Carcinogenesis最新文献

Integrated functional genomics-identified DEAF1 in oxidative stress and hepatocellular carcinoma development. 整合功能基因组学鉴定聋1在氧化应激和肝细胞癌发展中的作用。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-06-24 DOI: 10.1093/carcin/bgaf032

Linying Huang, Xinyuan Yu, Ziqi Zhang, Yanfei Huo, Long Zhang, Nasha Zhang, Ming Yang

{"title":"Integrated functional genomics-identified DEAF1 in oxidative stress and hepatocellular carcinoma development.","authors":"Linying Huang, Xinyuan Yu, Ziqi Zhang, Yanfei Huo, Long Zhang, Nasha Zhang, Ming Yang","doi":"10.1093/carcin/bgaf032","DOIUrl":"https://doi.org/10.1093/carcin/bgaf032","url":null,"abstract":"Hepatocellular carcinoma (HCC) is the third most common cause of death for cancer patients globally, with the overall 5-year survival rate of only 16%. The molecular mechanisms leading to malignant progression of HCC patients remain largely unclear. Hepatocyte nuclear factor 4α (HNF4α) functions as a tumor suppressive transcription factor (TF) in HCC. In this study, we aimed to identify functional HCC susceptibility single nucleotide polymorphisms (SNPs) in HNF4α-binding sites throughout the human genome. We identified 1,274 HNF4α-binding site polymorphisms via a genome-wide screening using TUIFGA (The Updated Integrative Functional Genomics Approach) which we previously developed to recognize cancer susceptibility SNPs within genome-wide TF-binding sites. Among these SNPs, the DEAF1 rs11246280 SNP was significantly associated with HBV-related HCC susceptibility in several case-control studies. Importantly, the rs11246280 SNP could interrupt HNF4α-binding to the DEAF1 promoter and enhance DEAF1 expression. Oncogenic TF DEAF1 binds to the SLC38A3 promoter, elevates glutamine transporter SLC38A3 expression, enhances influx of glutamine and GSH production, leads to reduced ROS levels in cells and, thereby, promotes HCC progression. Our findings highlighted the role of DEAF1 during HCC development via maintaining redox balance, which sheds light on the development of novel cancer therapeutics.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483243","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

Urinary Metabolites in Association with Kidney Cancer Risk. 尿代谢产物与肾癌风险的关系

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-06-18 DOI: 10.1093/carcin/bgaf029

Thuraya Al-Sayegh, Shuang Song, Loren Lipworth, Hui Cai, Qing Lan, Yutang Gao, Nathaniel Rothman, Qiuyin Cai, Wei Zheng, Xiao-Ou Shu

{"title":"Urinary Metabolites in Association with Kidney Cancer Risk.","authors":"Thuraya Al-Sayegh, Shuang Song, Loren Lipworth, Hui Cai, Qing Lan, Yutang Gao, Nathaniel Rothman, Qiuyin Cai, Wei Zheng, Xiao-Ou Shu","doi":"10.1093/carcin/bgaf029","DOIUrl":"https://doi.org/10.1093/carcin/bgaf029","url":null,"abstract":"Kidney cancer incidence has increased worldwide in recent decades. While metabolomic studies have shown promise in unveiling mechanisms underlying disease development, few studies have investigated pre-diagnostic urinary metabolites and kidney cancer risk. We conducted a case-control study nested within the Shanghai Women's and Men's Health Studies to prospectively investigate the association between urinary metabolites and kidney cancer risk to understand its etiology and the underlying biological mechanisms. Two hundred primary kidney cancer cases and their individually matched controls were included. A total of 1,301 metabolites were evaluated, and 67 metabolites were found nominally associated with kidney cancer using conditional logistic regression. After backward selection, eleven urine metabolites remained significantly associated with kidney cancer: lipids (e.g., picolinoylglycine, odds ratio (OR); 95% confidence interval (CI): 2.01 [1.44, 2.79], and pregnanediol-3-glucuronide, OR; 95% CI: 0.56 [0.39, 0.82]), xenobiotics (e.g., beta-guanidinopropanoate, OR; 95% CI: 1.75 [1.32, 2.32] and 4-vinylphenol sulfate, OR; 95% CI: 0.66 [0.49, 0.90]), and nucleotides (e.g., allantoic acid, OR; 95% CI: 0.71 [0.54, 0.92]). Time lag analysis showed that metabolite-kidney cancer associations were stronger for beta-guanidinopropanoate (OR; 95%CI: 8.22 [1.68, 40.18]) and picolinoylglycine (OR; 95% CI: 6.45[1.28, 32.43]), but weaker for allantoic acid (OR; 95%CI: 0.87 [0.37, 2.06]) and 3-methylglutarate/2-methylglutarate (OR; 95%CI: 0.62 [0.19, 2.00]) when urinary samples were collected within 3 years between urine sample collection and cancer diagnosis (Pinteraction <0.05 for all). Future metabolomics studies with large sample sizes, particularly from multiple ancestry populations, are needed to validate our findings.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504895","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

Identification of HCAR1 as a ferroptosis-related biomarker of gastric cancer based on a novel ferroptosis-related prognostic model and in vitro experiments. 基于新型吸铁相关预后模型和体外实验的HCAR1作为胃癌吸铁相关生物标志物的鉴定

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-06-07 DOI: 10.1093/carcin/bgaf030

Hongjiao Zhang, Jinbo Zhan, Juanjuan Zhou, Liping Liu, Yan He, Yi Le, Weiqi Liu, Ling Zhou, Yawen Liu, Xiaojun Xiang

{"title":"Identification of HCAR1 as a ferroptosis-related biomarker of gastric cancer based on a novel ferroptosis-related prognostic model and in vitro experiments.","authors":"Hongjiao Zhang, Jinbo Zhan, Juanjuan Zhou, Liping Liu, Yan He, Yi Le, Weiqi Liu, Ling Zhou, Yawen Liu, Xiaojun Xiang","doi":"10.1093/carcin/bgaf030","DOIUrl":"https://doi.org/10.1093/carcin/bgaf030","url":null,"abstract":"Currently, research on ferroptosis-related prognostic models for gastric cancer is limited, whereas traditional predictive models often have a narrow perspective and low accuracy. In this study, we systematically analyzed the expression patterns of ferroptosis-related genes in patients with gastric adenocarcinoma and evaluated their prognostic value. Using data from The Cancer Genome Atlas (TCGA) and the FerrDb database, we developed a ferroptosis-related prognostic risk model based on four genes: hydroxycarboxylic acid receptor 1 (HCAR1), branched-chain amino acid transaminase 1 (BCAT1), ceruloplasmin (CP), and dickkopf-1 (DKK1). This model demonstrated strong prognostic value and potential clinical relevance in stratifying gastric cancer patients by overall survival outcomes. ferroptosis-related prognostic risk model. Compared to traditional clinicopathological features, the risk score derived from this model exhibited superior predictive accuracy for overall survival in patients with gastric cancer and served as an independent prognostic factor. Functional enrichment analysis revealed that the risk score was primarily enriched for extracellular matrix-related pathways. Additionally, the risk score was significantly correlated with TME signature genes, immune checkpoint expression, and immune cell infiltration in stomach adenocarcinoma (STAD). Mechanistic studies revealed that HCAR1 is abnormally overexpressed in gastric cancer tissues and is associated with a poor prognosis. It exerted its effects by regulating the GPX4/SLC7A11 axis to inhibit lipid peroxidation and malondialdehyde accumulation, thereby obstructing ferroptosis. Experimental validation demonstrated that the downregulation of HCAR1 promoted ferroptosis and suppressed malignant tumor phenotypes, suggesting that both the gene and its associated risk model hold significant clinical value as potential therapeutic targets and prognostic biomarkers.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246612","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

Somatic p53 mutations that are markedly overrepresented in lung cancer confer resistance to ROS-induced cell death. 体细胞p53突变在肺癌中明显过度代表赋予ros诱导的细胞死亡的抗性。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-06-03 DOI: 10.1093/carcin/bgaf027

Mason A Tracewell, Jonathan E Karlin, Samantha M Barnada, Elizabeth L McDuffie, Charles P Scott, Julie A Barta, Steven B McMahon

{"title":"Somatic p53 mutations that are markedly overrepresented in lung cancer confer resistance to ROS-induced cell death.","authors":"Mason A Tracewell, Jonathan E Karlin, Samantha M Barnada, Elizabeth L McDuffie, Charles P Scott, Julie A Barta, Steven B McMahon","doi":"10.1093/carcin/bgaf027","DOIUrl":"https://doi.org/10.1093/carcin/bgaf027","url":null,"abstract":"Lung cancer is among the leading causes of cancer-related death in the U.S. Cigarette smoking remains the leading risk factor for lung cancer and can cause somatic mutations in the critical tumor suppressor gene TP53, among others. Mutations in TP53 not only cause loss of wild-type function but may also introduce oncogenic, gain-of-function (GOF) properties. The frequency of missense mutations at residues p.V157 and p.R158 in p53 increases dramatically in lung cancer relative to other cancers. These p53 mutants exhibit both loss of wild-type p53 function and GOF properties, including broadly rewiring gene expression programs in lung cancer cells. Several pan-cancer hotspot mutations in p53 impart GOF activities that reprogram cellular metabolism. To refine our understanding of the GOF properties conferred by the lung-enriched p53 mutants, the cellular metabolism of cells containing mutant p53 (V157F) was investigated. Untargeted metabolomics revealed that glutathione metabolism is among the top altered metabolic pathways related to mutant p53 (V157F). p53 mutants V157F and R158L provided resistance to oxidative stress induced by both menadione and cigarette smoke extract. The cell death experienced in the absence of mutant p53 (V157F; R158L) was due to the increase in reactive oxygen species (ROS). These findings suggest that the lung-enriched mutations in p53 (V157F; R158L) confer lung cancer cells with resistance to ROS, and ROS accumulation in the absence of mutant p53 causes cell death.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207814","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

The impact of reproductive factors on breast tumor and normal-adjacent tissue immune profile from menarche to menopause. 月经初潮至绝经期生殖因素对乳腺肿瘤及正常邻近组织免疫谱的影响。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-05-30 DOI: 10.1093/carcin/bgaf028

Cheng Peng, Yuxi Liu, Yujing J Heng, Clara Bodelon, Daniel Stover, Wendy Y Chen, Michelle D Holmes, A Heather Eliassen, Peter Kraft, Rulla M Tamimi

{"title":"The impact of reproductive factors on breast tumor and normal-adjacent tissue immune profile from menarche to menopause.","authors":"Cheng Peng, Yuxi Liu, Yujing J Heng, Clara Bodelon, Daniel Stover, Wendy Y Chen, Michelle D Holmes, A Heather Eliassen, Peter Kraft, Rulla M Tamimi","doi":"10.1093/carcin/bgaf028","DOIUrl":"https://doi.org/10.1093/carcin/bgaf028","url":null,"abstract":"Reproductive factors and sex hormones are tightly linked to systemic immunity. However, no studies have examined whether reproductive factors and hormone use modulate the immune microenvironment of breast tissue. We prospectively evaluated the associations of reproductive factors and exogenous hormone use with breast tumor and normal-adjacent tissue immune cell markers among 935 breast cancer cases in the Nurses' Health Studies. We deconvoluted immune cell abundance using CIBERSORTx and derived gene expression signatures of markers for immune checkpoint (PD1, PDL1, and CTLA4), co-regulatory signal and antigen presentation (MHC class I/ II and T cell receptor) and mammary cytokine signaling. Linear regression was used adjusting for confounders. Patterns of associations between reproductive factors and immune profile differed between tumor and normal-adjacent tissues and by estrogen receptor (ER) status. Tumors from post-menopausal women had significantly higher pro-inflammatory cytokine signaling and antigen presentation compared to tumors from pre-menopausal women (FDR≤0.05). Several reproductive factors were nominally associated with immune profiles of normal-adjacent tissues. For example, parous women had higher CD8 T cell infiltration, higher PDL1 expression, and lower cytokine signaling (p≤0.05); women who ever breastfed showed higher infiltration of NK cells and T helper cells in normal-adjacent tissue of ER+ tumors but lower infiltration of CD8 T cell and monocyte, and higher expression of cytokine signaling in normal-adjacent tissue of ER- tumors (p≤0.05). Our study demonstrates for the first time in a large epidemiologic study that reproductive factors may influence breast tumor immune microenvironment and sheds light on potential immune regulation for breast cancer prevention.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180754","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

Mechanisms of tumor-associated macrophages promoting tumor immune escape. 肿瘤相关巨噬细胞促进肿瘤免疫逃逸的机制。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-05-15 DOI: 10.1093/carcin/bgaf023

Shengfen Li, Mengxia Zhang, Yuan Gao, Can Zhao, Shuxian Liao, Xuhong Zhao, Qian Ning, Shengsong Tang

{"title":"Mechanisms of tumor-associated macrophages promoting tumor immune escape.","authors":"Shengfen Li, Mengxia Zhang, Yuan Gao, Can Zhao, Shuxian Liao, Xuhong Zhao, Qian Ning, Shengsong Tang","doi":"10.1093/carcin/bgaf023","DOIUrl":"https://doi.org/10.1093/carcin/bgaf023","url":null,"abstract":"The phenomenon of tumor immune escape involves multiple mechanisms that enable tumor cells to evade recognition and assault by the host's immune system, facilitating their survival and growth within the organism. Furthermore, tumor immune escape represents a critical mechanism in tumor progression and significantly contributes to the unsuccessful outcomes of immunotherapy. Tumor-associated macrophages (TAMs) are recruited into the tumor microenvironment (TME), serving a pivotal role in modulating tumor immune escape. An increasing body of research has demonstrated that TAMs are linked to unfavorable cancer prognosis and drug resistance. They suppress immune cell activity, hinder antigen presentation, and inhibit T cell activation, thereby helping tumor cells evade immune attacks. Consequently, elucidating the mechanisms by which TAMs promote tumor immune escape is crucial for developing novel immunotherapeutic strategies and improving the efficacy of cancer immunotherapy. In terms of clinical relevance, studies on TAMs have revealed their significant roles in various types of cancer. In recent years, transformational therapies such as CSF-1R inhibitors and CD40 agonists targeting TAMs have entered clinical trials and are expected to reverse immunosuppression and enhance immunotherapy response. These studies provide new directions for improving the effectiveness of existing immunotherapies and overcoming drug resistance.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076191","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

Chemoresistance and immune evasion in hepatocellular carcinoma: the role of miRNA-425-5p. 肝癌化疗耐药和免疫逃逸：miRNA-425-5p的作用。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf012

Xinghe Pan, Junliang Liu, Yitong Zhang, Chenglin Sun, You Li

{"title":"Chemoresistance and immune evasion in hepatocellular carcinoma: the role of miRNA-425-5p.","authors":"Xinghe Pan, Junliang Liu, Yitong Zhang, Chenglin Sun, You Li","doi":"10.1093/carcin/bgaf012","DOIUrl":"10.1093/carcin/bgaf012","url":null,"abstract":"Hepatocellular carcinoma (HCC) represents a significant global health challenge, with chemoresistance severely limiting treatment efficacy. This study investigates the role of miRNA-425-5p in exosomes in modulating the tumor microenvironment (TME) and contributing to chemoresistance and immune evasion in HCC. Differentially expressed miRNAs were identified using TaqMan low-density array technology in serum samples from XELOX-resistant and -sensitive HCC patients. miRNA-425-5p expression was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Exosomes from HCC cell lines were characterized by transmission electron microscopy and nanoparticle tracking analysis. Functional assays, including luciferase reporter assays and flow cytometry, elucidated the mechanisms of miRNA-425-5p. In vivo studies with mouse xenograft models evaluated the impact of miRNA-425-5p on tumor growth and chemosensitivity. miRNA-425-5p was significantly upregulated in the serum of XELOX-resistant HCC patients and correlated with poorer survival outcomes. Exosomes from chemoresistant HCC cells exhibited increased levels of miRNA-425-5p, which, when internalized by CD4+ T cells, promoted regulatory T cell (Treg) expansion by targeting phosphatase and tensin homolog (PTEN). In vivo, miRNA-425-5p overexpression enhanced tumor growth and chemoresistance, while its inhibition reduced tumor size and increased chemosensitivity. These findings indicate that miRNA-425-5p in exosomes plays a crucial role in HCC chemoresistance and immune evasion by modulating the TME and promoting Treg expansion through PTEN targeting. miRNA-425-5p serves as a potential biomarker for predicting chemoresistance and a therapeutic target for overcoming drug resistance in HCC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596387","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

LncRNA MEG3 suppresses prostate cancer progression by mediating macrophage polarization via the miR-148a-3p/ARRDC3 signaling axis. LncRNA MEG3通过miR-148a-3p/ARRDC3信号轴介导巨噬细胞极化抑制前列腺癌进展

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf009

Jinguang Luo, Huaixiang Tao, Long Chen, Hao Hu, Likai Mao, Han Guan

{"title":"LncRNA MEG3 suppresses prostate cancer progression by mediating macrophage polarization via the miR-148a-3p/ARRDC3 signaling axis.","authors":"Jinguang Luo, Huaixiang Tao, Long Chen, Hao Hu, Likai Mao, Han Guan","doi":"10.1093/carcin/bgaf009","DOIUrl":"10.1093/carcin/bgaf009","url":null,"abstract":"Long-chain noncoding RNA (LncRNA) MEG3 significantly influences tumor microenvironment (TME) dynamics and macrophage polarization. However, its specific involvement in prostate cancer (PCa) progression remains unclear. MEG3 exhibited low expression in PCa, and immune infiltration analysis revealed a positive association with M1 macrophages infiltration and a negative association with M2 macrophages infiltration. Immunohistochemical analysis demonstrated increased MEG3 levels, corresponding with upregulated INOS (an M1 marker) and downregulated CD163 (an M2 marker). MEG3 expression was markedly elevated in LPS-induced M1 macrophages and notably reduced in IL-4-induced M2 macrophages. The overexpression of MEG3 significantly enhanced M1 macrophages polarization while suppressing M2 macrophages polarization. Using an online database and a dual luciferase reporter assay, miR-148a-3p was identified as a downstream target of MEG3. Reduced miR-148a-3p expression was observed in LPS-induced M1 macrophages, while an increase was noted in IL-4-induced M2 macrophages. Moreover, MEG3 overexpression's impact on macrophage polarization was nullified following miR-148a-3p mimic transfection. ARRDC3 was validated as a downstream target of miR-148a-3p. The upregulation of ARRDC3 triggered by MEG3 overexpression was effectively suppressed by miR-148a-3p mimics. Additionally, Knockdown of ARRDC3 effectively counteracted the MEG3 overexpression-induced increase in M1 macrophages polarization while simultaneously mitigating the reduction in M2 macrophages polarization. Collectively, MEG3 exhibits reduced expression in PCa and correlates with macrophage infiltration and polarization. Specifically, it drives M1 macrophages polarization while suppressing M2 macrophages polarization via the miR-148a-3p/ARRDC3 axis, thereby impeding tumor immune evasion and restricting PCa progression.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555779","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

Dysregulation of G6PD by HPV E6 exacerbates cervical cancer by activating the STAT3/PLOD2 pathway. HPV E6对G6PD的失调通过激活STAT3/PLOD2通路加重宫颈癌。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf005

Jie Zhang, Wei Dong, Qin Yang, Li-Na Liu, Xi-Lun Cai, Dan Wang, Guo-Ji Yan, Yan-Bin Xiyang, Tao Hu, Jie Zhang

{"title":"Dysregulation of G6PD by HPV E6 exacerbates cervical cancer by activating the STAT3/PLOD2 pathway.","authors":"Jie Zhang, Wei Dong, Qin Yang, Li-Na Liu, Xi-Lun Cai, Dan Wang, Guo-Ji Yan, Yan-Bin Xiyang, Tao Hu, Jie Zhang","doi":"10.1093/carcin/bgaf005","DOIUrl":"10.1093/carcin/bgaf005","url":null,"abstract":"High-risk human papillomavirus (HPV) infection is strongly linked to the initiation and progression of cervical cancer (CC), yet the precise molecular mechanisms involved remain partially understood. This investigation examined differential protein expression profiles in various cohorts, including healthy controls and HPV-positive CC patients with different expression levels of glucose-6-phosphate dehydrogenase (G6PD), shedding light on the dysregulation of oncogenic proteins by HPV. Proteomic analysis of cervical tissues revealed specific protein signatures, indicating significant upregulation of HPV E6, G6PD, STAT3, phosphorylated STAT3, and procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in HPV-infected CC tissues and cell lines. Functional experiments, involving the manipulation of G6PD and STAT3 activities in CC cells with HPV E6 modulation, demonstrated that dysregulated G6PD enhanced cell proliferation, migration, and invasion while suppressing apoptosis, primarily through the STAT3/PLOD2 pathway. Integrating these findings with the existing literature underscores the role of G6PD as an oncogene, potentially under STAT3 regulation, and highlights the role of PLOD2 as a pivotal factor in CC progression. This study also proposed a mechanism in which HPV E6-induced dysregulation of G6PD activates the STAT3-PLOD2 axis to promote CC progression. Understanding the intricate interplay between HPV E6, G6PD, STAT3, and PLOD2 offers valuable insights into the molecular landscape of CC. These findings may pave the way for targeted therapeutic approaches aimed at disrupting this axis to mitigate the progression of CC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405741","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

Genetic determinants and clinical significance of circulating and tumor-specific levels of insulin-like growth factor binding protein 7 (IGFBP7) in a Swedish breast cancer cohort. 瑞典乳腺癌队列中胰岛素样生长因子结合蛋白7 （IGFBP7）循环和肿瘤特异性水平的遗传决定因素和临床意义

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf020

Christopher Godina, Ann H Rosendahl, Kelin Gonçalves de Oliveira, Somayeh Khazaei, Sofie Björner, Karin Jirström, Karolin Isaksson, Michael N Pollak, Helena Jernström

{"title":"Genetic determinants and clinical significance of circulating and tumor-specific levels of insulin-like growth factor binding protein 7 (IGFBP7) in a Swedish breast cancer cohort.","authors":"Christopher Godina, Ann H Rosendahl, Kelin Gonçalves de Oliveira, Somayeh Khazaei, Sofie Björner, Karin Jirström, Karolin Isaksson, Michael N Pollak, Helena Jernström","doi":"10.1093/carcin/bgaf020","DOIUrl":"https://doi.org/10.1093/carcin/bgaf020","url":null,"abstract":"Previous research indicates that insulin-like growth factor binding protein 7 (IGFBP7) protein levels in breast cancer tissue and blood are prognostic. However, genetic determinants of IGFBP7 in breast cancer remain largely unexplored. We examined IGFBP7 in a cohort of 1701 patients with first breast cancer from Sweden, enrolled prior to surgery 2002-16 and followed for up to 15 years. Genotyping was performed on blood samples using OncoArray. Tumor-specific protein levels of IGFBP7, insulin receptor (InsR), and IGF-I receptor (IGFIR) were assessed on tumor tissue microarrays in 964 patients. Furthermore, 275 patients had plasma IGFBP7 levels measured. A genetic proxy marker for circulating IGFBP7 levels was constructed from five candidate single-nucleotide polymorphisms (SNPs) (rs6852762, rs1714014, rs9992658, rs10004910, and rs4865180) based on number of recessive genotypes. Age-adjusted linear regression was used to evaluate SNPs and tumor-specific IGFBP7 levels in relation to circulating IGFBP7 levels. Cox regression adjusted for age, tumor characteristics, and adjuvant treatments was used to assess associations with clinical outcomes. Circulating and tumor-specific IGFBP7 levels were significantly positively correlated. High circulating and genetically predicted IGFBP7 levels were associated with increased risk for distant metastasis and all-cause mortality. A significant interaction between high tumor-specific IGFBP7 levels and membrane-bound InsR resulted in a four-fold increased risk of breast cancer events and distant metastases. Both measured and genetically predicted IGFBP7 levels were independent prognostic biomarkers in breast cancer.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"46 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983694","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