Discover. Oncology最新文献

{"title":"Association between allopurinol and hepatocellular carcinoma: analysis of genetic risk and patient survival.","authors":"Yu-Fu Li, Hui-Wei Wang, Huan-Yan Peng, Zhen-Ying Zhang, Zhi-Jia Yao, Yuan Meng, Dong-Ye Yang","doi":"10.1007/s12672-025-02176-0","DOIUrl":"10.1007/s12672-025-02176-0","url":null,"abstract":"<p><strong>Background: </strong>Despite the widespread clinical use of allopurinol for managing hepatocellular carcinoma (HCC) and gout, its potential hepatotoxicity and its effect on the risk of HCC remain unclear. This study aimed to comprehensively assess the potential correlations between allopurinol exposure and HCC risk.</p><p><strong>Methods: </strong>We utilized genome-wide association study data from the IEU OpenGWAS project as instrumental variables (IVs) for Mendelian randomization (MR) analysis to investigate the causal relationship between allopurinol and HCC. Subsequently, we investigated the potential mediating factors (gout, liver fat, and percentage of liver fat, etc.) between allopurinol use and HCC. Furthermore, we analyzed assessed survival outcomes using the Kaplan-Meier method to compare patient subgroups by differential Xanthine dehydrogenase (XDH) expression.</p><p><strong>Results: </strong>MR analysis established a causal link between allopurinol use and increased HCC risk (OR: 1.013, 95% CI 1.004-1.023, p = 0.006). Causal relationships were also observed between gout (OR: 1.011, p = 0.008) and HCC. Mediation analysis indicated that gout mediated 61.6% of the effect of allopurinol on HCC. Survival analysis showed that higher expression of XDH was associated with improved survival of HCC patients (HR = 0.62, 95% CI 0.441-0.884, p = 0.008), indicating a 38% decrease in mortality risk compared to the lower expression group.</p><p><strong>Conclusions: </strong>This study demonstrated a causal relationship between allopurinol use and an increased risk of HCC based on genetic evidence. Allopurinol should be used with caution in patients with or at risk for HCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"454"},"PeriodicalIF":2.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A two-decade bibliometric analysis of drug resistance in oral cancer research: patterns, trends, and future directions.","authors":"Xuejin Xu, Zhen Wang","doi":"10.1007/s12672-025-02225-8","DOIUrl":"10.1007/s12672-025-02225-8","url":null,"abstract":"<p><strong>Background: </strong>Drug resistance in oral cancer presents a significant challenge in clinical treatment. Understanding the research landscape through bibliometric analysis can provide valuable insights into the development and trends in this field.</p><p><strong>Objective: </strong>To comprehensively analyze the global research trends, collaboration patterns, and emerging topics in oral cancer drug resistance research from 2000 to 2024 using bibliometric methods.</p><p><strong>Methods: </strong>Publications related to oral cancer drug resistance were retrieved from the Web of Science core collection database. CiteSpace and VOSviewer were employed to analyze publication trends, research collaboration networks, and keyword co-occurrence patterns. The analysis included annual publication outputs, country contributions, institutional productivity, author collaborations, journal distributions, and research hotspots.</p><p><strong>Results: </strong>A total of 971 publications were identified, showing a significant increase in research output over the study period, particularly after 2014. China led in publication output (485 articles), followed by Japan (130 articles) and the United States (118 articles). China Medical University was the most productive institution (50 publications). The International Journal of Molecular Sciences, Cancers, and Oral Oncology were the primary publishing venues. Keyword analysis revealed an evolution from basic drug resistance mechanisms to emerging research areas including cancer stem cells, tumor microenvironment, and extracellular vesicles.</p><p><strong>Conclusions: </strong>This bibliometric analysis demonstrates the rapid growth and evolving nature of oral cancer drug resistance research. The findings highlight the shift towards more sophisticated research areas and strong international collaboration patterns. These insights can guide future research directions and collaboration opportunities in this field.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"441"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding colorectal cancer targeted therapy: a bibliometric journey of the last decade (2015-2024).","authors":"Linpo Zhou, Xuanwei Huang, Jing Shi, Yebin Yang, Fanhe Dong, Haoran Wei, Chenghao Ji, Yuqiang Shan","doi":"10.1007/s12672-025-02251-6","DOIUrl":"10.1007/s12672-025-02251-6","url":null,"abstract":"<p><p>Colorectal cancer remains one of the most commonly diagnosed cancers globally, with a significant impact on public health. Targeted therapies have revolutionized the treatment landscape for colorectal cancer by offering increased specificity and reduced systemic toxicity compared to conventional chemotherapy. This study provides a comprehensive bibliometric analysis of global research on targeted therapy for colorectal cancer, focusing on publications from 2015 to 2024. A total of 3213 publications were retrieved from the Web of Science Core Collection and analyzed using bibliometric tools to construct knowledge maps and visualize research trends. The regression analysis shows a strong upward trend in publications from 2015 to 2024 (P < 0.001, R² = 0.889). China leads in publication output, with the University of Texas MD Anderson Cancer Center contributing the highest number of studies. Tabernero and Kopetz are the core authors in the field. Research in this domain has primarily concentrated on the development and clinical assessment of drugs targeting the EGFR, RAS, VEGF, and BRAF signaling pathways, as well as investigating the pathogenesis, drug resistance, and metastatic mechanisms of colorectal cancer. Current advancements emphasize Artificial Intelligence-driven multi-omics integration, the creation of novel therapeutics targeting established molecular pathways, and the execution of global clinical trials to validate personalized treatment strategies.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"442"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of cellular senescence-associated genes for predicting the diagnosis, prognosis and immunotherapy response in lung adenocarcinoma via a 113-combination machine learning framework.","authors":"Ting Ge, Guixin He, Qian Cui, Shuangcui Wang, Zekun Wang, Yingying Xie, Yuanyuan Tian, Juyue Zhou, Jianchun Yu, Jinmin Hu, Wentao Li","doi":"10.1007/s12672-025-02262-3","DOIUrl":"10.1007/s12672-025-02262-3","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is a prevalent malignant tumor of the respiratory system, with high incidence and mortality rates. Cellular senescence (CS) widely affects the tumor microenvironment (TME) and tumor growth, and is related to the invasion and immune escape of tumor cells. This study aims to develop a robust CS-related signature of LUAD.</p><p><strong>Methods: </strong>Using the GSE140797, GSE42458, GSE75037, and GSE85841 datasets, in combination with cellular senescence databases, 75 LUAD CS-related differentially expressed genes (LUAD-CSDEGs) were identified through the weighted gene co-expression network analysis (WGCNA) method. Subsequently, we developed a novel machine learning framework that incorporated 12 machine learning algorithms and their 113 combinations to construct a LUAD CS-related signature (LUAD-CSRS), which were assessed in both training and validation cohorts. A LUAD-CSRS-integrated nomogram was constructed to provide a quantitative tool for predicting prognosis in clinical practice. Finally, the difference of immune infiltration and response to immunotherapy in patients with high and low risk of LUAD were evaluated.</p><p><strong>Results: </strong>Based on a 113-combination machine learning framework, we finally identified a LUAD-CSRS containing eight genes: RECQL4, TIMP1, ANLN, SFN, MDK, KIF2C, AGR2, ITGB4. We also confirmed that it was significantly associated with survival, immune cell infiltration, prognosis, and response to immunotherapy in LUAD patients. Additionally, we found it is related to the activation of immune responses and may be involved in regulating the balance between immune cells in the TME.</p><p><strong>Conclusion: </strong>In summary, our study constructed a novel LUAD-CSRS, which is not only expected to be a powerful tool for assisting diagnosis and prognosis evaluation of LUAD, but also may provide guidance for personalized immunotherapy programs.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"440"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the key roles in esophageal cancer drug resistance from a genetic perspective: the interplay between cytokines and immune cell phenotypes.","authors":"Huishen Yan, Zhiwu Lin, Jieying Zhang, Peiquan Zhu, Yuquan Chen, Jingyuan Liao","doi":"10.1007/s12672-025-02074-5","DOIUrl":"10.1007/s12672-025-02074-5","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer (EC) is a common malignant tumor, often diagnosed in its late stages due to the subtlety of early symptoms. Traditional chemotherapy inflicts significant harm on the organism; however, the emergence of targeted and immune therapies has conferred considerable survival advantages for patients with EC. However, the prolonged exposure of immune cells to the tumor microenvironment (TME) results in functional deterioration, thereby causing drug resistance and notably diminishing the therapeutic outcomes. Therefore, it is necessary to gain an in-depth understanding of the immune microenvironment of EC to find ways to overcome the development of resistance.</p><p><strong>Objective: </strong>This study aimed to explore the causal relationships between cytokines, immune cell phenotypes, and the development of EC, with particular emphasis on their role in tumor progression and drug resistance. Using Mendelian randomization, we sought to identify key immune-related factors implicated in EC pathogenesis and evaluate their potential as therapeutic targets for overcoming resistance to treatment.</p><p><strong>Results: </strong>Through univariable MR, we found that two cytokines and twenty-two immune cell phenotypes are significantly associated with the incidence of EC. Further bidirectional MR analysis indicated interactions between two cytokines and five immune cells. Lastly, two-step MR analysis showed that there are mediating pathways in both directions between cytokines and immune cell phenotypes.</p><p><strong>Conclusion: </strong>This research deepens the understanding of the mechanisms underlying the interactions between key cytokines and immune cells associated with the onset of EC. The research provides new insights into the issue of drug resistance within the esophageal cancer TME and offers novel perspectives for the development of targeted and immune-based therapies for EC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"443"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The current landscape of artificial intelligence in computational histopathology for cancer diagnosis.","authors":"Aaditya Tiwari, Aruni Ghose, Maryam Hasanova, Sara Socorro Faria, Srishti Mohapatra, Sola Adeleke, Stergios Boussios","doi":"10.1007/s12672-025-02212-z","DOIUrl":"10.1007/s12672-025-02212-z","url":null,"abstract":"<p><p>Artificial intelligence (AI) marks a frontier in histopathologic analysis shift towards the clinic, becoming a mainstream choice to interpret histological images. Surveying studies assessing AI applications in histopathology from 2013 to 2024, we review key methods (including supervised, unsupervised, weakly supervised and transfer learning) in deep learning-based pattern recognition in computational histopathology for diagnostic and prognostic purposes. Deep learning methods also showed utility in identifying a wide range of genetic mutations and standard pathology biomarkers from routine histology. This survey of 41 primary studies also encompasses key regions of AI applicability in histopathology in a multi-cancer review while marking prospects to introduce AI into the clinical setting with key examples including Swarm Learning and Data Fusion.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"438"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-221 is a prognostic marker and promotes the proliferation and migration of esophageal squamous cell carcinoma by inhibiting autophagy.","authors":"Kun Mei, Zilu Chen, Foxing Tan, YuHeng Zhou, Haolin Du, Renjun Gu, Yan Huang","doi":"10.1007/s12672-025-02223-w","DOIUrl":"10.1007/s12672-025-02223-w","url":null,"abstract":"<p><strong>Purpose: </strong>Esophageal squamous cell carcinoma (ESCC) is a globally prevalent malignancy with high mortality rates. Elucidating the underlying pathophysiological mechanisms of ESCC tumorigenesis is critical for advancing its diagnosis and treatment. MicroRNAs (miRNAs) are pivotal regulators of tumor progression, exerting their effects by binding to target mRNAs and modulating mRNA translation as well as downstream signaling pathways. While the functional roles of numerous miRNAs in ESCC remain incompletely understood, existing studies have implicated autophagy deficiency in aging, cancer, and neurodegenerative diseases. Despite these insights, the relationship between miRNAs and autophagy in ESCC has been insufficiently explored. This study investigates the role of miRNA-221 (miR-221) in ESCC and its interaction with autophagy.</p><p><strong>Methods: </strong>Bioinformatics analysis was employed to determine the biological relevance of miR-221 in ESCC. RT-qPCR was utilized to quantify miR-221 expression in ESCC tissues and cell lines. The effects of miR-221 overexpression or knockdown on cell proliferation and migration were assessed using Cell Counting Kit-8 (CCK8), EdU, and Transwell assays. Western blot analysis was conducted to evaluate autophagy-related changes in ESCC cell lines.</p><p><strong>Results: </strong>The findings demonstrate that elevated miR-221 expression in tissues from patients with ESCC is a potential independent prognostic marker. Overexpression of miR-221 enhances tumorigenic and metastatic capabilities in ESCC cell lines by suppressing autophagy. Notably, rapamycin-induced autophagy activation partially mitigated the tumor-promoting effects of miR-221 on proliferation and migration.</p><p><strong>Conclusion: </strong>The interaction between miR-221 and autophagy presents a promising therapeutic target for ESCC management.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"445"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating tumor DNA in colorectal cancer: biology, methods and applications.","authors":"Han Chen, Yang An, Chentong Wang, Jiaolin Zhou","doi":"10.1007/s12672-025-02220-z","DOIUrl":"10.1007/s12672-025-02220-z","url":null,"abstract":"<p><p>In the practice of colorectal cancer (CRC), traditional tumor tissue analysis is limited by intratumoral and intertumoral heterogeneity and its invasive nature. Circulating tumor DNA (ctDNA) analysis, a promising liquid biopsy approach, has been increasingly explored in clinical studies. Biologically, ctDNA is characterized by tumor-specific diversity and rapid clearance from circulation, enabling real-time, dynamic, and repeatable assessments. Technologically, PCR- and NGS-based downstream analysis methods have been developed and validated. However, variables in pre-analytical and analytical procedures underscores the need for standardized protocols. Compared with clinicopathology-based risk stratification, ctDNA-based molecular residual disease detection has demonstrated significant potential in guiding treatment decisions. Qualitative and quantitative changes in ctDNA have also shown predictive and prognostic value during neoadjuvant or adjuvant treatment, as well as in later-line treatment for metastatic CRC. Specific molecular aberrations in ctDNA can not only assist in identifying candidates for targeted therapies but also reveal resistance mechanisms. Additionally, emerging research is exploring the potential of ctDNA in early cancer detection. Overall, as a novel biomarker, ctDNA holds substantial promise in advancing clinical practice. This review focuses on the biological characteristics, pre-analytical variables, and downstream analysis methods of ctDNA and summarizes its role across various clinical scenarios in CRC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"439"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription factor NFKB1 mediates TUBB6 to promote the proliferation and suppress apoptosis in glioma via Wnt/β-catenin signaling pathway.","authors":"Yan Li, Ziyu Shao, Jun Jiang, Hongyan Wang, Mei Zhang","doi":"10.1007/s12672-025-02268-x","DOIUrl":"10.1007/s12672-025-02268-x","url":null,"abstract":"<p><p>Glioma remains one of the most challenging brain tumors with poor prognosis. In this study, we aimed to elucidate the role of TUBB6 in glioma and its potential as a diagnostic and prognostic biomarker. Analysis of the GSE42656 and TCGA datasets revealed that TUBB6 was significantly upregulated in glioma tissues compared to normal tissues. The diagnostic value of TUBB6 was demonstrated with an area under the curve (AUC) of 0.702, suggesting that it could be used as a biomarker to differentiate gliomas Correlation analyses revealed that high TUBB6 expressions were associated with advanced WHO grades, IDH mutation status, and histological types of glioma. Further investigation identified NFKB1 as a key transcription factor that binds to the promoter region of TUBB6, upregulating its expression in glioma cells. Elevated levels of NFKB1 were associated with poor overall survival and disease-specific survival in glioma patients. Knockdown of NFKB1 resulted in reduced TUBB6 expression in glioma cells, confirming the regulatory roles of NFKB1 in TUBB6 expression. Prognostic analysis using TCGA and CGGA datasets demonstrated that high TUBB6 expression was associated with poorer overall survival (OS) and disease-specific survival (DSS) in glioma patients. TUBB6 was identified as an independent prognostic factor for both OS and DSS. Additionally, pan-cancer analysis revealed that TUBB6 was dysregulated in various tumor types and showed prognostic value across multiple cancers. Functional enrichment analysis of TUBB6-associated differentially expressed genes indicated involvement in immune response, extracellular matrix remodeling, and cytokine signaling pathways. In vitro experiments showed that TUBB6 knockdown suppressed glioma cell proliferation and promoted apoptosis by regulating the canonical Wnt/β-catenin signaling pathway. Our findings suggest that TUBB6 contributes to glioma malignancy through its effects on the Wnt/β-catenin pathway. In conclusion, TUBB6 emerges as a promising biomarker for glioma diagnosis and prognosis. Its regulation by NFKB1 and involvement in key signaling pathways underscore its potential as a therapeutic target for glioma treatment.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"444"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Appraising the causal role of cathepsins in genitourinary carcinoma: a two-sample mendelian randomization and prospective study based on 36,225 individuals.","authors":"Qiyu Zhu, Dingbang Liu, Haoyang Liu, Xiaohui Pan, Yifu Shi, Jingjing Guo, Nanwei Tong, Junru Chen, Hao Zeng","doi":"10.1007/s12672-025-02219-6","DOIUrl":"10.1007/s12672-025-02219-6","url":null,"abstract":"<p><strong>Background: </strong>Cathepsin family proteases play an important role in the carcinogenesis of genitourinary carcinomas. However, the causality between serum cathepsin levels and genitourinary carcinomas remains uninvestigated.</p><p><strong>Methods: </strong>In this study, we conducted a two-sample Mendelian Randomization (MR) analysis exploring the causal association between different types of cathepsins and genitourinary carcinomas. Univariate, bidirectional and multivariate MR analyses were conducted based on the genome-wide association studies. Moreover, linkage disequilibrium score regression (LDSC) analysis, colocalization and transcriptomic analysis were also performed. 36,225 Individual data from UK biobank was utilized for further validation.</p><p><strong>Results: </strong>Our findings revealed seven causal associations following univariate analysis, in which five correlations were further validated in multivariate analysis. Cathepsin S (CTSS) was positively associated with papillary renal cell carcinoma (pRCC) [IVW: OR (95%CI) 1.444 (1.103-1.890), p: 8*10-3], and LDSC analysis indicated a genetic correlation between CTSS and pRCC [rg (SE): 0.559 (0.225); p: 0.013]. Other causal correlations included cathepsin B (CTSB), positively associated with testicular non-seminoma, and cathepsin L2 (CTSL2/CTSV), negatively associated with overall kidney cancer and pRCC. Transcriptomic analysis further validated the findings from MR analysis. In the UK biobank, CTSL2 was found to be negatively associated with the risk of cancer of the kidney [HR (95%CI) 0.567 (0.368, 0.873), p: 0.01].</p><p><strong>Conclusions: </strong>Cathepsins played an important role in urogenital carcinogenesis. Further large-scale studies are warranted for extended validation.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"435"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}