Identification of prognostic gene markers for the early diagnosis of colorectal cancer

Abstract Background: Colorectal Cancer (CRC) is the frequently occurring malignant tumor in colon and rectum with high mortality rate. The signaling pathway involved in CRC and CRC driven genes are largely unknown. Methods To identify the gene signatures which help in early diagnosis of CRC, we downloaded three datasets (GSE24514, GSE8671 and GSE21510) from the Gene Expression Omnibus (GEO) Database. GO and KEGG pathway enrichment analysis were conducted using DAVID database. A protein–protein interaction (PPI) network was constructed using STRING and cytoscape software. These hub genes were verified by survival analysis using GEPIA database. Results A total of 120 DEGs were identified including (75 upregulated genes and 45 downregulated genes). Seven modules were identified from protein –protein interaction network using MCODE plug in tool of cytoscape, only three Modules (1, 2 and 3) selected with score ≥ 5 and node ≥ 10. Module 1 contained downregulated genes and Module 2 and 3 contained upregulated genes. Hub genes identified from Module 1 with connectivity score ≥ 16 included CDK1, CCNB1, FOXM1, RRM2, MAD2L1, NEK2, MCM4 and PBK. Out of 8 genes examined, only 3 exhibited significant correlations with overall survival among CRC patients (p > 0.05). MAD2L1, MCM4, and PBK demonstrated relatively lower expression levels of these genes were correlated with poor prognosis in CRC patients. Hub genes from Modules 2 and 3 (connectivity score ≥ 6) included MYL9, CNN1, MYH11, MYLK, TAGLN, GUCA2A, GUCA2B, ZG16 and SLC26A3. Survival analysis indicated that higher expression of MYL9, CNN1 and TAGLN correlated with poor prognosis, while lower expression of ZG16 and SLC26A3 was linked to poorer outcomes in CRC patients (p MAD2L1, MCM4, PBK, MYL9, CNN1, TAGLN, ZG16 and SLC26A3) were identified, to be strongly correlated with the overall survival of patients with CRC based on GEO and GEPIA data. These eight genes have the potential as novel and independent prognostic biomarkers for early diagnosis of CRC and forecasting clinical results of CRC patients. Several studies revealed that suppression of these genes inhibits the proliferation of CRC.