Comprehensive analysis of HOXC8 associated with tumor microenvironment characteristics in colorectal cancer.

BACKGROUND

Accumulating evidence have highlighted the essential roles of HOX genes in embryonic development and carcinogenesis. As a member of the HOX gene family, the abnormal expression of gene is associated with the progression and metastasis of various tumors. However, potential roles of HOXC8 in colorectal cancer (CRC) prognosis and tumor microenvironment (TME) remodeling remain unclear.

METHODS

We conducted an integrated analysis of clinical and molecular characteristics, relevant oncogenic and immune regulation roles and drug sensitivity features of HOXC8 in CRC.

RESULTS

expression was markedly high expressed in CRC samples compared to normal samples, and the upregulated expression of was associated with poor prognosis. High expression was significantly associated with invasion-related pathways especially epithelial-mesenchymal transition (EMT). In vitro experiments showed significantly up-regulated expression in some CRC cell lines and its promoting effect on EMT and cell proliferation. TME categorization through transcriptomic analysis of CRC patients with high expression identified two different TME subtypes known as immune-enriched with fibrotic subtype and immune-depleted subtype. Patients with immune-enriched, fibrotic subtype exhibited significantly longer progression-free survival (PFS), upregulated PD-L1 and CTLA4 expression and higher TMB than those with the immune-depleted subtype.

CONCLUSIONS

overexpression was associated with poor prognosis and specific TME subtypes in CRC. This study provided valuable resource for further exploring the potential mechanisms and therapeutic targets of HOX genes in CRC.