Screening of Serum miRNAs Combination Biomarkers for Colorectal Cancer and Analysis on Multi-tumor Spectrum Expansion
DUAN Mingjun
MU Lan
WU Zhuo
Abstract：Objective To systematically screen differentially expressed microRNAs(miRNAs)in serum of colorectal cancer patients based on high-throughput sequencing technology,construct a multi-miRNA combination diagnostic biomarker,and provide novel molecular markers for early non-invasive diagnosis of colorectal cancer.Methods A case-control study design was adopted,including 30 patients with colorectal cancer and 20 healthy controls.High-throughput small RNA sequencing was performed using the Illumina HiSeq 2500 platform to screen for differentially expressed miRNAs(log2 Fold Change,|log2FC|≥1,P＜0.05).Target genes were predicted using miRanda and RNAhybrid algorithms,and Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted using the DAVID platform.Receiver operating characteristic(ROC)curve analysis and logistic regression methods were employed to construct the optimal miRNA combination diagnostic model.Results High-throughput sequencing identified a total of 205 differentially expressed miRNAs,including 98 upregulated and 107 downregulated.Functional enrichment analysis revealed that differential miRNAs were mainly enriched in tumor-related biological processes such as Notch signaling pathway(P＜0.01),autophagy-related pathways(P＜0.05),and transmembrane receptor protein tyrosine kinase signaling pathway(P＜0.001).A 5-miRNA combination diagnostic biomarker consisting of miR-21-5p,miR-92a-3p,miR-155-5p,miR-143-3p,and miR-145-5p was successfully constructed,with an area under the ROC curve of 0.924(95%CI:0.867-0.981),diagnostic sensitivity of 90.00%,and specificity of 85.00%,significantly superior to traditional serum tumor markers CEA(AUC=0.663)and CA19-9(AUC=0.598).This biomarker also demonstrated excellent diagnostic efficacy for early-stage colorectal cancer(stage Ⅰ-Ⅱ)(AUC=0.895).Conclusion The 5-miRNA serum combination biomarker screened based on high-throughput sequencing has excellent diagnostic efficacy for colorectal cancer,especially suitable for early non-invasive screening,providing a new molecular tool for the precise diagnosis and clinical decision-making of colorectal cancer.
Keywords：colorectal cancermicroRNAserumhigh-throughput sequencing
Publication Date：2026-02-28
Online Publishing Date：2026-03-20(First online date of this platform, not the publication date of the document)
Pages：9( 66-74 )