Carcinogenesis最新文献

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

A novel tRNA-derived small RNA 5'-tiRNA-His is a promising biomarker for diagnosis of colorectal cancer. 一种新的trna衍生的小RNA 5'-tiRNA-His是一种很有希望用于结直肠癌诊断的生物标志物。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-05-22 DOI: 10.1093/carcin/bgaf026

Xinliang Gu, Xincheng Yang, Danping Zhu, Xinwei Liu, Junjie Nie, Tao Xu, Yuqin Pan, Huiling Sun, Shukui Wang

{"title":"A novel tRNA-derived small RNA 5'-tiRNA-His is a promising biomarker for diagnosis of colorectal cancer.","authors":"Xinliang Gu, Xincheng Yang, Danping Zhu, Xinwei Liu, Junjie Nie, Tao Xu, Yuqin Pan, Huiling Sun, Shukui Wang","doi":"10.1093/carcin/bgaf026","DOIUrl":"https://doi.org/10.1093/carcin/bgaf026","url":null,"abstract":"Colorectal cancer (CRC) is one of the most serious gastrointestinal tumors. The survival rate of patients with advanced stages is meager, so it is urgent to identify new diagnostic biomarkers with high sensitivity and specificity. tRNA-derived small RNAs (tsRNAs) are an emerging class of small non-coding RNAs that are highly abundant in the blood of cancer patients and are associated with various physiological and pathological processes. Therefore, the clinical value of tsRNAs in diagnosing CRC requires further investigation. In this study, we identified the differential expression profiles of tsRNAs in CRC tissues via Pandora sequencing. We selected 5'-tiRNA-His that were significantly highly expressed in CRC plasma and tissues for further investigation. Interestingly, the expression level of 5'-tiRNA-His was increased dramatically in the plasma of CRC patients and correlated with various clinicopathologic parameters. ROC analysis revealed that 5'-tiRNA-His had good diagnostic value in diagnosing CRC patients, superior to that of CEA, CA199, and CA724, and could significantly differentiate patients with CRC from healthy donors and patients with intestinal polyps. Moreover, 5'-tiRNA-His still had good diagnostic efficacy in the diagnosis of patients with early-stage CRC, and the diagnostic efficacy was further elevated when combined with clinically used tumor markers. In conclusion, our study identified plasma 5'-tiRNA-His as a promising biomarker for diagnosing and screening CRC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118926","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

Current Challenges and Potential Opportunities for Interception and Prevention of Head and Neck Cancer. 当前的挑战和潜在的机会拦截和预防头颈癌。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-05-18 DOI: 10.1093/carcin/bgaf025

Karam El-Bayoumy, Neil Christensen, James Broach, Craig Meyers, Douglas Stairs, Mitchell Machtay, Jiafen Hu, Zachary T Bitzer, Todd D Schell, Kun-Ming Chen, Yuan-Wan Sun, Dhimant Desai, Vonn Walter, Junjia Zhu

{"title":"Current Challenges and Potential Opportunities for Interception and Prevention of Head and Neck Cancer.","authors":"Karam El-Bayoumy, Neil Christensen, James Broach, Craig Meyers, Douglas Stairs, Mitchell Machtay, Jiafen Hu, Zachary T Bitzer, Todd D Schell, Kun-Ming Chen, Yuan-Wan Sun, Dhimant Desai, Vonn Walter, Junjia Zhu","doi":"10.1093/carcin/bgaf025","DOIUrl":"https://doi.org/10.1093/carcin/bgaf025","url":null,"abstract":"Globally, the incidence of head and neck squamous cell carcinoma (HNSCC) has increased over recent decades and is projected to continue to rise, largely driven by increases in oropharyngeal squamous cell carcinoma (OPSCC) which is linked to HPV infection. HPV infection is also involved in the development of other cancers (anogenital and cervical) and almost 100% of cervical cancer patients are positive for HPV. OPSCC is the most common HPV-associated cancer in men and has exceeded the incidence of cervical cancer cases in women in the US. Our knowledge of the carcinogenesis process from HPV infection to OPSCC development has been primarily extrapolated from cervical cancer models. While the cooperation of tobacco smoking and HPV infection is documented in cervical cancer, mechanistic studies to address this interaction in management and control of HNSCC are scarce and are also extrapolated from cervical cancer models. The molecular heterogeneity of HNSCC constitutes a tremendous challenge, and despite advances in several fronts in the management and control of HSNCC, short- and long-term treatment-associated morbidities remain substantial. In addition to deaths directly caused by this disease, survivors of this cancer have the second highest rate of suicide compared with other cancers survivors. Given the existing gaps in our knowledge and the current clinical challenges, future studies including a number of new conceptual and methodological elements discussed in this review can lead to the discovery of biomarkers for early detection of the disease and novel strategies which will advance our knowledge to intercept and prevent HNSCC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092900","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

Delta 4-desaturase sphingolipid 2 enhances prostate cancer stem-like traits through phytoceramide-mediated PI3K-AKT signaling pathway. 德尔塔4-去饱和酶鞘脂2通过植物神经酰胺介导的PI3K-AKT信号通路增强前列腺癌茎样性状。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-05-17 DOI: 10.1093/carcin/bgaf024

Yuanyuan Luo, Jiachuan Yu, Qi Li, Xiaolin Wang, Xinyu Liu, Guowang Xu, Wangshu Qin

{"title":"Delta 4-desaturase sphingolipid 2 enhances prostate cancer stem-like traits through phytoceramide-mediated PI3K-AKT signaling pathway.","authors":"Yuanyuan Luo, Jiachuan Yu, Qi Li, Xiaolin Wang, Xinyu Liu, Guowang Xu, Wangshu Qin","doi":"10.1093/carcin/bgaf024","DOIUrl":"https://doi.org/10.1093/carcin/bgaf024","url":null,"abstract":"Cancer stem cells (CSCs) are the initiating cells of tumorigenesis, metastasis, and recurrence and play a crucial role in androgen deprivation therapy resistance, yet how sphingolipid metabolism promotes CSC maintenance remains exclusive. Here, we conducted gene expression profiling of sphere-derived castration-resistant prostate cancer stem cells (PCSCs) and identified enhanced sphingolipid de novo biosynthesis with upregulated DEGS2 expression in PCSCs. Silencing of DEGS2 significantly suppressed prostate cancer stem-like traits, cell growth, clonogenicity, and metastasis, while ectopic overexpression of DEGS2 showed the opposite effects. Mechanistically, DEGS2-synthesized phytoceramide activates PI3K-AKT signaling pathway to promote cancer stem-like characteristics, and activation of AKT reversed DEGS2-depletion-inhibited cancer stem-like properties. Clinically, prostate cancer tissues expressed higher levels of DEGS2 compared with adjacent normal tissue, and DEGS2 expression exhibits strong correlations with SOX2, CD133 and Snail expression in primary prostate carcinomas. Collectively, our data illustrate that DEGS2 dictates prostate cancer stem-like properties via the PI3K-AKT pathway, and disruption of this pathway provides potential therapeutic strategies for prostate cancer.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086063","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

NUF2 and NEK2 promote malignant progression of gallbladder cancer by remodeling the extracellular matrix. NUF2和NEK2通过重塑细胞外基质促进胆囊癌的恶性进展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-12 DOI: 10.1093/carcin/bgaf019

Ming Gao, Peng Ye, Yutong Zhang, Yarong Guo, Jun Xu

{"title":"NUF2 and NEK2 promote malignant progression of gallbladder cancer by remodeling the extracellular matrix.","authors":"Ming Gao, Peng Ye, Yutong Zhang, Yarong Guo, Jun Xu","doi":"10.1093/carcin/bgaf019","DOIUrl":"https://doi.org/10.1093/carcin/bgaf019","url":null,"abstract":"Gallbladder cancer (GBC) ranks as the most common malignant tumor of the biliary tract, which has been characterized by late diagnosis, low excisional rate, and poor prognosis. Recent studies exploring the roles of malignant progression associated genes in GBC remain limited. Our study aims to identify significant hub genes involved in its pathogenesis, which may serve as novel potential therapeutic targets for GBC. Here, we employed RNA-seq analysis to identify differentially expressed genes (DEGs) of 7 GBC samples and 5 matched adjacent samples. After screening the DEGs in clinical sequencing data and GSE139682, we further obtained 549 genes with consistent expression trend in two datasets, including 155 upregulated and 394 downregulated genes. Gene Ontology (GO) enrichment analysis revealed that these genes were significantly enriched in extracellular matrix (ECM) related processes, such as organization, structure, and composition, which hint us that remodeling of ECM may be the main driving factor for the malignant progression of GBC. Additionally, we screened 17 candidate hub genes through protein-protein interaction (PPI) network analysis and Cytoscape, subsequent GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the remodeled ECM mainly functions by affecting cell division. Moreover, we found that NEK2 and NUF2 were overexpressed in GBC tumor tissues and validated their function in pro-proliferation of GBC cell. Our results highlight that NEK2 and NUF2 may be hub genes promoting the malignant progression of GBC and are expected to be reliable new therapeutic targets for GBC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977441","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 variants in glycosylation pathways are associated with colorectal cancer risk. 糖基化途径中的遗传变异与结直肠癌风险相关。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-10 DOI: 10.1093/carcin/bgae075

Huiyu Wang, Hanchi Wu, Xiaoting He, Hao Wang, Junying Xu, Junli Ding, Shuwei Li, Dong Hua, Meilin Wang

{"title":"Genetic variants in glycosylation pathways are associated with colorectal cancer risk.","authors":"Huiyu Wang, Hanchi Wu, Xiaoting He, Hao Wang, Junying Xu, Junli Ding, Shuwei Li, Dong Hua, Meilin Wang","doi":"10.1093/carcin/bgae075","DOIUrl":"https://doi.org/10.1093/carcin/bgae075","url":null,"abstract":"The glycosylation pathway serves as a vital regulatory mechanism in colorectal cancer. However, how genetic variants in these pathways may affect the risk of colorectal cancer is still unknown. To examine the relationships between the risk of colorectal cancer and the presence of selected single-nucleotide polymorphisms (SNPs), 1,150 patients and 1,342 controls were included in this case‒control study. We found that GALNT2 rs76000797 and rs11576324, GALNT6 rs67726586, FUT8 rs117497405, FUT2 rs111311275 and B4GALT5 rs6125695 were strongly correlated with the risk of colorectal cancer. Moreover, rs111311275 exhibited an expression quantitative trait locus effect on FUT2 in colorectal cancer tissues, which could increase the risk of colorectal cancer by influencing FUT2 expression. GEPIA research and microarray data revealed that FUT2 expression was higher in colorectal cancer tissues than in normal tissues and that individuals with colon cancer with high expression of FUT2 had longer overall survival times. Our study highlights the significant impact of genetic variants on glycosylation pathways and offers novel insights into potential biomarkers for colorectal cancer risk.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964243","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

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

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