Identification and validation of the clinical prediction model and biomarkers based on chromatin regulators in colon cancer by integrated analysis of bulk- and single-cell RNA sequencing data

Yichao Ma ^1,2, Fang Fang ², Kai Liao ³

⁰Clinical Medical College, Yangzhou University, Yangzhou, China.

Translational Cancer Research +

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April 15, 2024

View abstract on PubMed

Summary

This study identifies key chromatin regulators (CRs) for colon adenocarcinoma (COAD) and develops a prognostic model. The gene PKM is highlighted as critical for cancer prognosis and potentially linked to drug sensitivity.

Area Of Science

Oncology
Genomics
Molecular Biology

Background

Chromatin regulators (CRs) are crucial in cancer development.
Their specific roles in colon adenocarcinoma (COAD) require comprehensive investigation.

Purpose Of The Study

To identify CRs for clinical diagnosis and treatment recommendations in COAD.
To elucidate the mechanisms underlying their critical roles in COAD.

Main Methods

Utilized TCGA and GEO databases for data acquisition.
Employed Weighted Gene Co-Expression Network Analysis (WGCNA) and LASSO-Cox regression for CR screening and model construction.
Integrated single-cell, immune infiltration, mutation, methylation, and drug sensitivity analyses.
Validated gene expression via qRT-PCR and performed pan-cancer analysis.

Main Results

Identified 32 tumor-associated CRs and developed a prognostic model using 8 key CRs (RCOR2, PPARGC1A, PKM, RAC3, PHF19, MYBBP1A, ORC1, EYA2).
The model demonstrated an immune-related association, with lower risk scores correlating with increased immune infiltration and better response.
PKM emerged as a critical gene, implicated in mutations, methylation, drug sensitivity, and prognosis across multiple cancers.

Conclusions

A novel prognostic model for COAD based on CRs was developed.
The core gene PKM's elevated expression is associated with poor prognosis in various cancers, suggesting its significance in COAD progression and treatment.

Keywords:

Chromatin regulators (CRs) colon cancer immunity treatment tumor microenvironment