CPLX1 is a novel prognostic biomarker in CRC correlating with immunotherapy resistance and ferroptosis.

IF 5.7 2区医学 Q1 IMMUNOLOGY

Frontiers in Immunology Pub Date : 2025-07-09 eCollection Date: 2025-01-01 DOI:10.3389/fimmu.2025.1589423

Canyu Liu, Qiujun Liu, Yuanhao Lv, Tingmin Chang, Shiyi Song, Yuang Ding, Jiateng Zhong, Yanxuan Liu

{"title":"CPLX1 is a novel prognostic biomarker in CRC correlating with immunotherapy resistance and ferroptosis.","authors":"Canyu Liu, Qiujun Liu, Yuanhao Lv, Tingmin Chang, Shiyi Song, Yuang Ding, Jiateng Zhong, Yanxuan Liu","doi":"10.3389/fimmu.2025.1589423","DOIUrl":null,"url":null,"abstract":"Background: Colorectal cancer (CRC) remains a predominant contributor to cancer-related mortality globally, with its resistance to immunotherapeutic strategies presenting a formidable challenge in patient management. Recent investigations have illuminated the prospective involvement of ferroptosis, a regulated form of cell death, in both cancer progression and the development of resistance to therapeutic interventions.Objective: This study aims to elucidate the prognostic significance of CPLX1 in CRC, specifically its correlation with immunotherapy resistance and its association with ferroptosis, thereby contributing to a deeper understanding of tumor biology and therapeutic vulnerability.Methods: We conducted an integrative analysis of RNA-seq datasets from the TCGA-COAD and TCGA-READ projects, along with the GEO GSE156451 dataset, to discern differentially expressed genes. Expression levels of CPLX1 were evaluated utilizing the TIMER 2.0 database, and survival analyses were performed via Kaplan-Meier plots and Cox regression modeling to assess prognostic implications. Additionally, mutational analyses through cBioPortal and COSMIC datasets were employed to identify CPLX1 mutations in COAD. Co-expression and functional enrichment analyses, alongside Gene Set Enrichment Analysis (GSEA), were also conducted to delineate pathways impacted by CPLX1.Results: Our findings indicate that high expression levels of CPLX1 are significantly correlated with poor prognostic outcomes in CRC patients. Through immune infiltration analyses employing ssGSEA, we observed notable associations between CPLX1 expression and specific immune cell populations. Furthermore, the interaction between CPLX1 and ferroptosis-related genes suggests a potential mechanistic linkage that could underpin therapeutic resistance.Conclusion: CPLX1 is identified as a novel prognostic biomarker in CRC, exhibiting clear correlations with both immunotherapy resistance and ferroptosis. These findings indicate that targeting CPLX1 may provide novel therapeutic strategies to ameliorate treatment resistance in CRC.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1589423"},"PeriodicalIF":5.7000,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283636/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fimmu.2025.1589423","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Colorectal cancer (CRC) remains a predominant contributor to cancer-related mortality globally, with its resistance to immunotherapeutic strategies presenting a formidable challenge in patient management. Recent investigations have illuminated the prospective involvement of ferroptosis, a regulated form of cell death, in both cancer progression and the development of resistance to therapeutic interventions.

Objective: This study aims to elucidate the prognostic significance of CPLX1 in CRC, specifically its correlation with immunotherapy resistance and its association with ferroptosis, thereby contributing to a deeper understanding of tumor biology and therapeutic vulnerability.

Methods: We conducted an integrative analysis of RNA-seq datasets from the TCGA-COAD and TCGA-READ projects, along with the GEO GSE156451 dataset, to discern differentially expressed genes. Expression levels of CPLX1 were evaluated utilizing the TIMER 2.0 database, and survival analyses were performed via Kaplan-Meier plots and Cox regression modeling to assess prognostic implications. Additionally, mutational analyses through cBioPortal and COSMIC datasets were employed to identify CPLX1 mutations in COAD. Co-expression and functional enrichment analyses, alongside Gene Set Enrichment Analysis (GSEA), were also conducted to delineate pathways impacted by CPLX1.

Results: Our findings indicate that high expression levels of CPLX1 are significantly correlated with poor prognostic outcomes in CRC patients. Through immune infiltration analyses employing ssGSEA, we observed notable associations between CPLX1 expression and specific immune cell populations. Furthermore, the interaction between CPLX1 and ferroptosis-related genes suggests a potential mechanistic linkage that could underpin therapeutic resistance.

Conclusion: CPLX1 is identified as a novel prognostic biomarker in CRC, exhibiting clear correlations with both immunotherapy resistance and ferroptosis. These findings indicate that targeting CPLX1 may provide novel therapeutic strategies to ameliorate treatment resistance in CRC.

查看原文本刊更多论文

CPLX1是一种新的CRC预后生物标志物，与免疫治疗耐药性和铁凋亡相关。

背景：结直肠癌（CRC）仍然是全球癌症相关死亡的主要原因，其对免疫治疗策略的耐药性对患者管理提出了巨大挑战。最近的研究已经阐明了铁下垂（一种受调节的细胞死亡形式）在癌症进展和对治疗干预的抗性发展中的潜在参与。目的：本研究旨在阐明CPLX1在结直肠癌中的预后意义，特别是其与免疫治疗耐药的相关性以及与铁上落的相关性，从而有助于更深入地了解肿瘤生物学和治疗易感性。方法：我们对TCGA-COAD和TCGA-READ项目的RNA-seq数据集以及GEO GSE156451数据集进行了综合分析，以识别差异表达基因。利用TIMER 2.0数据库评估CPLX1的表达水平，并通过Kaplan-Meier图和Cox回归模型进行生存分析，以评估预后影响。此外，通过cbiopportal和COSMIC数据集进行突变分析以确定COAD中的CPLX1突变。共表达和功能富集分析以及基因集富集分析（GSEA）也被用于描述受CPLX1影响的通路。结果：我们的研究结果表明，CPLX1的高表达水平与CRC患者的不良预后显著相关。通过使用ssGSEA进行免疫浸润分析，我们观察到CPLX1表达与特定免疫细胞群之间存在显著关联。此外，CPLX1和嗜铁相关基因之间的相互作用提示了一种潜在的机制联系，可能支持治疗耐药性。结论：CPLX1被认为是一种新的CRC预后生物标志物，与免疫治疗耐药和铁上吊均有明显的相关性。这些发现表明，靶向CPLX1可能为改善结直肠癌的治疗耐药提供新的治疗策略。

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

Frontiers in Immunology IMMUNOLOGY-

CiteScore

9.80

自引率

11.00%

发文量

7153

审稿时长

14 weeks

期刊介绍： Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.