Work

A predefined sulphur-handling transcriptional programme is associated with colorectal cancer molecular subtypes

Year: 2026

Type: article

Abstract: Background Colorectal cancer (CRC) exhibits substantial metabolic and transcriptomic heterogeneity, but the relationship between sulphur-handling transcriptional programmes and consensus molecular subtypes (CMS) remains incompletely resolved. Methods We analysed a predefined 14-gene sulphur-handling panel across The Cancer Genome Atlas colon and rectal adenocarcinoma cohorts (TCGA-COAD/READ) and six independent HG-U133 validation cohorts ( n = 1,337 tumours). Analytical workflows integrated differential expression comparing tumours with adjacent-normal mucosa, CMS association modelling, random-effects meta-analysis, adjustment for three orthogonal tumour-purity estimators (ESTIMATE, consensus purity estimates, and ABSOLUTE), reference-based single-cell deconvolution with independent cross-atlas verification, and direction-aware therapeutic triage. Results Colorectal tumours demonstrated branch-specific transcriptional alterations, marked by coordinated downregulation of sulphur oxidation and clearance genes ( SQOR , ETHE1 , TST ) and of the cysteine-catabolism genes CDO1 and CTH , and selective upregulation of SLC7A11 and AHCY , whereas CBS was not significantly altered. The composite programme score differed across CMS subtypes and was consistently lower in mesenchymal CMS4 tumours than in non-CMS4 tumours across all discovery and validation series. This association remained statistically detectable after adjustment for three global tumour-purity metrics. The programme score showed no statistically detectable independent association with overall, recurrence-free, or disease-free survival. Single-cell deconvolution supported expression across epithelial, stromal, and immune compartments. Direction-aware therapeutic triage prioritised SLC7A11/xCT inhibition as an exploratory candidate for preclinical testing. Conclusion Sulphur-handling transcriptional architecture is reproducibly linked to CRC molecular taxonomy and is not fully explained by measured tumour purity variation, providing a computational framework for future functional and compartment-resolved investigation of sulphur metabolism in stratified CRC populations.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1976885

Authors: Shaheryar Shafi, Arslan Hamid, Jiao Yang, Xiaoxia Cheng, Minxuan Sun

Institutions: University of Science and Technology of China, Chinese Academy of Sciences, Suzhou Institute of Biomedical Engineering and Technology, University Hospital Bonn, Nanjing University

Language: English

Topic: Colorectal Cancer Treatments and Studies

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801