Identification and Validation of Serum Biomarkers to Improve Colorectal Cancer Diagnosis

The pressing need for reliable biomarkers in colorectal cancer (CRC) diagnosis and prognosis is a major global health concern. Current diagnostic methods rely heavily on invasive procedures like colonoscopy, and existing biomarkers such as Carbohydrate Antigen 19-9 (CA19-9) and Carcinoembryonic Antigen (CEA) exhibit limitations in accuracy and specificity.

This study aims to identify and validate novel biomarkers that can enhance the early detection and diagnostic precision of CRC while overcoming the shortcomings of conventional biomarkers.

Leveraging advancements in genomic and proteomic technologies, gene expression datasets were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We identified differentially expressed genes (DEGs) and conducted further analyses, including Gene Ontology (GO) enrichment and Protein-Protein Interaction (PPI) network construction. Five promising biomarkers-INHBA, MMP7, PSAT1, SLC7A5, and TGFBI-were selected based on their robust performance in Receiver Operating Characteristic (ROC) curve analysis. Serum concentrations of these biomarkers were measured in 200 CRC patients and 100 healthy controls.

The study revealed significantly elevated expression levels of the selected biomarkers in CRC tissues compared to normal tissues. Additionally, serum concentrations of INHBA, MMP7, PSAT1, SLC7A5, and TGFBI were notably higher in CRC patients than in healthy individuals, with Area Under the Curve (AUC) values ranging from 0.8361 to 0.9869 indicating high diagnostic accuracy. Optimal cutoff values for diagnosis ranged from 38.9 pg/mL to 280.7 pg/mL, yielding sensitivity and specificity values between 74.5% and 92.9%.

The findings underscore the potential of INHBA, MMP7, PSAT1, SLC7A5, and TGFBI as effective non-invasive biomarkers for CRC detection. Their elevated serum concentrations and robust discriminatory abilities highlight their promise in improving diagnostic accuracy and patient outcomes compared to traditional biomarkers.

The identification and validation of these novel biomarkers represent a significant advancement in CRC diagnosis and management. Further studies are required to validate their clinical applicability in larger cohorts and to elucidate their functional roles in CRC pathogenesis, ultimately enhancing diagnostic strategies and personalized treatment approaches.