ArticleDiscover oncology2026
Identification of pyroptosis and hypoxia related molecular subtypes and a prognostic signature in colorectal cancer.
Article in Discover oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundColorectal cancer (CRC) is one of the most common malignancies of the gastrointestinal tract and remains a leading cause of cancer-related mortality. Hypoxia and pyroptosis are closely linked to malignant progression and may shape tumour biology and the immune microenvironment.
methodsPyroptosis- and hypoxia-related genes were obtained from GeneCards and MSigDB, and PHRGs were defined as the intersection of pyroptosis- and hypoxia-associated gene sets for subsequent consensus clustering. Transcriptomic profiles and survival information for CRC were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Pyroptosis- and hypoxia-related molecular subtypes were identified using consensus clustering. Least absolute shrinkage and selection operator and Cox regression analyses were applied to construct a prognostic signature. Key signature genes were preliminarily assessed at the expression level in paired CRC and adjacent normal tissues using qRT-PCR (n = 10 pairs) and western blotting (n = 6 pairs). Given the limited sample size and lack of stage- or subtype-stratified validation, these experiments provide preliminary expression-level support rather than functional confirmation.
resultsPatients were classified into four PHRG-related molecular subtypes with distinct prognoses and biological characteristics, with PHRGcluster C2 showing the worst outcome. A total of 1578 pyroptosis- and hypoxia-related differentially expressed genes (PHRDEGs) were identified across the four PHRGclusters. A six-gene prognostic signature (PHRDEGscore) was then established in the TCGA cohort. Patients with a high PHRDEGscore had shorter survival, which was validated in external cohorts (GSE39582 and GSE17536). The low-PHRDEGscore group exhibited higher immune infiltration (e.g., activated CD8+ and CD4+ T cells), and an exploratory association with immunotherapy response was observed in a non-CRC immunotherapy-treated cohort (IMvigor210). Experimental analyses indicated higher mRNA levels of HES4, SHROOM2, and OXCT1 in CRC tissues than in adjacent normal tissues (qRT-PCR, n = 10 pairs), and increased protein expression of HES4 and SHROOM2 (western blotting, n = 6 pairs).
conclusionsThis study identified hypoxia- and pyroptosis-related molecular patterns and a six-gene prognostic signature in CRC. The observed associations are correlative and hypothesis-generating. Prospective validation in independent, well-annotated clinical cohorts is needed before any clinical application can be considered.
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