Identification and clinical validation of metastasis-associated biomarkers based on large-scale samples in colon-adenocarcinoma

Abstract

Aim: Distant metastasis is the main cause of death in patients with colon-adenocarcinoma(COAD). Due to the lack of effective molecular markers and treatment, the prognosis of patients with metastatic colon cancer is still rather poor.

Methods: Metastatic related signature (MRS) of stage I and stage IV in colon cancer were identified from different cohorts. Univariate cox regression is used to analyze the relationship between MRS and the overall survival. L1000FWD and DGIdb databases are used to identify molecular drugs. Expression and functional experimental validation of the hub MRS were carried out.

Results: 16 MRS were identified, of which 14 MRS was significantly correlated with overall survival. Further functional enrichment analysis showed that MRS was significantly involved with important biological functions such as cell migration, and apoptosis. As important metastatic related genes, GSR, FAS and CYP1B1 have significant interaction with drug molecules. Further studies have confirmed that the expression of FAS and GSR is low, and inhibition of its expression can promote the metastasis of COAD. CYP1B1 expression is highly expressed, and inhibition of its expression can attenuate the malignant biological behavior of colon cancer.

Conclusion: Our research could increase the understanding of the mechanism of colon cancer metastasis and provide theoretical basis for the treatment of metastatic colon cancer.

Keywords: Biological behavior; COAD; CYP1B1; FAS; GSR; Metastatic related signatures; Prognostic biomarker.