Identification of two novel biomarkers of rectal carcinoma progression and prognosis via co-expression network analysis

mRNA expression profiles provide important insights on a diversity of biological processes involved in rectal carcinoma (RC). Our aim was to comprehensively map complex interactions between the mRNA expression patterns and the clinical traits of RC. We employed the integrated analysis of five microarray datasets and The Cancer Genome Atlas rectal adenocarcinoma database to identify 2118 consensual differentially expressed genes (DEGs) in RC and adjacent normal tissue samples, and then applied weighted gene co-expression network analysis to parse DEGs and eight clinical traits in 66 eligible RC samples. A total of 16 co-expressed gene modules were identified. The green-yellow and salmon modules were most appropriate to the pathological stage (R = 0.36) and the overall survival (HR = 13.534, P = 0.014), respectively. A diagnostic model of the five pathological stage hub genes (SCG3, SYP, CDK5R2, AP3B2, and RUNDC3A) provided a powerful classification accuracy between localized RC and non-localized RC. We also found increased Secretogranin III (SCG3) expression with higher pathological stage and poorer prognosis in the test and validation set. The increased Homer scaffolding protein 2 (HOMER2) expression with the favorable survival prediction efficiency significantly correlated with the markedly reduced overall survival of RC patients and the higher pathological stage during the test and validation set. Our findings indicate that the SCG3 and HOMER2 mRNA levels should be further evaluated as predictors of pathological stage and survival in patients with RC.