Crosstalk Between Immunity and Oncogenes Within the Tumor Microenvironment of HPV-Associated Cervical Squamous Cell Carcinoma.

IF 2.8 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

OncoTargets and therapy Pub Date : 2025-08-15 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S537872

Reham M Alahmadi, Halah Z Al Rawi, Maaweya Awadalla, Bashayer Saeed, Basma Abdelazeem, Huda M Alshanbari, Bandar Alosaimi

{"title":"Crosstalk Between Immunity and Oncogenes Within the Tumor Microenvironment of HPV-Associated Cervical Squamous Cell Carcinoma.","authors":"Reham M Alahmadi, Halah Z Al Rawi, Maaweya Awadalla, Bashayer Saeed, Basma Abdelazeem, Huda M Alshanbari, Bandar Alosaimi","doi":"10.2147/OTT.S537872","DOIUrl":null,"url":null,"abstract":"Introduction: Every two minutes, a woman dies from cervical cancer, which is considered the fourth most common cancer among women worldwide. The dynamic interplay between tumor inflammation, immune crosstalk, oncogenes, and tumor suppressor genes plays a crucial role in tumor development and progression.Methods: Using clinical and integrated bioinformatics, the mRNA expression pattern of 168 immune and tumor-related genes in the tumor microenvironment (TME) of HPV-positive cervical squamous cell carcinoma (CSCC) was analyzed.Results: The study identified 94 DEGs, of which 55 genes were remarkably upregulated, including CASP8, ZHX2, BCL2L1, CTNNB1, RB1, BAX, CD274, CCL20, FOXP3, and CCL18. The top three-fold changes were associated with CASP8, ZHX2, and BCL2L1, respectively. In contrast, downregulation was discovered for 39 genes associated with immunity, regulation of cell cycle, and DNA damage response (HRAS, CCND1, ATM, CXCR1, and MIF). Gene-gene interaction and correlation analysis showed positive correlations, including RB1 and CASP8, RB1 and BCL2L1, and CCL20 with CCL18. Notably, six genes exhibited increased expression and showed a strong correlation with enhanced overall survival (OS) and disease-free survival (DFS), indicating their potential utility as prognostic biomarkers. Upregulated genes were positively associated with various immune cells, including B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells. Functional enrichment analysis revealed involvement in cancer-related processes, inflammatory responses, and cell migration, with key pathways linked to cytokine signaling and chemokine receptor interactions.Discussion: Through the integration of clinical, experimental, and computational analyses, potential therapeutic targets and prognostic biomarkers were identified that may help improve clinical outcomes. Future studies should focus on the functional assays of identified genes both in vitro and in vivo.","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"899-920"},"PeriodicalIF":2.8000,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363556/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"OncoTargets and therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/OTT.S537872","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: Every two minutes, a woman dies from cervical cancer, which is considered the fourth most common cancer among women worldwide. The dynamic interplay between tumor inflammation, immune crosstalk, oncogenes, and tumor suppressor genes plays a crucial role in tumor development and progression.

Methods: Using clinical and integrated bioinformatics, the mRNA expression pattern of 168 immune and tumor-related genes in the tumor microenvironment (TME) of HPV-positive cervical squamous cell carcinoma (CSCC) was analyzed.

Results: The study identified 94 DEGs, of which 55 genes were remarkably upregulated, including CASP8, ZHX2, BCL2L1, CTNNB1, RB1, BAX, CD274, CCL20, FOXP3, and CCL18. The top three-fold changes were associated with CASP8, ZHX2, and BCL2L1, respectively. In contrast, downregulation was discovered for 39 genes associated with immunity, regulation of cell cycle, and DNA damage response (HRAS, CCND1, ATM, CXCR1, and MIF). Gene-gene interaction and correlation analysis showed positive correlations, including RB1 and CASP8, RB1 and BCL2L1, and CCL20 with CCL18. Notably, six genes exhibited increased expression and showed a strong correlation with enhanced overall survival (OS) and disease-free survival (DFS), indicating their potential utility as prognostic biomarkers. Upregulated genes were positively associated with various immune cells, including B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells. Functional enrichment analysis revealed involvement in cancer-related processes, inflammatory responses, and cell migration, with key pathways linked to cytokine signaling and chemokine receptor interactions.

Discussion: Through the integration of clinical, experimental, and computational analyses, potential therapeutic targets and prognostic biomarkers were identified that may help improve clinical outcomes. Future studies should focus on the functional assays of identified genes both in vitro and in vivo.

查看原文本刊更多论文

hpv相关宫颈鳞状细胞癌肿瘤微环境中免疫与癌基因间的串扰

引言：每两分钟就有一名妇女死于宫颈癌，宫颈癌被认为是全球第四大女性常见癌症。肿瘤炎症、免疫串扰、癌基因和肿瘤抑制基因之间的动态相互作用在肿瘤的发生和发展中起着至关重要的作用。方法：应用临床和综合生物信息学方法，分析hpv阳性宫颈鳞状细胞癌（CSCC）肿瘤微环境（TME）中168个免疫及肿瘤相关基因的mRNA表达谱。结果：共鉴定出94个DEGs，其中55个基因显著上调，包括CASP8、ZHX2、BCL2L1、CTNNB1、RB1、BAX、CD274、CCL20、FOXP3和CCL18。前三倍的变化分别与CASP8、ZHX2和BCL2L1相关。相比之下，与免疫、细胞周期调节和DNA损伤反应相关的39个基因（HRAS、CCND1、ATM、CXCR1和MIF）被发现下调。基因-基因互作及相关分析显示，RB1与CASP8、RB1与BCL2L1、CCL20与CCL18呈正相关。值得注意的是，6个基因表达增加，并与总生存期（OS）和无病生存期（DFS）增强密切相关，表明它们作为预后生物标志物的潜在效用。上调的基因与多种免疫细胞呈正相关，包括B细胞、CD8+和CD4+ T细胞、巨噬细胞、中性粒细胞和树突状细胞。功能富集分析显示参与癌症相关过程，炎症反应和细胞迁移，与细胞因子信号传导和趋化因子受体相互作用相关的关键途径。讨论：通过整合临床、实验和计算分析，确定了可能有助于改善临床结果的潜在治疗靶点和预后生物标志物。未来的研究应集中在体外和体内鉴定基因的功能分析上。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.