Anti-oncogenic and immunological functions of ATP23 in CMS4 colon adenocarcinoma based on a machine learning
Yafei Yin1, Huimin Zhang1, Shuai Li1
1Department of Gastroenterology, The Second Qilu Hospital of Shandong University, Jinan, China.
Background:
Consensus Molecular Subtype (CMS) 4 and BRAF mutations are poor prognostic indicators for colon adenocarcinoma (COAD). Although the prevalence of BRAF-mutated COAD is higher in the CMS1 subtype, we have identified certain cases of CMS4 subtypes in patients with BRAF mutations. However, there is currently a lack of research exploring whether this particular type of COAD exhibits a worse prognosis and unraveling its underlying mechanism.
Methods:
This retrospective study analyzed the transcriptome profiles and clinical parameters of COAD patients from six public datasets. Kaplan-Meier plots and bioinformatics methods predicted the correlation between ATP23 expression and patient survival. We compared enriched pathways, genomic mutations, immune cell infiltration, copy number alterations, cell-cell communication, and TIDE scores between ATP23-high and ATP23-low groups. Furthermore, in vitro experiments verified the potential roles of ATP23 in COAD.
Results:
The expression of ATP23 was significantly lower in tumor tissues, particularly in the CMS4 subtype. No significant correlation was observed between ATP23 expression and clinical characteristics or molecular mutations in COAD. Higher ATP23 levels were associated with improved survival rates in COAD patients. In vitro experiments indicated that ATP23 inhibits the proliferation, migration, and invasion capabilities of COAD cells. Moreover, decreased ATP23 expression may impair oxidative phosphorylation in T cells, contributing to the formation of an immune-evasive microenvironment, and potentially leading to reduced efficacy of both immunotherapy and conventional chemotherapy.
Conclusions:
ATP23 is a potential prognostic marker for COAD patients. Reduced ATP23 expression may inhibit oxidative phosphorylation in T cells and contribute to the formation of an immunosuppressive microenvironment.
Insights
ATP23 is a potential prognostic marker for colon adenocarcinoma (COAD). Lower ATP23 expression correlates with poor prognosis and immune evasion, impacting treatment efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Consensus Molecular Subtype (CMS) 4 and BRAF mutations are poor prognostic indicators in colon adenocarcinoma (COAD).
- While BRAF mutations are common in CMS1, they are also found in CMS4 COAD, a subtype lacking extensive mechanistic and prognostic research.
- Investigating the prognostic significance and underlying mechanisms of BRAF-mutated CMS4 COAD is crucial.
Purpose of the Study:
- To investigate the prognostic value of ATP23 expression in colon adenocarcinoma (COAD).
- To explore the correlation between ATP23 expression and Consensus Molecular Subtype (CMS) 4 and BRAF mutations in COAD.
- To elucidate the potential mechanisms by which ATP23 influences COAD progression and the tumor microenvironment.
Main Methods:
- Retrospective analysis of transcriptome profiles and clinical data from six public COAD datasets.
- Kaplan-Meier survival analysis and bioinformatics to assess ATP23 expression's correlation with patient survival.
- In vitro experiments to validate ATP23's role in COAD cell behavior and immune cell function.
Main Results:
- ATP23 expression was significantly lower in COAD tumor tissues, especially in the CMS4 subtype.
- Higher ATP23 levels were associated with improved patient survival and inhibited COAD cell proliferation, migration, and invasion.
- Reduced ATP23 expression may impair T cell oxidative phosphorylation, fostering an immune-evasive microenvironment and potentially reducing treatment efficacy.
Conclusions:
- ATP23 serves as a potential prognostic biomarker for colon adenocarcinoma (COAD).
- Decreased ATP23 expression is linked to an immunosuppressive tumor microenvironment and poorer outcomes.
- Targeting ATP23 may offer therapeutic strategies for COAD patients, particularly those with CMS4 subtype.
