Development and validation of a metabolic gene signature for predicting overall survival in patients with colon cancer
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ORIGINAL ARTICLE
Development and validation of a metabolic gene signature for predicting overall survival in patients with colon cancer Jun Ren1 · Juan Feng2 · Wei Song1 · Chuntao Wang1 · Yuhang Ge1 · Tao Fu1 Received: 16 March 2020 / Accepted: 1 August 2020 © Springer Nature Switzerland AG 2020
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. Keywords Colon cancer · Metabolism · Risk signature · Prognosis
Introduction Colorectal cancer (CRC) is one of the most common intestinal malignancies worldwide. It has the third highest incidence among cancers and remains the second most common cause of cancer mortality [1]. Due to new understanding of genetic factors in cancer, the introduction of screening tests, and the improvement of treatment, the morbidity and mortality of CRC have declined [2]. However, CRC is a highly Jun Ren and Juan Feng contributed equally to this work. * Tao Fu [email protected] 1
Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, No. 238, Jiefang Road, Wuhan 430060, Hubei, China
Department of Breast Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China
2
heterogeneous disease [3]. The postoperative survival rates of CRC patients with different stages vary widely. For example, the 5-year survival rate for patients with stage IV CRC is 90%
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