Identification and validation of a novel six-gene signature based on mucinous adenocarcinoma-related gene molecular typing in colorectal cancer

Abstract

Background and objectives Colorectal mucinous adenocarcinoma (MAC) is a particular pathological type that has yet to be thoroughly studied. This study aims to investigate the characteristics of colorectal MAC-related genes in colorectal cancer (CRC), explore the role of MAC-related genes in accurately classifying CRC, and further construct a prognostic signature. Methods CRC samples were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). MAC-related differentially expressed genes (DEGs) were analyzed in TCGA samples. Based on colorectal MAC-related genes, TCGA CRC samples were molecularly typed by the non-negative matrix factorization (NMF). According to the molecular subtype characteristics, the RiskScore signature was constructed through univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Clinical significance in CRC of the RiskScore signature was analyzed. A nomogram was further built based on the RiskScore signature. Results From the colorectal MAC-related genes, three distinct molecular subtypes were identified. A RiskScore signature composed of six CRC subtype-related genes (CALB1, MMP1, HOXC6, ZIC2, SFTA2, and HYAL1) was constructed. Patients with high-RiskScores had the worse prognoses. RiskScores led to differences in gene mutation characteristics, antitumor drug sensitivity, and tumor microenvironment of CRC. A nomogram based on the signature was developed to predict the one-, three-, and five-year survival of CRC patients. Conclusion MAC-related genes were able to classify CRC. A RiskScore signature based on the colorectal MAC-related molecular subtype was constructed, which had important clinical significance for guiding the accurate stratification of CRC patients.