Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025;32(40):9172-9193.
doi: 10.2174/0109298673335900240920070746.

Development of a Mitochondrial Membrane Permeability Transition Prognosis System in Colon Adenocarcinoma: Risk Stratification and Therapeutic Target Identification

Bomiao Zhang  1 , Mingyu Xia  1 , Shihui Zhao  1 , Yien Li  1 , Chenfeng Yu  1 , Liqiang Song  1 , Shaoke Wang  1 , Binbin Cui  1
Affiliations

Development of a Mitochondrial Membrane Permeability Transition Prognosis System in Colon Adenocarcinoma: Risk Stratification and Therapeutic Target Identification

Bomiao Zhang et al. Curr Med Chem. 2025.

Abstract

Aims: Explore the role of mitochondrial membrane permeability transition (MPT) in colon adenocarcinoma (COAD).

Background: Further exploration of risk stratification for COAD prognostic assessment has important clinical value. MPT-related pathways play a key role in the pathogenesis of many human diseases, including tumorigenesis. Its impact on COAD is still unknown.

Objective: Bioinformatics analysis was conducted by analyzing the GEO database and TCGA database, and the bioinformatics results were verified by in vitro experiments.

Methods: Through the analysis of the transcriptome data of 1008 COAD samples in the GEO database and TCGA database, the differential expressions of MPT-related genes in COAD were explored, followed by molecular subtype analysis based on MPT characteristics by univariate Cox algorithm analysis and the consensus clustering algorithm. The gene signature associated with MPT molecular subtypes was further identified and the MPT scoring system was established by the LASSO-univariate Cox analysis algorithm. After evaluating the prognostic value of the MPT scoring system in COAD patients via nomogram establishment, the clinical value of the MPT scoring system was comprehensively analyzed through somatic mutation characteristics analysis, immunotherapy response analysis, immunoinfiltration analysis, and drug sensitivity analysis. CCK-8, WB, PCR, colony formation method, and Transwell method were used to verify the effect of the screened target on the proliferation and invasion of COAD cells.

Results: We successfully established a scoring system related to MPT and validated the prognostic value of COAD patients. The potential clinical value of the MPT scoring system was also analyzed. VSIG4 was selected for further in vitro experiments to verify the effect of the screened targets on the proliferation and invasion ability of COAD cells.

Conclusion: We established an MPT scoring system for effective risk stratification of COAD patients, demonstrating the impact of MPT on the development of COAD and its potential value as an intervention factor.

Keywords: Mitochondrial membrane permeability transition; VSIG4; colon adenocarcinoma; immune infiltration; prognosis.; risk stratification.

PubMed Disclaimer

References

    1. Siegel R.L.; Miller K.D.; Fuchs H.E.; Jemal A.; Cancer statistics, 2022. CA Cancer J Clin 2022,72(1),7-33 - DOI - PubMed
    1. Eng C.; Yoshino T.; Ruíz-García E.; Mostafa N.; Cann C.G.; O’Brian B.; Benny A.; Perez R.O.; Cremolini C.; Colorectal cancer. Lancet 2024,404(10449),294-310 - DOI - PubMed
    1. Patel S.G.; Dominitz J.A.; Screening for colorectal cancer. Ann Intern Med 2024,177(4),ITC49-ITC64 - DOI - PubMed
    1. Brandi G.; Ricci A.D.; Rizzo A.; Zanfi C.; Tavolari S.; Palloni A.; De Lorenzo S.; Ravaioli M.; Cescon M.; Is post-transplant chemotherapy feasible in liver transplantation for colorectal cancer liver metastases? Cancer Commun 2020,40(9),461-464 - DOI - PubMed
    1. Rizzo A.; Nannini M.; Novelli M.; Dalia Ricci A.; Scioscio V.D.; Pantaleo M.A.; Dose reduction and discontinuation of standard-dose regorafenib associated with adverse drug events in cancer patients: a systematic review and meta-analysis. Ther Adv Med Oncol 2020,12 - DOI - PubMed

MeSH terms

LinkOut - more resources