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Hadizadeh M, Askari N, Jafarinejad-Farsangi S. A single-cell approach to analyzing vascular endothelial cell contributions in VEGF-driven angiogenesis and LINC02313 in gastric cancer. Comput Biol Chem 2025; 115:108361. [PMID: 39914073 DOI: 10.1016/j.compbiolchem.2025.108361] [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: 12/08/2024] [Revised: 01/11/2025] [Accepted: 01/21/2025] [Indexed: 02/26/2025]
Abstract
Gastric cancer (GC) heterogeneity and lack of suitable molecular markers remain major challenges for this disease. The critical role of long non-coding RNAs (lncRNAs) in cancer biological processes has been increasingly recognized. A novel lncRNA, LINC02313, was identified in GC in this study, and its function was examined bioinformatically. The differential expression of LINC02313 was examined, and its target genes were predicted using RNA-Seq data from TCGA. LINC02313 showed correlation with 272 significant DEGs in GC. The analysis of single-cell transcriptomes revealed 11 unique clusters of cell types, but vascular endothelial cells have the most targets (30 genes). Receiver Operating Characteristic (ROC) analysis illustrated the diagnostic capabilities of LINC02313 and its targets across most cellular clusters, achieving the highest levels of accuracy. Functionally related signaling pathways were classified through cell-cell communication analysis; in the tumorous state, emphasizing the more prominent role of vascular endothelial cells in the Vascular Endothelial Growth Factor (VEGF) signaling pathway compared to the normal state. Trajectory analysis showed vascular endothelial cells are at the start of pseudotime in a normal state, but in a tumorous state, they shift to the middle of pseudotime. The results of this study highlight the critical role of endothelial cells in the advancement of GC and propose novel therapeutic approaches that focus on modulating angiogenic signaling pathways and lncRNA function to enhance treatment efficacy.
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Affiliation(s)
- Morteza Hadizadeh
- Department of Biotechnology, Institute of Sciences and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran
| | - Nahid Askari
- Department of Biotechnology, Institute of Sciences and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.
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Wang S, Li J, Zhang Z, Cao S, Zhang Z, Bian Y, Xu Y, Ma C. Advances in nanomedicine and delivery systems for gastric cancer research. Front Bioeng Biotechnol 2025; 13:1565999. [PMID: 40190709 PMCID: PMC11968739 DOI: 10.3389/fbioe.2025.1565999] [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: 01/24/2025] [Accepted: 03/05/2025] [Indexed: 04/09/2025] Open
Abstract
The early diagnosis rate of gastric cancer is low, and most patients are already at an advanced stage by the time they are diagnosed, posing significant challenges for treatment and exhibiting high recurrence rates, which notably diminish patients' survival time and quality of life. Therefore, there is an urgent need to identify methods that can enhance treatment efficacy. Nanomedicine, distinguished by its small size, high targeting specificity, and strong biological compatibility, is particularly well-suited to address the toxic side effects associated with current diagnostic and therapeutic approaches for gastric cancer. Consequently, the application of nanomedicine and delivery systems in the diagnosis and treatment of gastric cancer has garnered increasing interest from researchers. This review provides an overview of recent advancements in the use of nanomaterials as drugs or drug delivery systems in gastric cancer research, encompassing their applications in diagnosis, chemotherapy, radiotherapy, surgery, and phototherapy, and explores the promising prospects of nanomedicine in the treatment of gastric cancer.
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Affiliation(s)
- Sizhe Wang
- Henan University of Chinese Medicine(The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Jilei Li
- Henan Province Hospital of TCM, Zhengzhou(The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Zhenyu Zhang
- Henan University of Chinese Medicine(The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Shasha Cao
- Henan University of Chinese Medicine(The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Zihan Zhang
- Henan University of Chinese Medicine(The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Yifan Bian
- Henan University of Chinese Medicine(The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Yanchao Xu
- Henan Province Hospital of TCM, Zhengzhou(The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Chunzheng Ma
- Henan Province Hospital of TCM, Zhengzhou(The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou, Henan, China
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Chen P, Ni S, Ou-Yang L. Causal inference of inflammatory proteins in infertility: a Mendelian randomization study. Front Endocrinol (Lausanne) 2025; 16:1448530. [PMID: 40070583 PMCID: PMC11893426 DOI: 10.3389/fendo.2025.1448530] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 02/05/2025] [Indexed: 03/14/2025] Open
Abstract
Background Infertility affects 8-12% of couples globally, manifesting as a complex reproductive disorder with varied causes, negatively impacting emotional, physical, and social well-being. Inflammation is implicated in many diseases, including male and female infertility. Methods This study employed Mendelian randomization (MR) with two-sample, bidirectional, and mediation approaches to explore the relationship between circulating inflammatory proteins and infertility. Causal analysis was conducted using inverse variance-weighted (IVW) and MR-Egger regression, supplemented by enrichment analysis, protein-protein interaction (PPI) network exploration, and drug signature analysis. Results Our findings identified a significant positive correlation between C-X-C motif chemokine 6 (CXCL6) and male infertility, positioning CXCL6 as a potential therapeutic target or biomarker. No causal links were detected between circulating inflammatory proteins and female infertility post-FDR adjustment. Minor mediation effects were observed for metabolites such as androstenediol monosulfate, arachidonoylcholine, and serum phosphate to glycerol ratio. Cytokine-related pathways emerged as significant in both male and female infertility. Gene-drug interaction analysis highlighted the need for further investigation of pioglitazone in treating female infertility. Conclusion This study establishes a potentially causal relationship between CXCL6 and male infertility, suggesting its potential as a drug target or molecular biomarker. The integrative approach combining causal inference with molecular pathway and drug interaction analysis opens new avenues for understanding and treating infertility.
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Affiliation(s)
| | - Sha Ni
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
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Jiang YK, Li W, Qiu YY, Yue M. Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer. World J Gastrointest Oncol 2024; 16:2318-2334. [PMID: 38994153 PMCID: PMC11236256 DOI: 10.4251/wjgo.v16.i6.2318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 04/04/2024] [Accepted: 04/18/2024] [Indexed: 06/13/2024] Open
Abstract
Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance. Human epidermal growth factor receptor 2 (HER2) is one of the most important targets in targeted therapy for gastric cancer. Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer. The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified. However, monoclonal antibodies, due to their large molecular weight, inability to penetrate the blood-brain barrier, and drug resistance, lead to decreased therapeutic efficacy, so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer. Small-molecule tyrosine kinase inhibitors, such as lapatinib and pyrrotinib, have the advantages of small molecular weight, penetrating the blood-brain barrier and high oral bioavailability, and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future. Antibo-drug conjugate, such as T-DM1 and T-DXd, can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing, and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab. Therefore, after more detailed stratification of gastric cancer patients, various gastric cancer drugs targeting HER2 are expected to play a more significant role.
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Affiliation(s)
- Ya-Kun Jiang
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
| | - Wei Li
- Health Management Center, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
| | - Ying-Yang Qiu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Meng Yue
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
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Yang L, Du YE, Liao F, Huang T, Liu Y, Liu J, Wang C, Zhan Z, Cao Y, Wang Z, Chen W. A novel combined therapeutic strategy of Nano-EN-IR@Lip mediated photothermal therapy and stem cell inhibition for gastric cancer. Biomed Pharmacother 2024; 174:116486. [PMID: 38520865 DOI: 10.1016/j.biopha.2024.116486] [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: 12/19/2023] [Revised: 03/07/2024] [Accepted: 03/19/2024] [Indexed: 03/25/2024] Open
Abstract
Recurrence and metastasis of gastric cancer is a major therapeutic challenge for treatment. The presence of cancer stem cells (CSCs) is a major obstacle to the success of current cancer therapy, often leading to treatment resistance and tumor recurrence and metastasis. Therefore, it is important to develop effective strategies to eradicate CSCs. In this study, we developed a combined therapeutic strategy of photothermal therapy (PTT) and gastric cancer stem cells (GCSCs) inhibition by successfully synthesizing nanoliposomes loaded with IR780 (photosensitizer) and EN4 (c-Myc inhibitor). The nanocomposites are biocompatible and exhibit superior photoacoustic (PA) imaging properties. Under laser irradiation, IR780-mediated PTT effectively and rapidly killed tumor cells, while EN4 synergistically inhibited the self-renewal and stemness of GCSCs by suppressing the expression and activity of the pluripotent transcription factor c-Myc, preventing the tumor progression of gastric cancer. This Nano-EN-IR@Lip is expected to be a novel clinical nanomedicine for the integration of gastric cancer diagnosis, treatment and prevention.
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Affiliation(s)
- Liping Yang
- Department of Laboratory Medicine, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
| | - Yan-E Du
- Department of Laboratory Medicine, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
| | - Fangli Liao
- Department of Laboratory Medicine, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
| | - Tong Huang
- State Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yadong Liu
- State Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Junzhao Liu
- State Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Can Wang
- State Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhu Zhan
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yang Cao
- State Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhigang Wang
- State Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Weixian Chen
- Department of Laboratory Medicine, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
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