GUCA2A Dysregulation as a Promising Biomarker for Accurate Diagnosis and Prognosis of Colorectal Cancer

Abstract

Abstract Background:Colorectal cancer (CRC) is a leading cause of global mortality and presents a significant barrier to improving life expectancy. The primary objective of this study was to discern a unique differentially expressed gene (DEG) that exhibits a strong association with colorectal cancer. By achieving this goal, the research aims to contribute valuable insights to the field of translational medicine. Methods:We performed an analysis on four colorectal cancer microarray datasets obtained from the GEO database in order to identify differentially expressed genes (DEGs). In addition, we explored the TCGA colon adenoma carcinoma (COAD) dataset using GEPIA2, which provided high-throughput RNA-Seq data to identify DEGs associated with COAD. To further investigate, we conducted a comprehensive analysis using a pan-cancer model encompassing 33 different cancer types to identify common DEGs between the GEO datasets and the GEPIA2 COAD-TCGA data. We also performed gene set enrichment analysis using Enrichr to gain insights into the functional relevance of these DEGs. To uncover potential regulatory relationships, we constructed a co-expression network utilizing data from the STRING and LinkedOmics databases. Furthermore, we established a competing endogenous RNA (ceRNA) network by integrating information from the miRTarBase and circBank databases. Additionally, correlation between tumor-immune signatures in distinct tumor microenvironments was investigated using the TISIDB database. Finally, we investigated potential interactions between the identified gene and various drugs, providing valuable insights into therapeutic possibilities. Results:GUCA2A emerged as a significant DEG specific to colorectal cancer (|log2FC| > 1 and adjusted q-value < 0.05). Importantly, GUCA2A exhibited excellent diagnostic performance for COAD, with 98% sensitivity, 95% specificity, and a 99.6% area under the curve (AUC). Moreover, low expression of GUCA2A significantly impacted overall patient survival. Enrichment analysis highlighted the receptor guanylyl cyclase signaling pathway and guanylate cyclase activator activity as the most significant gene ontology terms. A ceRNA network consisting of 8 miRNAs targeting GUCA2A and 183 circRNAs acting as miRNA sponges was constructed. Significant correlations were observed between tumor-immune signatures and GUCA2A expression. Additionally, lactose anhydrous, Atropin, and Volanesorsen sodium were identified as drugs potentially interacting with GUCA2A. Conclusions:This study identifies GUCA2A as a promising prognostic and diagnostic biomarker for colorectal cancer. Further investigations are warranted to explore the potential of GUCA2A as a therapeutic biomarker.