Carcinogenesis最新文献_第5页

Epigenetic mechanisms underlying endometrial cancer outcomes: race-specific patterns of DNA methylation associated with molecular subtypes and survival. 子宫内膜癌（EC）预后的表观遗传机制：与分子亚型和生存相关的DNA甲基化的种族特异性模式

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgaf004

Emery Hoos, Lauren E Koval, David L Corcoran, Lauren A Eaves, Kyle Roell, Julia E Rager, Xianming Tan, Sherette Godfrey, Temitope O Keku, Victoria Bae-Jump, Andrew F Olshan, Hazel B Nichols, Bernard E Weissman, Rebecca C Fry

{"title":"Epigenetic mechanisms underlying endometrial cancer outcomes: race-specific patterns of DNA methylation associated with molecular subtypes and survival.","authors":"Emery Hoos, Lauren E Koval, David L Corcoran, Lauren A Eaves, Kyle Roell, Julia E Rager, Xianming Tan, Sherette Godfrey, Temitope O Keku, Victoria Bae-Jump, Andrew F Olshan, Hazel B Nichols, Bernard E Weissman, Rebecca C Fry","doi":"10.1093/carcin/bgaf004","DOIUrl":"10.1093/carcin/bgaf004","url":null,"abstract":"Endometrial cancer (EC) is the fourth most common cancer in women in the USA. Stark racial disparities are present in EC outcomes in which Black women have significantly higher EC-related mortality than White women. The social and biologic factors that contribute to these disparities are complex and may include racial differences in epigenetic landscapes. To investigate race-specific epigenetic differences in EC tumor characteristics and outcomes, we utilized the most recent data within the Cancer Genome Atlas (TCGA). Genome-wide CpG methylation data for more than 850 000 CpG sites were analyzed across 245 tumor samples, including 52 from Black women and 181 from White women. Race-adjusted and race-stratified associations among CpG methylation in ECs and molecular subtypes and disease-free survival were examined. Race-specific analysis identified subtype-associated CpGs within 9572 genes in tumors from White women and only 10 genes in tumors that were from Black women. Race-specific analyses also identified survival-associated CpGs with 1119 unique genes identified in tumors from White women and none identified in tumors from Black women. Genes identified with differential methylation among subtypes included those involved in oxidative stress (HIF3A), and DNA repair (MLH1). Data from a replication cohort highlighted genes overlapping with those identified within the TCGA, such as G Protein Subunit Beta 1 (GNB1), involved in G-protein signaling, and Interleukin 37 (IL37), involved in cytokine signaling. Identification of these racial differences in EC tumor epigenetic landscapes and associated changes in gene expression may provide insight into strategies to improve outcomes and reduce disparities.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Elevated expression of Golgi Transport 1B promotes the progression of cervical cancer by activating the NF-kappaB signaling pathway via interaction with TANK-Binding Kinase 1. 高尔基体转运 1B 通过与 TBK1 相互作用激活 NF-κB 信号通路，从而促进宫颈癌的进展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae054

Yixuan Sun, Qihua Peng, Ruiwen Wang, Yifan Yin, Musitaba Mutailifu, Lipeng Hu, Yincheng Teng, Yang Zhou

{"title":"Elevated expression of Golgi Transport 1B promotes the progression of cervical cancer by activating the NF-kappaB signaling pathway via interaction with TANK-Binding Kinase 1.","authors":"Yixuan Sun, Qihua Peng, Ruiwen Wang, Yifan Yin, Musitaba Mutailifu, Lipeng Hu, Yincheng Teng, Yang Zhou","doi":"10.1093/carcin/bgae054","DOIUrl":"10.1093/carcin/bgae054","url":null,"abstract":"As a preventable disease, cervical cancer (cervical squamous cell carcinoma and endocervical adenocarcinoma-CESC) remains a tumor with high morbidity and mortality worldwide, underscoring the pressing need for effective treatment strategies. This research identified Golgi transport 1B (GOLT1B) as a critical gene involved in the development of cervical cancer. Gene Expression Omnibus (GEO) datasets were investigated to determine the upregulation of GOLT1B in cervical cancer tissue compared with normal tissue. Besides, GOLT1B was found to predict poor prognosis in cervical cancer by utilizing Gene Expression Profiling Interactive Analysis (GEPIA). The functional assay indicated that GOLT1B promoted CESC viability and migration in vitro and in vivo. RNA sequencing results suggested that GOLT1B likely influenced the nuclear factor-kappaB (NF-κB) pathway. The subsequent western blot and dual luciferase reporter assay revealed the interaction between GOLT1B and TANK binding kinase 1 (TBK1), modulating the NF-κB pathway. More importantly, GOLT1B was also found to regulate immune cell infiltration, suggesting its potential role in the tumor microenvironment. In conclusion, GOLT1B promotes CESC progression via interaction with TBK1 and augmentation of NF-κB signaling-mediated cancer-associated inflammation, which provides us with a new approach to CESC target therapy.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Novel inhibitory effect of Omega-3 fatty acids regulating pancreatic cancer progression. Omega-3脂肪酸调节胰腺癌进展的新抑制作用。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae081

María I Garay, Tamara Mazo, Victoria Ferrero, Nelso N Barotto, Clarisa Lagares, María F Granton, María J Moreira-Espinoza, David C Cremonezzi, Andrea Comba, Mabel N Brunotto, Ezequiel J Tolosa, Martín E Fernandez-Zapico, María E Pasqualini

{"title":"Novel inhibitory effect of Omega-3 fatty acids regulating pancreatic cancer progression.","authors":"María I Garay, Tamara Mazo, Victoria Ferrero, Nelso N Barotto, Clarisa Lagares, María F Granton, María J Moreira-Espinoza, David C Cremonezzi, Andrea Comba, Mabel N Brunotto, Ezequiel J Tolosa, Martín E Fernandez-Zapico, María E Pasqualini","doi":"10.1093/carcin/bgae081","DOIUrl":"10.1093/carcin/bgae081","url":null,"abstract":"Pancreatic cancer is a devastating malignancy in great need of new and more effective treatment approaches. In recent years, studies have indicated that nutritional interventions, particularly nutraceuticals, may provide novel avenues to modulate cancer progression. Here, our study characterizes the impact of ω-3 polyunsaturated fatty acids, eicosapentaenoic acid, and docosahexaenoic acid, as a nutraceutical intervention in pancreatic cancer using a genetically engineered mouse model driven by KrasG12D and Trp53R172H. This model closely resembles human pancreatic carcinogenesis, offering a disease relevant platform for translational research. Our findings showed that ω-3 polyunsaturated fatty acids intervention (using a diet supplemented with 6% cod liver oil) significantly reduced tumor volume as well as lung and liver metastasis and a trend toward improved survival rate compared with control treated mice. This antitumoral effect was accompanied by distinct changes in tumor membrane fatty acid profile and eicosanoids release. Furthermore, the eicosapentaenoic acid and docosahexaenoic acid intervention also reduced malignant histological parameters and induced apoptosis without affecting cell proliferation. Of note is the significant reduction in tumor fibrosis that was associated with decreased levels of Sonic Hedgehog, a major ligand controlling this cellular compartment in pancreatic cancer. All together our results demonstrate the impact of eicosapentaenoic acid and docosahexaenoic acid as antitumor regulators in pancreatic cancer, suggesting potential for ω-3 polyunsaturated fatty acids as a possible antitumoral dietary intervention. This research opens new avenues for integrating nutraceutical strategies in pancreatic cancer management.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12097994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Prognostic value of circulating tumor DNA in different cancer types detected by ultra-low-pass whole-genome sequencing: a systematic review and patient-level survival data meta-analysis. 通过超低通量全基因组测序检测不同癌症类型中循环肿瘤DNA的预后价值。系统综述和患者生存数据荟萃分析。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae073

Miguel Sogbe, Daniel Aliseda, Paloma Sangro, Manuel de la Torre-Aláez, Bruno Sangro, Josepmaria Argemi

{"title":"Prognostic value of circulating tumor DNA in different cancer types detected by ultra-low-pass whole-genome sequencing: a systematic review and patient-level survival data meta-analysis.","authors":"Miguel Sogbe, Daniel Aliseda, Paloma Sangro, Manuel de la Torre-Aláez, Bruno Sangro, Josepmaria Argemi","doi":"10.1093/carcin/bgae073","DOIUrl":"10.1093/carcin/bgae073","url":null,"abstract":"Ultra-low-pass whole-genome sequencing (ULP-WGS) (≤0.5 × coverage) of plasma cell-free DNA (cfDNA) has emerged as a low-cost, promising tool to assess the circulating tumor DNA (ctDNA) fraction. This meta-analysis aims to summarize the current findings and comprehensively investigate the prognostic value of baseline ctDNA detected by ULP-WGS in solid tumors. A systematic review was carried out by searching PubMed/MEDLINE and Scopus databases to identify eligible studies conducted between January 2014 and January 2024. Inclusion criteria comprised studies with reported overall survival and progression-free survival outcomes across therapy-naïve patients with different solid tumors. All patients underwent baseline ULP-WGS of plasma cfDNA and were categorized as ctDNA positive (tumor fraction ≥10%) or negative (tumor fraction <10%). A one-stage meta-analysis was performed using patient-level survival data reconstructed from published articles. A Cox proportional hazards model with shared frailty was used to assess the difference in survival between arms. A total of six studies, comprising 620 patients (367 negative ctDNA and 253 positive ctDNA), were included in the overall survival analysis, while five studies, involving 349 patients (212 negative ctDNA and 137 positive ctDNA), were included in the progression-free survival analysis. The meta-analysis showed that patients with baseline positive ctDNA had a significantly higher risk of death (HR = 2.60, 95% CI: 2.01-3.36) and disease progression (HR = 2.28, 95% CI: 1.71-3.05) compared to those with negative ctDNA. The presence of a positive ctDNA at baseline is associated with increased risk of death and progression in patients with same-stage cancer.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Copper in colorectal cancer patients: a systematic review and meta-analysis. 铜在结直肠癌患者中的作用：一项系统综述和荟萃分析。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgaf001

Carlos Muñoz-Bravo, Inés Marín-Burdallo, Lucas González-Herrera, Carla González-Palacios Torres, Macarena Lozano-Lorca, José Juan Jiménez-Moleón, Rocío Olmedo-Requena

{"title":"Copper in colorectal cancer patients: a systematic review and meta-analysis.","authors":"Carlos Muñoz-Bravo, Inés Marín-Burdallo, Lucas González-Herrera, Carla González-Palacios Torres, Macarena Lozano-Lorca, José Juan Jiménez-Moleón, Rocío Olmedo-Requena","doi":"10.1093/carcin/bgaf001","DOIUrl":"10.1093/carcin/bgaf001","url":null,"abstract":"Several clinical studies have evaluated the relationship between copper on colorectal cancer (CRC), but the results are contradictory. This study aimed to conduct a systematic review and meta-analysis to investigate copper measured in two biological matrices (serum/plasma/blood and tissue) and dietary intake in CRC patients compared to healthy controls. We conducted a comprehensive and systematic search in PubMed, Scopus, Embase, and Web of Science. We included studies that reported copper levels in serum/plasma/blood, tissue, or from the diet, with an observational study design (cohort and case-control studies). Study quality was assessed with the Newcastle-Ottawa scale and potential causes of heterogeneity were evaluated. Standardized mean differences (SMD) with 95% confidence interval (CI) were pooled using random-effect models. Overall pooled odds ratio and 95% CI for the risk of CRC were calculated. Twenty-six studies (23 case-control and 3 cohort studies) with a total of 227 354 participants were included. Most of the studies presented low (50%) or moderate quality (42.3%). No differences in serum/plasma/blood copper levels (SMD = 0.23; 95% CI: -0.23, 0.70; I2 = 97.3%, 19 studies), tissue copper levels (SMD = -1.69; 95% CI: -3.41, 0.03; I2 = 85.6%, 2 studies), or copper/zinc ratio (SMD = 1.19; 95% CI: 0.54, 1.84; I2 = 95.3%, 6 studies) were found between CRC patients and healthy controls. Regarding dietary copper, CRC patients had a lower intake (SMD = -0.27; 95% CI: -0.51, -0.03; I2 = 0.0%, 2 studies). No differences were found in copper levels between CRC patients and healthy controls. However, evidence shows mostly low or moderate quality, and results were heterogeneous. More prospective studies with an adequate methodological approach are needed.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Antibody-drug conjugates in breast cancer. 乳腺癌中的抗体-药物偶联物。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae082

Yinxing Zhu, Yaqi Song, Xilei Zhou, Wenwen Zhang, Honglei Luo

引用次数: 0

HuR/miR-124-3p/VDR complex bridges lipid metabolism and tumor development in colorectal cancer. HuR/miR-124-3p/VDR复合物是结直肠癌脂质代谢和肿瘤发生的桥梁。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae061

Fengxing Huang, Luping Bu, Mengting Li, Youwei Wang, Runan Zhang, Yu Shao, Kun Lin, Hong Yang, Qiu Zhao, Lan Liu

{"title":"HuR/miR-124-3p/VDR complex bridges lipid metabolism and tumor development in colorectal cancer.","authors":"Fengxing Huang, Luping Bu, Mengting Li, Youwei Wang, Runan Zhang, Yu Shao, Kun Lin, Hong Yang, Qiu Zhao, Lan Liu","doi":"10.1093/carcin/bgae061","DOIUrl":"10.1093/carcin/bgae061","url":null,"abstract":"Maintaining a balanced lipid status to prevent lipotoxicity is of paramount importance in various tumors, including colorectal cancer (CRC). HuR, an RNA-binding protein family member, exhibits high expression in many cancers possibly because it regulates cell proliferation, migration, invasion, and lipid metabolism. However, the role of HuR in the regulation of abnormal lipid metabolism in CRC remains unknown. We found that HuR promotes vitamin D receptor (VDR) expression to ensure lipid homeostasis by increasing triglyceride (TG) and total cholesterol (TC) levels in CRC, thus confirming the direct binding of an overexpressed HuR to the CDS and 3'-UTR of Vdr, enhancing its expression. Concurrently, HuR can indirectly affect VDR expression by inhibiting miR-124-3p. HuR can suppress the expression of miR-124-3p, which binds to the 3'-UTR of Vdr, thereby reducing VDR expression. Additionally, a xenograft model demonstrated that targeting HuR inhibits VDR expression, blocking TG and TC formation, and hence mitigating CRC growth. Our findings suggest a regulatory relationship among HuR, miR-124-3p, and VDR in CRC. We propose that the HuR/miR-124-3p/VDR complex governs lipid homeostasis by impacting TG and TC formation in CRC, offering a potential therapeutic target for CRC prevention and treatment.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Yes-associated protein plays oncogenic roles in human sporadic colorectal adenomas. yes相关蛋白（YAP）在人类散发性结直肠腺瘤中起致瘤作用。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgaf007

Lei Fan, Xingyi Guo, Mary K Washington, Jiajun Shi, Reid M Ness, Qi Liu, Wanqing Wen, Shuya Huang, Xiao Liu, Qiuyin Cai, Wei Zheng, Robert J Coffey, Martha J Shrubsole, Timothy Su

{"title":"Yes-associated protein plays oncogenic roles in human sporadic colorectal adenomas.","authors":"Lei Fan, Xingyi Guo, Mary K Washington, Jiajun Shi, Reid M Ness, Qi Liu, Wanqing Wen, Shuya Huang, Xiao Liu, Qiuyin Cai, Wei Zheng, Robert J Coffey, Martha J Shrubsole, Timothy Su","doi":"10.1093/carcin/bgaf007","DOIUrl":"10.1093/carcin/bgaf007","url":null,"abstract":"The role of Hippo-Yes-associated protein (YAP) in human colorectal cancer (CRC) presents contradictory results. We examined the function of YAP in the early stages of CRC by quantitatively measuring the expression of phospho-YAPS127 (p-YAP) and five APC-related proteins in 145 sporadic adenomas from the Tennessee Colorectal Polyp Study, conducting APC sequencing for 114 adenomas, and analyzing YAP-correlated cancer pathways using gene expression data from 326 adenomas obtained from Gene Expression Omnibus. The p-YAP expression was significantly correlated with YAP expression (r = 0.53, P < .0001) and nuclear β-catenin (r = 0.26, P = .0018) in adenoma tissues. Both p-YAP and nuclear β-catenin were associated with APC mutations (P = .05). A strong association was observed between p-YAP overexpression and advanced adenoma odds (OR = 12.62, 95% CI = 4.57-34.86, P trend < .001), which persisted after adjusting for covariates and biomarkers (OR = 12.31, 95% CI = 3.78-40.10, P trend < .0001). P-YAP exhibited a sensitivity of 77.4% and specificity of 78.2% in defining advanced versus nonadvanced adenomas. Additionally, synergistic interaction was noted between p-YAP positivity and nuclear β-catenin on advanced adenomas (OR = 16.82, 95% CI = 4.41-64.08, P < .0001). YAP-correlated genes were significantly enriched in autophagy, unfolded protein response, and sirtuin pathways showing predominantly pro-tumorigenic alterations. Collectively, YAP plays an oncogenic role in interacting with Wnt as well as other cancer pathways within human sporadic adenomas. P-YAP could be a potential biomarker for human high-risk sporadic adenomas.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Germline alteration analysis reveals EPHB4R91H mutation as a key player in multiple primary lung tumors. 种系畸变分析揭示 EPHB4R91H 突变是多种原发性肺肿瘤的关键因素

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae074

Jing Li, Yanan Li, Xinjuan Wang, Zhigang Zhou, Xiangnan Li, Songwei Yue, Huaqi Wang, Ming Yang, Guojun Zhang

{"title":"Germline alteration analysis reveals EPHB4R91H mutation as a key player in multiple primary lung tumors.","authors":"Jing Li, Yanan Li, Xinjuan Wang, Zhigang Zhou, Xiangnan Li, Songwei Yue, Huaqi Wang, Ming Yang, Guojun Zhang","doi":"10.1093/carcin/bgae074","DOIUrl":"10.1093/carcin/bgae074","url":null,"abstract":"Multiple primary lung tumors are garnering attention from clinicians, with adenocarcinoma emerging as the predominant histological type. Because of the heterogeneity and diffuse distribution of lesions in the same patient, the treatment of multiple primary lung adenocarcinoma (MPLA) is a significant challenge. As a kind of variation unaffected by tumor heterogeneity, germline alterations may play a key role in the development of MPLA. Here, whole-exome sequencing of peripheral blood was employed to obtain germline alteration data. Intergroup comparative analyses on rare and deleterious alterations of MPLA, solitary lung adenocarcinoma, and healthy individuals in an MPLA family were performed to clarify the candidate alterations. Whole-exome sequencing and targeted Sanger sequencing were performed in 27 disseminated MPLA patients to detect the mutation site that had been screened. A rare and deleterious germline alteration, EPHB4R91H, was found in all of the patients of an MPLA family and a patient with disseminated MPLA. It was revealed that EPHB4R91H was able to enhance the proliferation, migration, and invasion ability of A549 cells through increased binding affinity to ephrinB2, which in turn activated the EPHB4/ERK/JNK/MAPK pathway. Our findings corroborate that germline alterations are involved in the development of MPLA. And it was found for the first time that the EPHB4R91H mutation promotes the development of MPLA by enhancing its affinity for ephrinB2 and thereby active EPHB4/ERK/JNK/MAPK pathway.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

The role of interleukin 17 in cancer: a systematic review. 白细胞介素 17 (IL17) 在癌症中的作用：系统综述。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae079

Emir Begagic, Semir Vranic, Ajith Sominanda

引用次数: 0