Colorectal cancer (CRC) is one of the major cancer types associated with increased mortality worldwide. Hence, identifying reliable biomarkers make it very essential for early diagnosis and prognosis of CRC. Numerous studies have been conducted to decipher molecular mechanisms underlying CRC, however more deep insightful knowledge is the need of the hour. The purpose of this study was to identify promising key candidate genes in colorectal cancer (CRC) and assess their expression and clinical significance. To clarify and verify promising key biomarkers with signal transduction pathways in colorectal cancer, we integrated 11 microarray datasets from NCBI-GEO. This study utilized multiple bioinformatics tools and databases, including OncoDB, GEO2R, UALCAN, GEIPA, TIMER, and DAVID. The gene expression profiles of eleven datasets (GSE10714, GSE113513, GSE13471, GSE15960, GSE24514, GSE32323, GSE41258, GSE4183, GSE44076, GSE44861, GSE9348) were screened. In 11 gene expression profiles, 3 downregulated genes were identified and validated by databases such as OncoDB, UALCAN, GEIPA and TIMER. Downregulation of SLC4A4 with significant predictive value was validated by multi-omic data analysis and validated by Gene Expression Omnibus (GEO). GEIPA survival analysis showed that low SLC4A4 expression correlated with poorer overall survival among CRC patients. Based on this study, we identified SLC4A4 as a potential candidate biomarker for colorectal cancer (CRC), enabling early diagnosis and prognosis with molecular targeted therapy.