined the role of oestrogen protection in men and pre-/postmenopausal women. Conclusions: Further studies should focus on sex-specific changes and investigate sex-specific gene regulatory networks of these DEGs. Several lifestyle factors, including tobacco smoking and diet, differ between males and females. These factors might affect metabolic pathways and can influence the activity of epigenetic regulators, resulting in significant global epigenetic changes.
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Zhang C, Cheng Y, Chen W, Li Q, Dai R, Wang Y, Yang T. Association of CYP19A1 rs28757157 polymorphism with lung cancer risk in the Chinese Han population. World J Surg Oncol 2022; 20:400. [PMID: 36527059 PMCID: PMC9756459 DOI: 10.1186/s12957-022-02868-9] [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: 08/25/2022] [Accepted: 12/04/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Lung cancer is the leading cause of cancer death globally. Recent studies have revealed that CYP19A1 gene plays a crucial role in cancer initiation and development. The aim of this study was to assess the association of CYP19A1 genetic polymorphisms with the risk of lung cancer in the Chinese Han population. METHODS This study randomly recruited 489 lung cancer patients and 467 healthy controls. The genotypes of four single nucleotide polymorphisms (SNPs) of the CYP19A1 gene were identified by the Agena MassARRY technique. Genetic model analysis was used to assess the association between genetic variations and lung cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the effect of four selected SNPs on lung cancer risk. RESULTS CYP19A1 rs28757157 might contribute to an increased risk of lung cancer (p = 0.025, OR = 1.30, 95% CI 1.03-1.64). In stratified analysis, rs28757157 was associated with an increased cancer risk in the population aged under 60 years, females, smokers, and drinkers. Besides, rs3751592 and rs59429575 were also identified as risk biomarkers in the population under 60 years and drinkers. Meanwhile, a relationship between an enhanced risk of squamous cell carcinoma and rs28757157 was found, while the rs3751592 CC genotype was identified as a risk factor for lung adenocarcinoma development. CONCLUSIONS This study has identified revealed that the three SNPs (rs28757157, rs3751592, and rs59429575) of CYP19A1 are associated with lung cancer in the Chinese Han population. These findings will provide theoretical support for further functional studies of CYP19A1 in lung cancer.
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Affiliation(s)
- Chan Zhang
- grid.414918.1Department of Blood Transfusion, The First People’s Hospital of Yunnan Province, Kunming, 650032 Yunnan China
| | - Yujing Cheng
- grid.414918.1Department of Blood Transfusion, The First People’s Hospital of Yunnan Province, Kunming, 650032 Yunnan China
| | - Wanlu Chen
- grid.414918.1Department of Blood Transfusion, The First People’s Hospital of Yunnan Province, Kunming, 650032 Yunnan China
| | - Qi Li
- grid.414918.1Department of Blood Transfusion, The First People’s Hospital of Yunnan Province, Kunming, 650032 Yunnan China
| | - Run Dai
- grid.414918.1Department of Blood Transfusion, The First People’s Hospital of Yunnan Province, Kunming, 650032 Yunnan China
| | - Yajie Wang
- grid.414918.1Department of Hematology, The First People’s Hospital of Yunnan Province, Xishan District, #157 Jinbi Road, Kunming, 650032 Yunnan China
| | - Tonghua Yang
- grid.414918.1Department of Hematology, The First People’s Hospital of Yunnan Province, Xishan District, #157 Jinbi Road, Kunming, 650032 Yunnan China
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22
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Lu C, Cai Y, Liu W, Peng B, Liang Q, Yan Y, Liang D, Xu Z. Aberrant expression of KDM1A inhibits ferroptosis of lung cancer cells through up-regulating c-Myc. Sci Rep 2022; 12:19168. [PMID: 36357457 PMCID: PMC9649633 DOI: 10.1038/s41598-022-23699-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 11/03/2022] [Indexed: 11/11/2022] Open
Abstract
Ferroptosis is a cell death process caused by metabolic dysfunction with the feature of aberrant iron accumulation. Emerging studies have identified that ferroptosis is an important biological function involving in the tumorigenesis, and targeting ferroptosis could provide promising therapeutic targets for lung cancer. However, such therapeutic strategies show limited therapeutic effect owing to drug resistance and other unknown underlying mechanisms. In this study, lysine-specific demethylase 1 (LSD1/KDM1A) was found to be significantly upregulated in lung cancer cells and tissues. The patients with KDM1A downregulation displayed the good prognosis. Using gene set enrichment analysis (GSEA), we demonstrated that KDM1A-associated genes might participate in the regulation of cell ferroptosis and Myc signaling in lung cancer. Knockdown of KDM1A inhibited the level of c-Myc and increased the concentration of malondialdehyde (MDA) and irons in human lung cancer cells H1299 and A549. Downregulation of c-Myc could facilitate KDM1A knockdown-mediated ferroptosis. Our study has elucidated the effect of KDM1A/c-Myc regulatory axis in the ferroptosis resistance of lung cancer cells.
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Affiliation(s)
- Can Lu
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China
| | - Yuan Cai
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
| | - Wei Liu
- Department of Orthopedic Surgery, The Second Hospital University of South China, Hengyang, China
| | - Bi Peng
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
| | - Qiuju Liang
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China
| | - Yuanliang Yan
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
| | - Desheng Liang
- Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
| | - Zhijie Xu
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
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23
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Musial C, Knap N, Zaucha R, Bastian P, Barone G, Lo Bosco G, Lo-Celso F, Konieczna L, Belka M, Bączek T, Gammazza AM, Kuban-Jankowska A, Cappello F, Nussberger S, Gorska-Ponikowska M. Induction of 2-hydroxycatecholestrogens O-methylation: A missing puzzle piece in diagnostics and treatment of lung cancer. Redox Biol 2022; 55:102395. [PMID: 35841627 PMCID: PMC9289866 DOI: 10.1016/j.redox.2022.102395] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/15/2022] [Accepted: 07/02/2022] [Indexed: 02/07/2023] Open
Abstract
Lung cancer is one of the most common cancers worldwide, causing nearly one million deaths each year. Herein, we present the effect of 2-methoxyestradiol (2-ME), the endogenous metabolite of 17β-estradiol (E2), on non-small cell lung cancer (NSCLC) cells. We observed that 2-ME reduced the viability of lung adenocarcinoma in two-dimensional (2D) and three-dimensional (3D) spheroidal A549 cell culture models. Molecular modeling was carried out aiming to visualize amino acid residues within binding pockets of the acyl-protein thioesterases, namely 1 (APT1) and 2 (APT2), and thus to identify which ones were more likely involved in the interaction with 2-ME. Our findings suggest that 2-ME acts as an APT1 inhibitor enhancing protein palmitoylation and oxidative stress phenomena in the lung cancer cell. In order to support our data, metabolomics of blood serum from NSCLC patients was also performed. Moreover, computational analysis suggests that 2-ME as compared to other estrogen metabolism intermediates is relatively safe in terms of its possible non-receptor bioactivity within healthy human cells due to a very low electrophilic potential and hence no substantial risk of spontaneous covalent modification of biologically protective nucleophiles. We propose that 2-ME can be used as a selective tumor biomarker in the course of certain types of lung cancers and possibly as a therapeutic adjuvant or neoadjuvant.
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Affiliation(s)
- Claudia Musial
- Department of Medical Chemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, Poland
| | - Narcyz Knap
- Department of Medical Chemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, Poland
| | - Renata Zaucha
- Department of Clinical Oncology and Radiotherapy, Medical University of Gdansk, 80-214, Gdansk, Poland
| | - Paulina Bastian
- Department of Medical Chemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, Poland
| | - Giampaolo Barone
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90128, Palermo, Italy
| | - Giosuè Lo Bosco
- Department of Mathematics and Computer Science, University of Palermo, 90133, Palermo, Italy; Euro-Mediterranean Institute of Science and Technology, 90139, Palermo, Italy
| | - Fabrizio Lo-Celso
- Department of Physics and Chemistry 'Emilio Segrè', University of Palermo, 90128, Palermo, Italy
| | - Lucyna Konieczna
- Department of Pharmaceutical Chemistry, Medical University of Gdansk, 80-416, Gdansk, Poland
| | - Mariusz Belka
- Department of Pharmaceutical Chemistry, Medical University of Gdansk, 80-416, Gdansk, Poland
| | - Tomasz Bączek
- Department of Pharmaceutical Chemistry, Medical University of Gdansk, 80-416, Gdansk, Poland
| | - Antonella Marino Gammazza
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127, Palermo, Italy
| | - Alicja Kuban-Jankowska
- Department of Medical Chemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, Poland
| | - Francesco Cappello
- Euro-Mediterranean Institute of Science and Technology, 90139, Palermo, Italy; Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127, Palermo, Italy
| | - Stephan Nussberger
- Department of Biophysics, Institute of Biomaterials and Biomolecular Systems, University of Stuttgart, 70569, Stuttgart, Germany
| | - Magdalena Gorska-Ponikowska
- Department of Medical Chemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, Poland; Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90128, Palermo, Italy; Euro-Mediterranean Institute of Science and Technology, 90139, Palermo, Italy; Department of Biophysics, Institute of Biomaterials and Biomolecular Systems, University of Stuttgart, 70569, Stuttgart, Germany.
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24
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Xu M, Li M, Pei J, Wu C, Jiang L, Jiang M, Zhu C. Gender disparities in incidence and projections of lung cancer in China and the United States from 1978 to 2032: an age-period-cohort analysis. Cancer Causes Control 2022; 33:1247-1259. [PMID: 35916964 DOI: 10.1007/s10552-022-01597-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 06/11/2022] [Indexed: 11/24/2022]
Abstract
PURPOSE Lung cancer incidences tend to be higher among males than females in both China and the United States, yet secular incidence patterns are different due to distinct population and environmental exposures. We examined long-term and future trends of lung cancer incidence, as well as the associations of age, period, and cohort effects with gender disparities. METHODS Using data from the Cancer Incidence in Five Continents from 1978 to 2012, we calculated age-standardized, age-specific incidence, and male-to-female incidence rate ratios (IRR), and conducted an age-period-cohort analysis. The average annual percentage change (AAPC) of the trends was obtained by Joinpoint Regression. Bayesian age-period-cohort analysis was also conducted to project incidences to 2032. RESULTS In China, age-standardized incidence revealed a decreasing trend among males, but showed increasing trends among the younger age groups (30-54 years) in females. Age-standardized incidence rates of males decreased but remained stable among females from 1972 to 2012 in the United States. Male-to-female incidence rate ratios narrowed in both countries and reversed among younger birth cohorts in the United States. Gender disparities are expected to continue to diminish in both countries, and incidence among females appears to exceed that of males in the United States by around 2023-2027. CONCLUSION Gender disparities in lung cancer incidence persist and will continue into the future in both countries, but our findings suggested that smoking may play different roles in gender disparities in lung cancer incidence between the two countries. Further population-based epidemiological studies among females in China are imperative.
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Affiliation(s)
- Minghan Xu
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Mandi Li
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Jiao Pei
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.,Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Chenyao Wu
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Lin Jiang
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Min Jiang
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
| | - Cairong Zhu
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
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25
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Jeon DS, Kim JW, Kim SG, Kim HR, Song SY, Lee JC, Ji W, Choi CM, Kim HC. Sex differences in the characteristics and survival of patients with non-small-cell lung cancer: A retrospective analytical study based on real-world clinical data of the Korean population. Thorac Cancer 2022; 13:2584-2591. [PMID: 35906163 PMCID: PMC9475225 DOI: 10.1111/1759-7714.14594] [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: 06/13/2022] [Revised: 07/09/2022] [Accepted: 07/11/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose This study aimed to investigate the differences in characteristics, clinical stages, treatment modalities, and survival outcomes in patients with non‐small‐cell lung cancer (NSCLC) based on sex differences using Korean nationwide registry data. Methods We analyzed the data of 8650 patients diagnosed with NSCLC between 2014 and 2017, obtained from the Korean Association for Lung Cancer Registry (KALC‐R). The Cox proportional hazard model was used to define the differences in survival based on sex. Propensity score matching was used to adjust for differences between men and women. Results Of a total of 10 943 patients, 8650 (79.1%) were diagnosed with NSCLC, of whom 68.7% were men and 31.3% were women. For NSCLC, the median age was higher (69.0 vs. 67.0, p < 0.001) and the proportion of ever‐smokers (84.5% vs. 10.8%, p < 0.001) was higher in men. Adenocarcinoma (55.5% vs. 90.4%, p < 0.001) and stage I NSCLC (26.3% vs. 41.3%, p < 0.001) were more common in women. Survival was significantly lower in men with NSCLC (hazard ratio [HR] 1.493 [95% confidence interval, CI 1.238–1.800], p < 0.001) even after adjusting for meaningful clinical variables, and in the matched cohort (HR 1.339 [1.075–1.667], p = 0.009). Similarly, survival was significantly lower in men with stage IV adenocarcinoma after adjusting for other clinical variables (HR 1.493 [1.238–1.800], p < 0.001) and in the matched cohort (HR 1.339 [1.075–1.667]; p = 0.009). Conclusions Male patients with NSCLC had poorer prognosis, not only after variable adjustments for prognostic factors, but also in the matched cohort.
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Affiliation(s)
- Da Som Jeon
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jin Woo Kim
- Respiratory and Pulmonary Disease Laboratory, Biomedical Research Center, Asan Medical Center, Seoul, South Korea
| | - Seul Gi Kim
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Hyeong Ryul Kim
- Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Si Yeol Song
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jae Cheol Lee
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Wonjun Ji
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Chang-Min Choi
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.,Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ho Cheol Kim
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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26
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Saed L, Jeleń A, Mirowski M, Sałagacka-Kubiak A. Prognostic Significance of HMGA1 Expression in Lung Cancer Based on Bioinformatics Analysis. Int J Mol Sci 2022; 23:ijms23136933. [PMID: 35805937 PMCID: PMC9266824 DOI: 10.3390/ijms23136933] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 06/18/2022] [Accepted: 06/18/2022] [Indexed: 12/15/2022] Open
Abstract
High-mobility group protein 1 (HMGA1) participates in the processes of DNA transcription, replication, recombination, and repair. The HMGA1 gene is expressed abundantly during embryogenesis and is reactivated during carcinogenesis. HMGA1 gene expression has been associated with a high degree of malignancy, metastatic tendency, and poor survival in breast, colon, ovary, and pancreatic cancers. However, its prognostic significance in lung cancer remains unclear. Using publicly available data, HMGA1 was shown to be overexpressed in both small and non-small lung tumors, with higher expression compared to both the adjacent non-malignant lung tissues and non-tumor lung tissues of healthy individuals. Elevated HMGA1 expression could result from lowered HMGA1 methylation and was connected with some clinicopathological features like sex, age, and stage of the disease. The high HMGA1 expression level was connected with shorter overall and first progression survival time among lung adenocarcinoma patients, but not lung squamous cell carcinoma patients. HMGA1 could interact with proteins involved in cellular senescence and cell cycle control (TP53, RB1, RPS6KB1, and CDK1), transcription regulation (EP400 and HMGA2), chromatin assembly and remodeling (LMNB1), and cholesterol and isoprene biosynthesis (HMGCR and INSIG1). Taken together, HMGA1 overexpression could be an essential element of lung carcinogenesis and a prognostic feature in lung cancer.
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27
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Chen S, Zhang J, Li Q, Xiao L, Feng X, Niu Q, Zhao L, Ma W, Ye H. A Novel Secreted Protein-Related Gene Signature Predicts Overall Survival and Is Associated With Tumor Immunity in Patients With Lung Adenocarcinoma. Front Oncol 2022; 12:870328. [PMID: 35719915 PMCID: PMC9204015 DOI: 10.3389/fonc.2022.870328] [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: 02/08/2022] [Accepted: 05/09/2022] [Indexed: 12/01/2022] Open
Abstract
Secreted proteins are important proteins in the human proteome, accounting for approximately one-tenth of the proteome. However, the prognostic value of secreted protein-related genes has not been comprehensively explored in lung adenocarcinoma (LUAD). In this study, we screened 379 differentially expressed secretory protein genes (DESPRGs) by analyzing the expression profile in patients with LUAD from The Cancer Genome Atlas database. Following univariate Cox regression and least absolute shrinkage and selection operator method regression analysis, 9 prognostic SPRGs were selected to develop secreted protein-related risk score (SPRrisk), including CLEC3B, C1QTNF6, TCN1, F2, FETUB, IGFBP1, ANGPTL4, IFNE, and CCL20. The prediction accuracy of the prognostic models was determined by Kaplan–Meier survival curve analysis and receiver operating characteristic curve analysis. Moreover, a nomogram with improved accuracy for predicting overall survival was established based on independent prognostic factors (SPRrisk and clinical stage). The DESPRGs were validated by quantitative real-time PCR and enzyme-linked immunosorbent assay by using our clinical samples and datasets. Our results demonstrated that SPRrisk can accurately predict the prognosis of patients with LUAD. Patients with a higher risk had lower immune, stromal, and ESTIMATE scores and higher tumor purity. A higher SPRrisk was also negatively associated with the abundance of CD8+ T cells and M1 macrophages. In addition, several genes of the human leukocyte antigen family and immune checkpoints were expressed in low levels in the high-SPRrisk group. Our results provided some insights into assessing individual prognosis and choosing personalized treatment modalities.
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Affiliation(s)
- Shuaijun Chen
- Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun Zhang
- Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qian Li
- Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lingyan Xiao
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiao Feng
- Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qian Niu
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liqin Zhao
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wanli Ma
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Respiratory Diseases, National Health Commission of China, Wuhan, China
| | - Hong Ye
- Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Respiratory Diseases, National Health Commission of China, Wuhan, China
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28
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Bae JM. Use of oral contraceptives and risk of pancreatic cancer in women: A recalculated meta-analysis of prospective cohort studies. World J Gastroenterol 2021; 27:8374-8377. [PMID: 35068876 PMCID: PMC8717024 DOI: 10.3748/wjg.v27.i48.8374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 10/25/2021] [Accepted: 12/22/2021] [Indexed: 02/06/2023] Open
Abstract
In a recent systematic review and meta-analysis of observational studies, the author found potential errors in the selection and extraction processes. The recalculated summary relative risks and the results of a dose-response meta-analysis showed that oral contraceptive use may not be associated with the risk of pancreatic cancer in women.
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Affiliation(s)
- Jong-Myon Bae
- Preventive Medicine, Jeju National University College of Medicine, Jeju-si 63243, Jeju Province, South Korea
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29
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Targeting Estrogens and Various Estrogen-Related Receptors against Non-Small Cell Lung Cancers: A Perspective. Cancers (Basel) 2021; 14:cancers14010080. [PMID: 35008242 PMCID: PMC8750572 DOI: 10.3390/cancers14010080] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 12/08/2021] [Accepted: 12/16/2021] [Indexed: 12/20/2022] Open
Abstract
Non-small cell lung cancers (NSCLCs) account for ~85% of lung cancer cases worldwide. Mammalian lungs are exposed to both endogenous and exogenous estrogens. The expression of estrogen receptors (ERs) in lung cancer cells has evoked the necessity to evaluate the role of estrogens in the disease progression. Estrogens, specifically 17β-estradiol, promote maturation of several tissue types including lungs. Recent epidemiologic data indicate that women have a higher risk of lung adenocarcinoma, a type of NSCLC, when compared to men, independent of smoking status. Besides ERs, pulmonary tissues both in healthy physiology and in NSCLCs also express G-protein-coupled ERs (GPERs), epidermal growth factor receptor (EGFRs), estrogen-related receptors (ERRs) and orphan nuclear receptors. Premenopausal females between the ages of 15 and 50 years synthesize a large contingent of estrogens and are at a greater risk of developing NSCLCs. Estrogen-ER/GPER/EGFR/ERR-mediated activation of various cell signaling molecules regulates NSCLC cell proliferation, survival and apoptosis. This article sheds light on the most recent achievements in the elucidation of sequential biochemical events in estrogen-activated cell signaling pathways involved in NSCLC severity with insight into the mechanism of regulation by ERs/GPERs/EGFRs/ERRs. It further discusses the success of anti-estrogen therapies against NSCLCs.
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