Multi-omic analysis identifies cholesterol metabolism related protein ARV1 as a novel biomarker for Colon adenocarcinoma patients with adenomatous polyposis.

Abstract

Objectives: Familial adenomatous polyposis (FAP) is typically characterized by numerous adenomatous polyps that will inevitably progress to adenocarcinomas. To enhance the clinical management of colon adenocarcinoma (COAD), a deeper understanding of the molecular mechanisms driving malignant transformation in pre-cancerous adenomatous polyposis, as well as the identification of predictive biomarkers, is essential.

Methods: In the present study, clinical samples were collected from rare patients with COAD and FAP, and metabolomic and proteomic analyses were performed to elucidate the mechanisms of canceration in FAP patients.

Results: The multi-omics analysis showed that cholesterol metabolism is highly activated in COAD tissue and identified 64 genes that are highly expressed in COAD and significantly correlated with prognosis. Improved in situ sequencing (IISS) identified ARV1 (ACAT related enzyme 2 required for viability 1) as a critical regulator of cholesterol metabolism. Finally, bioinformatics analysis using the HPA database showed that ARV1 expression is negatively correlated with COAD TNM stage; thus, indicating that ARV1 might play a role as a tumor suppressor in colon cancer.

Conclusions: Overall, cholesterol metabolism was found to be involved in colon adenocarcinoma tumorigenesis and ARV1 was identified as a key factor in the early stage of FAP transformation.