Identification and Validation of Mitophagy-Related Biomarkers in Colorectal Cancer: An Integrated Analysis of Single-Cell Transcriptome and Mendelian Randomization.

IF 1.9 4区生物学 Q4 GENETICS & HEREDITY

Genetics research Pub Date : 2026-01-01 DOI:10.1155/genr/5579542

Jingyi Zhao, Meng Kong, Sining Wang, Zhixin Cao, Xiangguo Tian

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引用次数: 0

Abstract

Mitophagy is essential for cancer formation and invasion, but its role in colorectal cancer (CRC) remains unclear. We obtained sequencing data and mitophagy-related genes (MP-RGs) from public databases. Differential expression analysis and weighted gene coexpression network analysis (WGCNA) identified mitophagy-related differentially expressed genes (DE-MPGs). Mendelian randomization (MR) analysis identified candidate genes with genetically supported causal relevance to CRC. Biomarkers were identified using machine learning, receiver operating characteristic (ROC) analysis and expression studies. Single-cell RNA sequencing (scRNA-seq) analyzed biomarker expression profiles in various CRC cell types. Quantitative PCR (qPCR) validated biomarker expression in clinical CRC samples. 147 DE-MPGs were identified. MR analysis revealed seven genes with potential causal contributions to CRC susceptibility. Three genes, SGCE (IVW: OR = 1.00041, p = 0.011), ATP8B2 (IVW: OR = 0.99920, p = 0.042), and RANGAP1 (IVW: OR = 0.99861, p = 0.002), were selected as biomarkers. Immune microenvironment and checkpoint differences were observed between CRC and controls. Biomarker expression varied among cell types. qPCR showed decreased SGCE and ATP8B2 and increased RANGAP1 in CRC. SGCE, ATP8B2, and RANGAP1 can serve as mitophagy-related biomarkers with genetically supported causal relevance to CRC, providing new insights for CRC diagnosis and therapy.

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结直肠癌中线粒体自噬相关生物标志物的鉴定和验证：单细胞转录组和孟德尔随机化的综合分析。

线粒体自噬对癌症的形成和侵袭至关重要，但其在结直肠癌（CRC）中的作用尚不清楚。我们从公共数据库中获得测序数据和有丝分裂相关基因（MP-RGs）。差异表达分析和加权基因共表达网络分析（WGCNA）鉴定了有丝分裂相关的差异表达基因（DE-MPGs）。孟德尔随机化（MR）分析确定了与结直肠癌具有遗传支持因果关系的候选基因。使用机器学习、受试者工作特征（ROC）分析和表达研究识别生物标志物。单细胞RNA测序（scRNA-seq）分析了各种结直肠癌细胞类型的生物标志物表达谱。定量PCR （qPCR）验证了临床结直肠癌样本中生物标志物的表达。共鉴定出147个de - mpg。MR分析揭示了7个与结直肠癌易感性有潜在因果关系的基因。选择SGCE （IVW: OR = 1.00041, p = 0.011）、ATP8B2 （IVW: OR = 0.99920, p = 0.042）和RANGAP1 (IVW: OR = 0.99861, p = 0.002) 3个基因作为生物标志物。免疫微环境和检查点在结直肠癌和对照组之间存在差异。不同细胞类型的生物标志物表达不同。qPCR结果显示CRC中SGCE和ATP8B2降低，RANGAP1升高。SGCE、ATP8B2和RANGAP1可以作为与CRC有丝分裂相关的生物标志物，具有遗传支持的因果关系，为CRC的诊断和治疗提供新的见解。

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来源期刊

Genetics research 生物-遗传学

自引率

6.70%

发文量

审稿时长

>12 weeks

期刊介绍： Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.