Development and validation of a metabolic gene signature for predicting overall survival in patients with colon cancer

Abstract

The reprogramming of cellular metabolism is a hallmark of tumorigenesis. However, the prognostic value of metabolismrelated genes in colon cancer remains unclear. This study aimed to identify a metabolic gene signature to categorize colon cancer patients into high-and low-risk groups and predict prognosis. Samples from the Gene Expression Omnibus database were used as the training cohort, while samples from The Cancer Genome Atlas database were used as the validation cohort. A metabolic gene signature was established to investigate a robust risk stratification for colon cancer. Subsequently, a prognostic nomogram was established combining the metabolism-related risk score and clinicopathological characteristics of patients. A total of 351 differentially expressed metabolism-related genes were identified in colon cancer. After univariate analysis and least absolute shrinkage and selection operator-penalized regression analysis, an eight-gene metabolic signature (MTR, NANS, HADH, IMPA2, AGPAT1, GGT5, CYP2J2, and ASL) was identified to classify patients into high-and low-risk groups. High-risk patients had significantly shorter overall survival than low-risk patients in both the training and validation cohorts. A high-risk score was positively correlated with proximal colon cancer (P = 0.012), BRAF mutation (P = 0.049), and advanced stage (P = 0.027). We established a prognostic nomogram based on metabolism-related gene risk score and clinicopathologic factors. The areas under the curve and calibration curves indicated that the established nomogram showed a good accuracy of prediction. We have established a novel metabolic gene signature that could predict overall survival in colon cancer patients and serve as a biomarker for colon cancer.

Expression Status and Prognostic Significance of Gamma-Glutamyl Transpeptidase Family Genes in Hepatocellular Carcinoma

“…Wei and coworkers (12) discovered that GGT5 was highly expressed in cancer-associated fibroblasts in lung cancer, predicting the poor survival of patients with lung cancer. GGT5 was also regarded as the key metabolism-related gene in gastric cancer (28) and colon cancer (29). In our study, we found an association between high expression of GGT5 mRNA and relatively favorable progression-free survival rather than OS.…”

Construction of a Lactate-Related Prognostic Signature for Predicting Prognosis, Tumor Microenvironment, and Immune Response in Kidney Renal Clear Cell Carcinoma

“…Recently, growing evidence has demonstrated its significant role in different carcinomas. For example, several studies have demonstrated that the overexpression of HADH was related to poor clinical outcomes in acute myeloid leukemia and colon cancer (55,56). Additionally, Shen et al illustrated that the downregulation of HADH facilitated gastric cancer cell migration and invasion through activating the Akt signaling pathway, associated with more advanced stage and poorer outcomes (57).…”

“…Recently, growing evidence has demonstrated its significant role in different carcinomas. For example, several studies have demonstrated that the overexpression of HADH was related to poor clinical outcomes in acute myeloid leukemia and colon cancer ( 55 , 56 ). Additionally, Shen et al.…”

Lipid Metabolism in Cancer: The Role of Acylglycerolphosphate Acyltransferases (AGPATs)

“…In colorectal carcinoma (CRC), expression analysis of lipid metabolism genes of patient tumor samples [ 82 ], as well as transcriptomic meta-analysis studies of CRC patient data [ 83 , 84 ], showed that the increased expression of AGPAT1 is associated with a high risk of relapse and shorter survival. Accordingly, AGPAT1 has been identified as a negative prognostic marker of CRC and was included in metabolic gene signatures that could help to classify CRC patients and be used for the development of precision therapies [ 82 , 83 , 84 ].…”