Decoding Colon Cancer Heterogeneity Through Integrated miRNA–Gene Network Analysis

Qingcai He, Zhilong Mi (), Tianyue Liu, Taihang Huang, Mao Li, Binghui Guo () and Zhiming Zheng
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Qingcai He: School of Mathematical Sciences, Beihang University, Beijing 100191, China
Zhilong Mi: LMIB and SKLCCSE, Beihang University, Beijing 100191, China
Tianyue Liu: LMIB and SKLCCSE, Beihang University, Beijing 100191, China
Taihang Huang: School of Mathematical Sciences, Beihang University, Beijing 100191, China
Mao Li: LMIB and SKLCCSE, Beihang University, Beijing 100191, China
Binghui Guo: LMIB and SKLCCSE, Beihang University, Beijing 100191, China
Zhiming Zheng: LMIB and SKLCCSE, Beihang University, Beijing 100191, China

Mathematics, 2025, vol. 13, issue 6, 1-21

Abstract: Colon adenocarcinoma (COAD) demonstrates significant clinical heterogeneity across disease stages, gender, and age groups, posing challenges for unified therapeutic strategies. This study establishes a multi-dimensional stratification framework through integrative analysis of miRNA–gene co-expression networks, employing the MRNETB algorithm coupled with Markov flow entropy (MFE) centrality quantification. Analysis of TCGA-COAD cohorts revealed stage-dependent regulatory patterns centered on CDX2-hsa-miR-22-3p-MUC13 interactions, with progressive dysregulation mirroring tumor progression. Gender-specific molecular landscapes have emerged, characterized by predominant SLC26A3 expression in males and GPA33 enrichment in females, suggesting divergent pathogenic mechanisms between genders. Striking age-related disparities were observed, where early-onset cases exhibited molecular signatures distinct from conventional COAD, highlighted by marked XIST expression variations. Drug-target network analysis identified actionable candidates including CEACAM5-directed therapies and differentiation-modulating agents. Our findings underscore the critical need for heterogeneity-aware clinical decision-making, providing a roadmap for stratified intervention paradigms in precision oncology.

Keywords: COAD; mutual information; miRNA; Markov Flow Entropy; co-expression network; clinical stratification (search for similar items in EconPapers)
JEL-codes: C (search for similar items in EconPapers)
Date: 2025
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