Abstract
In this study, we collected genes related to energy metabolism, used gene expression data from public databases to classify molecular subtypes of colon cancer (COAD) based on the genes related to energy metabolism, and further evaluated the relationships between the molecular subtypes and prognosis and clinical characteristics. Differential expression analysis of the molecular subtypes yielded 1948 differentially expressed genes (DEGs), whose functions were closely related to the occurrence and development of cancer. Based on the DEGs, we constructed a 4-gene prognostic risk model and identified the high expression of FOXD4, ENPEP, HOXC6, and ALOX15B as a risk factor associated with a high risk of developing COAD. The 4-gene signature has strong robustness and a stable predictive performance in datasets from different platforms not only in patients with early COAD but also in all patients with colon cancer. The enriched pathways of the 4-gene signature in the high- and low-risk groups obtained by GSEA were significantly related to the occurrence and development of colon cancer. Moreover, the results of qPCR, immunohistochemistry staining and Western blot assay revealed that FOXD4, ENPEP, HOXC6, and ALOX15B are over expressed in CRC tissues and cells. These results suggesting that the signature could potentially be used as a prognostic marker for clinical diagnosis.
Highlights
Colon cancer is the fourth most common cancer worldwide and the third leading cause of cancer death [1]
Energy metabolism is the basis of tumor cell proliferation and invasion
Energy metabolism is the basis of tumor cell proliferation and invasion, and most tumor cells show deviation from the normal energy metabolism state so that they can survive and eventually grow under challenging microenvironmental conditions [16]
Summary
Colon cancer is the fourth most common cancer worldwide and the third leading cause of cancer death [1]. In 2018, it was estimated that 97,220 new cases of colon cancer would be diagnosed. It is estimated that 50,630 people would die from colon and rectal cancers [2]. The rates of colon cancer have been falling: the incidence per 100,000 population decreased from 60.5 in 1976 to 46.4 in 2005 and to 40.7 from 2009 to 2013 [3, 4]. From 1990 to 2007, colon cancer mortality decreased by nearly 35% [5]. The annual death rate and number of deaths from colon cancer remain high, and research on colon cancer and the development of treatment strategies for colon cancer remain important
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