Site- and assay-specific prognostic and treatment-response evidence for HEPACAM2 in colorectal cancer: a systematic scoping review

HEPACAM2 participates in mitotic regulation and centrosome maturation, but its biomarker relevance may differ by tumor site, assay, tissue timing, and treatment context. We separately mapped transcriptomic evidence from predominantly untreated colorectal cancer (CRC) datasets and the single protein-level immunohistochemistry (IHC) study in neoadjuvant-treated rectal cancer. PubMed, Embase, Scopus, Web of Science, and CNKI were searched from inception to 6 August 2026. Eligible peer-reviewed studies reported extractable HEPACAM2-specific findings in human CRC or CRC-derived datasets. Evidence was synthesized by directness, assay modality, cancer setting, clinical domain, and translational relevance. Nine studies were included: two HEPACAM2-focused studies, two expression/progression or single-cell studies, and five multigene or molecular-signature studies. Eight were predominantly transcriptomic or bioinformatic; one assessed HEPACAM2 protein by IHC in 343 pretreatment rectal cancer biopsies. In untreated CRC/colon transcriptomic settings, lower HEPACAM2 mRNA was generally associated with progression and adverse prognostic features. One HEPACAM2-focused study reported a TCGA-derived tumor-versus-normal discrimination AUC of 0.931 and better overall survival with higher expression (HR, 0.61; 95% CI, 0.43–0.87; p = 0.007). These estimates were not independently validated; qRT-PCR confirmation of differential expression involved six paired samples. In the single rectal cancer IHC cohort, high pretreatment expression was associated with poor tumor regression and inferior disease-specific, locoregional recurrence-free, and metastasis-free survival. Current evidence comprises distinct site- and assay-specific signals that are not directly comparable. HEPACAM2 remains an exploratory candidate biomarker requiring independent validation using standardized assays, paired RNA–protein assessment, and prespecified clinical endpoints.