Molecular Carcinogenesis最新文献_第6页

Improved Methods for the Stable Generation of Human Papillomavirus-Driven Head and Neck Cancer Cell Lines. 人乳头瘤病毒驱动的头颈部癌细胞系稳定生成的改进方法。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-12 DOI: 10.1002/mc.70025

Phuong N Le, Stephen B Keysar, Bettina Miller, J Jason Morton, Tugs-Saikhan Chimed, Nathaniel Alzofon, Cera Nieto, Kurtis D Davies, Carissa M Thomas, Alice N Weaver, Antonio Jimeno

引用次数: 0

HSC70 Promotes Breast Cancer Progression via PTEN Autophagic Degradation and PI3K/AKT/mTOR Activation. HSC70通过PTEN自噬降解和PI3K/AKT/mTOR激活促进乳腺癌进展。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-01 Epub Date: 2025-05-14 DOI: 10.1002/mc.23931

Zhengqi Wei, Beichen Xie, Xiangrui Meng, Keke Zhang, Hanyu Wei, Yu Gao, Changhua Liang, Hefei Chen

{"title":"HSC70 Promotes Breast Cancer Progression via PTEN Autophagic Degradation and PI3K/AKT/mTOR Activation.","authors":"Zhengqi Wei, Beichen Xie, Xiangrui Meng, Keke Zhang, Hanyu Wei, Yu Gao, Changhua Liang, Hefei Chen","doi":"10.1002/mc.23931","DOIUrl":"10.1002/mc.23931","url":null,"abstract":"Heat shock cognate protein 70 (HSC70) functions as a molecular chaperone and plays a crucial role in the regulation of intracellular protein modifications that are involved in tumor autophagy. However, its expression and mechanism in breast cancer have not been studied. The expression of HSC70 was verified by TCGA database and breast cancer patient tissue. We established breast cancer cell models and mouse models using knockdown HSC70. The expression and mechanism of HSC70 in breast cancer were investigated by immunocoprecipitation, protein stability, RNA stability, flow cytometry and biogenic analysis. In this study, we found that HSC70 is highly expressed in breast cancer and that high HSC70 expression positive correlated with poor prognosis using TCGA database and patient tissue verification. Subsequent experimental verification demonstrated that HSC70 drives cell cycle progression and promotes proliferation in breast cancer. Further studies revealed that HSC70 significantly promoted the phosphorylation of PI3K, AKT and mTOR but did not affect the total protein levels. Additionally, the AKT agonist SC79 reversed the effects of HSC70 knockdown on proliferation and cell cycle progression of breast cancer cells. Mechanistically, HSC70 reduces the protein stability of PTEN but does not change its mRNA level, suggesting that HSC70 binds to PTEN and promotes its autophagic degradation. More importantly, in vivo experiments demonstrated that HSC70 knockdown results in slower tumor proliferation and growth. In conclusion, HSC70 can bind to PTEN and promote its autophagic degradation, thereby activating the PI3K/AKT/mTOR signaling pathway to promote cell cycle progression and proliferation in breast cancer. These findings suggest that HSC70 may be a feasible target for breast cancer treatment.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1287-1301"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LINC02562 Promotes Progression of Lung Cancer by Regulating NTHL1 Dependent DNA Damage Repair Mechanisms. LINC02562通过调节NTHL1依赖的DNA损伤修复机制促进肺癌进展

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-01 Epub Date: 2025-06-11 DOI: 10.1002/mc.23935

Limian Cao, Hui Xu, Aijie Zhang, Lei Gao, Qianru Li, Jiaqi Yan, Chencheng Feng, Min Shao, Hao Gu

{"title":"LINC02562 Promotes Progression of Lung Cancer by Regulating NTHL1 Dependent DNA Damage Repair Mechanisms.","authors":"Limian Cao, Hui Xu, Aijie Zhang, Lei Gao, Qianru Li, Jiaqi Yan, Chencheng Feng, Min Shao, Hao Gu","doi":"10.1002/mc.23935","DOIUrl":"10.1002/mc.23935","url":null,"abstract":"Lung cancer poses a serious threat to public health due to its high morbidity and mortality rates. The mechanisms of lung cancer formation and progression are complex and involve regulation of various biomolecules. Long noncoding RNAs (lncRNAs) have emerged to be critical in tumorigenesis of various malignancies. In this study, we identified candidate lncRNAs associated with occurrence and development of lung cancer by analyzing the differentially expressed lncRNAs in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) cancer tissues and adjacent noncancerous tissues from UALCAN database. We found that LINC02562, which is highly expressed in LUAD and LUSC, can affect the occurrence and development of lung cancer in vivo and in vitro. Furthermore, LINC02562 competes with YBX1 to bind to the DNA repair protein NTHL1, which makes both the interaction between YBX1 and NTHL1, and the activity of NTHL1 in a balanced state, thereby promoting the progression of lung cancer. Additionally, the LINC02562/NTHL1/YBX1 axis represents a novel therapeutic target for lung cancer.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1362-1376"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SPP1⁺ Venous Endothelial Cells and CRABP2⁺ Tumor Cells Contribute to Favorable Body and Tail Pancreatic Ductal Adenocarcinoma Tumor Microenvironment. SPP1+静脉内皮细胞和CRABP2+肿瘤细胞有助于机体和尾部胰腺导管腺癌肿瘤微环境的形成

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-01 Epub Date: 2025-06-11 DOI: 10.1002/mc.23936

Yueze Liu, Yifan Fu, Tao Liu, Jun Wang, Zeyu Zhang, Yanan Shi, Zhe Cao, Gang Yang, Hao Chen, Wenhao Luo, Jinxin Tao, Yuanyang Wang, Guihu Weng, Menggang Zhang, Liyuan Ye, Jianchun Xiao, Jiangdong Qiu, Taiping Zhang, Hua Huang

{"title":"SPP1+ Venous Endothelial Cells and CRABP2+ Tumor Cells Contribute to Favorable Body and Tail Pancreatic Ductal Adenocarcinoma Tumor Microenvironment.","authors":"Yueze Liu, Yifan Fu, Tao Liu, Jun Wang, Zeyu Zhang, Yanan Shi, Zhe Cao, Gang Yang, Hao Chen, Wenhao Luo, Jinxin Tao, Yuanyang Wang, Guihu Weng, Menggang Zhang, Liyuan Ye, Jianchun Xiao, Jiangdong Qiu, Taiping Zhang, Hua Huang","doi":"10.1002/mc.23936","DOIUrl":"10.1002/mc.23936","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy; however, no validated treatments are currently available. Clinically, the tumor position, head and uncinate process (HU), or body and tail (BT) of the pancreas are vital for surgical strategies; however, fundamental research has seldom revealed the heterogeneous tumor microenvironment (TME) among different types of PDAC. Here, we applied multicohort single-cell and spatial RNA-seq methods together with patient-derived organoid models to reveal the TME heterogeneity between HU and BT PDAC. Osteopontin, encoded by SPP1, is secreted by vessel endothelial cells in BT PDAC and is associated with increased tumor burden. The number of tumor cells marked by CRABP2 was lower in BT PDAC and was identified as a prognostic marker of overall survival, as well as CD8+ T-cell infiltration. The expression of CRABP2 was also validated to be downregulated in BT PDAC in patient-derived organoid models. Overall, we profiled the heterogeneous PDAC TME between HU and BT PDAC, which could provide novel insight into the relationships between clinical characteristics and TME molecular research.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1377-1391"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Downregulation of HTRA1 Promotes EMT and Anoikis Resistance in Colorectal Cancer via Activation of Hippo/YAP1 Pathway by Facilitating LATS2 Degradation. HTRA1的下调通过促进LATS2降解激活Hippo/YAP1通路促进结直肠癌的EMT和Anoikis耐药。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-01 Epub Date: 2025-05-26 DOI: 10.1002/mc.23933

Zhihang Jiang, Xiaoqing Li, Fuqiang Liu, Junfeng Li, Kun Yang, Shuman Xu, Zheng Jiang

{"title":"Downregulation of HTRA1 Promotes EMT and Anoikis Resistance in Colorectal Cancer via Activation of Hippo/YAP1 Pathway by Facilitating LATS2 Degradation.","authors":"Zhihang Jiang, Xiaoqing Li, Fuqiang Liu, Junfeng Li, Kun Yang, Shuman Xu, Zheng Jiang","doi":"10.1002/mc.23933","DOIUrl":"10.1002/mc.23933","url":null,"abstract":"Epithelial-mesenchymal transition (EMT) and anoikis resistance are crucial characteristics for tumor cell metastasis. High-temperature requirement A1 (HTRA1) has been identified as a serine protease with chaperone functions, but its role in the regulation of EMT, anoikis resistance, and metastasis in colorectal cancer (CRC) remains poorly understood. In this study, we identified that HTRA1 was downregulated in CRC tissues, and its low expression was significantly associated with advanced TNM stage and poor prognosis. Loss of HTRA1 facilitated EMT and anoikis resistance in CRC cells, thereby potentiating metastatic potential both in vitro and in vivo. Conversely, HTRA1 overexpression produced opposite effects. Furthermore, we carried out RNA-seq and found that HTRA1 was probably involved in the regulation of Hippo/YAP1 pathway. HTRA1 overexpression led to increased phosphorylation of YAP1 and decreased nuclear translocation, which could be largely reversed by XMU-MP-1, an inhibitor of the Hippo pathway. Mechanistically, HTRA1 directly bound to and stabilized large tumor suppressor gene 2 (LATS2), a key kinase of the Hippo pathway, which contributed to the inactivation of YAP1. Restoring LATS2 expression in HTRA1-deficient CRC cells decreased EMT and anoikis resistance. Altogether, our findings unveiled the negative regulatory function of HTRA1 in CRC progression through the regulation of the Hippo/YAP1 pathway, and supported HTRA1 as a potential therapeutic target in CRC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1330-1346"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GRPEL2 Modulates Apoptosis in Esophageal Squamous Cell Carcinoma via the JNK Signaling Pathway. GRPEL2通过JNK信号通路调控食管鳞状细胞癌的凋亡。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-01 Epub Date: 2025-06-11 DOI: 10.1002/mc.23934

Lu Wen, Jiyu Pang, Jiaxin Yao, Rendan Zhang, Chunyan Zhao, Jiancai Tang, Chenwu Yang, Qin Liu, Jinyue Ma, Min Zhang, Bo Mu

{"title":"GRPEL2 Modulates Apoptosis in Esophageal Squamous Cell Carcinoma via the JNK Signaling Pathway.","authors":"Lu Wen, Jiyu Pang, Jiaxin Yao, Rendan Zhang, Chunyan Zhao, Jiancai Tang, Chenwu Yang, Qin Liu, Jinyue Ma, Min Zhang, Bo Mu","doi":"10.1002/mc.23934","DOIUrl":"10.1002/mc.23934","url":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide with a low survival rate due to a lack of therapeutic targets. Here we found that the mitochondria-related gene GrpE-like 2 (GRPEL2) transcript levels are significantly upregulated in ESCC patient samples, and its high expression predicts poor prognosis. Knockdown of GRPEL2 aggravated suppressed cell proliferation and colony formation. Conversely, overexpression of GRPEL2 promotes ESCC cell proliferation both In Vitro and In Vivo. We delved deeper into the effects of GRPEL2 on mitochondrial function and found that the depletion of GRPEL2 induced mitochondrial dysfunction and cellular apoptosis. Mechanistically, our RNA-Seq analysis revealed that suppression of GRPEL2 expression triggers activation of the MAPK/JNK signaling pathway. Additionally, the apoptosis induced by GRPEL2 loss can be largely reversed by treatment with SP600125, a JNK inhibitor. To further enhance the feasibility of targeting GRPEL2 for inhibiting ESCC proliferation in practical applications, we conducted computer-based drug screening to identify potential GRPEL2 inhibitors. We identified Vandetanib, a known antitumor agent, as a promising molecule that not only exhibits robust binding activity but also effectively reduces GRPEL2 protein levels. In conclusion, the data presented herein implicate GRPEL2 as a pivotal regulator in ESCC, modulating the MAPK/JNK signaling cascade to potentiate apoptosis, thereby offering a specific therapeutic vulnerability for targeting ESCC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1347-1361"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Transcriptional Variant of Anaplastic Lymphoma Kinase Promotes Apoptosis in Ovarian High-Grade Serous Carcinoma. 间变性淋巴瘤激酶的转录变异促进卵巢高级别浆液性癌的细胞凋亡。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-01 Epub Date: 2025-05-19 DOI: 10.1002/mc.23928

Ako Yokoi, Daigo Yoshimori, Yasuko Oguri, Miki Hashimura, Makoto Saegusa

{"title":"A Transcriptional Variant of Anaplastic Lymphoma Kinase Promotes Apoptosis in Ovarian High-Grade Serous Carcinoma.","authors":"Ako Yokoi, Daigo Yoshimori, Yasuko Oguri, Miki Hashimura, Makoto Saegusa","doi":"10.1002/mc.23928","DOIUrl":"10.1002/mc.23928","url":null,"abstract":"The current study aims to delineate the role of a novel anaplastic lymphoma kinase (ALK) transcript, ALKATI, in ovarian high-grade serous carcinoma (HGSC). Overexpressed ALKATI exhibited both cytoplasmic and nuclear localization in HGSC cells, whereas full-length ALK was predominantly cytoplasmic. ALKATI interacts with the DNA repair protein, poly (ADP ribose) polymer 1 (PARP1), and cells stably overexpressing ALKATI (OE- ALKATI) were more sensitive to cisplatin-induced apoptosis. Consistent with this, cleaved PARP1 levels were higher in HGSC tissue samples in areas with nuclear ALK immunoreactivity. The ratio of antiapoptotic BCL2 relative to proapoptotic BAX was significantly increased in OE-ALKATI cells, despite the increase in apoptosis, suggesting that ALKATI-mediated apoptosis is independent of mitochondrion-driven cell death. OE-ALKATI decreased epithelial-mesenchymal transition/cancer stem cell properties but did not alter proliferation rates, and nuclear ALK immunopositivity was not associated with clinicopathological factors or prognosis in HGSC. Together, our observations suggest that ALKATI sensitizes HGSC cells to apoptosis (probably though an association with PARP1) but this may have a relatively minor impact on tumor progression.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1283-1288"},"PeriodicalIF":3.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HPV16 CpG Methylation Contributes to Cervical Carcinogenesis by Regulating HPV16 Tumorigenesis-Related Genes. HPV16 CpG甲基化通过调控HPV16肿瘤发生相关基因参与宫颈癌发生

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-01 Epub Date: 2025-05-15 DOI: 10.1002/mc.23926

Yuanjing Lyu, Meng Cui, Nan Hu, Xiao Zheng, Li Song, Caihong Wu, Ruixin Pei, Ling Ding, Jintao Wang

{"title":"HPV16 CpG Methylation Contributes to Cervical Carcinogenesis by Regulating HPV16 Tumorigenesis-Related Genes.","authors":"Yuanjing Lyu, Meng Cui, Nan Hu, Xiao Zheng, Li Song, Caihong Wu, Ruixin Pei, Ling Ding, Jintao Wang","doi":"10.1002/mc.23926","DOIUrl":"10.1002/mc.23926","url":null,"abstract":"HPV16 CpG methylation is associated with cervical carcinogenesis and the expression of HPV16 tumorigenesis-related genes. However, the genome-wide methylation profile of HPV16 CpG sites during cervical carcinogenesis has not been fully characterized, and the regulatory role of HPV16 CpG methylation in the expression of these genes in cervical carcinogenesis remains unclear. This study aims to comprehensively map HPV16 CpG methylation patterns across different cervical carcinogenesis stages and elucidate its regulatory effect on the expression of HPV16 tumorigenesis-related genes as well as biological alterations in cervical cancer cells. A total of 341 participants diagnosed with various stages of cervical lesions and normal cervix were enrolled to evaluate the associations between HPV16 CpG methylation, expression of HPV16 tumorigenesis-related genes, and cervical carcinogenesis. Demethylation of HPV16 CpG sites in Caski cells using 5-Aza-dC was performed to assess subsequent changes in the expression of HPV16 tumorigenesis-related genes and cellular biological functions. HPV16 hypermethylation was associated with an increased risk of cervical cancer and precancerous lesions. Thirty-six specific CpG sites across various regions of the HPV16 genome exhibited progressively elevated methylation levels correlating with lesion severity. Effects of HPV16 CpGs methylation on cervical carcinogenesis were partially mediated by HPV16 oncoproteins. Demethylation of HPV16 CpGs significantly suppressed HPV16 oncogene expression, promoted apoptosis, and inhibited proliferation, migration, and invasion in cervical cancer cells. This study provides novel insights into the role of HPV16 CpG methylation in cervical carcinogenesis through the modulation of HPV16 oncogenes. This might represent a promising therapeutic strategy for impeding cervical cancer progression.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1302-1315"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reduced JAG1 Expression Through miR-200 Overexpression or Crispr-Cas Mediated Knockout Impairs TNBC Growth and Metastasis. 通过miR-200过表达或Crispr-Cas介导的敲除降低JAG1表达损害TNBC的生长和转移。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-01 Epub Date: 2025-06-11 DOI: 10.1002/mc.23937

Megan Vaz, Katrina L Watson, Roger A Moorehead

引用次数: 0

Causal Relationship Between Blood Metabolites and Prostate Cancer Risk: A Two-Sample Mendelian Randomization Study. 血液代谢物与前列腺癌风险的因果关系：一项双样本孟德尔随机研究。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-01 Epub Date: 2025-05-19 DOI: 10.1002/mc.23929

Shuai Liu, Jingjing Zhu, Huizhen Zhang, Hua Zhong, Hoi Tung Hilton Wong, Liang Wang, Lang Wu

{"title":"Causal Relationship Between Blood Metabolites and Prostate Cancer Risk: A Two-Sample Mendelian Randomization Study.","authors":"Shuai Liu, Jingjing Zhu, Huizhen Zhang, Hua Zhong, Hoi Tung Hilton Wong, Liang Wang, Lang Wu","doi":"10.1002/mc.23929","DOIUrl":"10.1002/mc.23929","url":null,"abstract":"Recent research has increasingly suggested an association between changes in specific blood metabolites and prostate cancer (PCa) development. However, it remains unclear whether these observed associations represent a causal relationship. To reveal the potential causal associations between blood metabolites and PCa risk, we conducted a comprehensive two-sample Mendelian randomization (MR) analysis. We used genetic instruments for 514 and 490 metabolites from two independent comprehensive genome-wide association studies. These studies included 14,295 individuals of European ancestry from the INTERVAL/EPIC-Norfolk cohorts and 8299 individuals of European ancestry from the Canadian Longitudinal Study on Aging cohort. Summary statistics of PCa risk involving 122,188 cases and 604,640 controls of European ancestry individuals were analyzed. The associations between metabolites and PCa risk were evaluated using the inverse-variance weighted method, supplemented by sensitivity analyses including MR-Egger and MR-PRESSO tests. Additionally, we conducted a phenome-wide MR analysis to assess the potential side effects of targeting the identified metabolites for PCa intervention. Our analysis revealed 107 unique blood metabolites significantly associated with PCa risk, with 43 of these associations consistently replicated using instruments from two independent data sets. This study provides novel insights into the potential role of specific metabolites in the etiology of PCa, which warrants further investigations.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1316-1329"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0