CALB2 Expression Is Associated with Tumor Progression and Prognosis in Colorectal Adenocarcinoma

Background: Globally, colorectal adenocarcinoma (COAD) continues to be one of the most frequent contributors to cancer-associated deaths, pointing out an ongoing demand for robust biomarkers capable of reflecting disease advancement and predicting patient outcomes. Calbindin 2 (CALB2), a calcium-binding protein, has been implicated in tumor progression in several malignancies, but the precise functional involvement of this molecule in COAD remains insufficiently characterized. This study aimed to examine the clinical relevance and functional significance of CALB2 in COAD. Methods: Clinical tissue-based analyses, bioinformatic analyses of publicly available datasets, in vitro and in vivo functional assays, and targeted metabolomic profiling were performed to evaluate CALB2 in COAD. Results: Immunofluorescence analysis of a COAD tissue microarray revealed that CALB2 expression was more frequently detected in stage III tumors and was associated with the proliferation marker Ki67. The Cancer Genome Atlas (TCGA) cohort’s bioinformatic analyses revealed an increase in CALB2 expression with advancing pathological T stage, and it was associated with poorer overall survival. Functional experiments demonstrated that CALB2 expression accelerated tumor growth in vivo and promoted the migration and proliferation of colorectal adenocarcinoma cells in vitro. At the molecular level, altered CALB2 expression was associated with changes in epithelial–mesenchymal transition-related markers, p53 Ser33 phosphorylation, and amino acid-related metabolic profiles. Conclusions: Collectively, these findings show a correlation between CALB2 expression and poor clinical outcomes and disease progression in colorectal adenocarcinoma.