An integrative analysis of transcriptome, methylome and single-cell RNA sequencing data identifies UBE2H as a marker of oxaliplatin resistance in colorectal cancer

作者：Jinman Fang, Qizhi Zhu, Bo Hong, Xueling Li, Hongzhi Wang · 发表于：Cancer Cell International · 年份：2025 · DOI：10.1186/s12935-025-03996-4 · 被引用次数：4 · 研究领域：Colorectal Cancer Treatments and Studies、Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis

Metastatic colorectal cancer is commonly treated with oxaliplatin. However, patients may develop resistance to treatment over time, and currently, there are no validated predictive biomarkers for this resistance. A differential analysis of the transcriptome and DNA methylome of colorectal cancer cell lines, classified by their varying IC50 values for oxaliplatin, revealed that genes associated with resistance were enriched for interferon regulatory factor pathways. In contrast, sensitive genes showed enrichment for transcription, amino acid metabolism, development, and binding motifs of c-MyC:Max, AP1 and others. In univariate Cox’s proportional hazard model analysis, it was found that UBE2H expression is linked to shorter survival time in the TCGA dataset and was further validated across five GEO datasets of colorectal cancer. The transcription of UBE2H, along with its gene body methylation, and copy number variation was found to be higher in resistant cell lines compared to sensitive ones. Additionally, UBE2H levels were higher in cancer samples than in control samples, while the promoter methylation is lower in cancer samples than in control samples. In groups with high UBE2H, there was an increased infiltration of eight cell types, including CD8 + T cells and type 2 T helper cells. Conversely, only T helper 17 cells showed reduced infiltration. Moreover, UBE2H expression was positively correlated with checkpoint inhibitors, CTLA4 and PDCD1, along with immune regulatory ge...