Identification and validation of a prognostic risk-scoring model based on sphingolipid metabolism-associated cluster in colon adenocarcinoma.

Abstract

Colon adenocarcinoma (COAD) is the primary factor responsible for cancer-related mortalities in western countries, and its development and progression are affected by altered sphingolipid metabolism. The current study aimed at investigating the effects of sphingolipid metabolism-related (SLP) genes on multiple human cancers, especially on COAD. We obtained 1287 SLP genes from the GeneCard and MsigDb databases along with the public transcriptome data and the related clinical information. The univariate Cox regression analysis suggested that 26 SLP genes were substantially related to the prognosis of COAD, and a majority of SLP genes served as the risk genes for the tumor, insinuating a potential pathogenic effect of SLP in COAD development. Pan-cancer characterization of SLP genes summarized their expression traits, mutation traits, and methylation levels. Subsequently, we focused on the thorough research of COAD. With the help of unsupervised clustering, 1008 COAD patients were successfully divided into two distinct subtypes (C1 and C2). C1 subtype is characterized by a poor prognosis, activation of SLP pathways, high expression of SLP genes, disordered carcinogenic pathways, and immune microenvironment. Based on the clusters of SLP, we developed and validated a novel prognostic model, consisting of ANO1, C2CD4A, EEF1A2, GRP, HEYL, IGF1, LAMA2, LSAMP, RBP1, and TCEAL2, to quantitatively evaluate the clinical outcomes of COAD. The Kaplain-Meier survival curves and ROC curves highlighted the accuracy of our SLP model in both internal and external cohorts. Compared to normal colon tissues, expression of C2CD4A was detected to be significantly higher in COAD; whereas, expression levels of EEF1A2, IGF1, and TCEAL2 were detected to be significantly lower in COAD. Overall, our research emphasized the pathogenic role of SLP in COAD and found that targeting SLP might help improve the clinical outcomes of COAD. The risk model based on SLP metabolism provided a new horizon for prognosis assessment and customized patient intervention.