Development of a Novel Prognostic Panel for Colorectal Cancer Based on Cancer Functional Status, and Validation of STC2 as a Promising Biomarker.

ABSTRACT

BACKGROUND: Improving the clinical outcome of colorectal cancer (CRC) patients remains a major challenge. This study aimed to develop a new predictive classifier for CRC and to examine its relationship with the immune environment and therapeutic response. METHODS: A comprehensive bioinformatics analysis was applied to develop a risk panel comprised of cancer function status-related genes (CFSRGs). This panel was evaluated for prognostic utility by Area Under the Curve (AUC) and Kaplan-Meier (KM) analyses. Differences between high- and low-risk groups were subsequently investigated using multi-omics data. Immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (qRT-PCR), and cell phenotype assays were also employed to ascertain the clinical value of STC2 expression. RESULTS: Significant differences were observed in the survival rate between high- and low-risk groups defined by our 7-CFSRG panel, both in internal and external CRC patient cohorts. The AUC for prediction of survival at 1-, 3- and 5-years was satisfactory in all cohorts. Detailed analysis revealed that tumor mutation burden, drug sensitivity, and pathological stage were closely associated with the risk score. Elevated expression of STC2 in CRC tissues relative to normal paraneoplastic tissues was associated with less favorable patient outcomes. qRT-PCR experiments confirmed that STC2 expression was significantly upregulated in several CRC cell lines (HCT116, SW480, and LOVO) compared to a normal intestinal epithelial cell line (NCM460). The proliferation, migration, and invasion of CRC cells were all significantly inhibited by knockdown of STC2. CONCLUSIONS: Our 7-CFSRG panel is a promising classifier for assessing the prognosis of CRC patients. Moreover, the targeting of STC2 may provide a novel therapeutic approach for improving patient outcomes.