HOXA13 overexpression is associated with poor prognosis in colorectal liver metastases^☆

Curative-intent hepatectomy in colorectal cancer liver metastasis (CRCLM) is guided by clinical criteria; however, molecular biomarkers may enhance prognostication. Homeobox (HOX) gene family is often dysregulated in cancer and may serve as a prognostic tool in metastatic colorectal cancer. Bulk RNA extraction was performed in frozen colorectal liver tumors (N = 39), and differentially expressed HOX genes using clinical risk scores were studied using supervised hierarchical clustering. In sum, 667 differentially expressed genes were found (p < 0.05), including multiple HOXA and HOXD family genes (p < 0.01; q < 0.01). Three long non-coding RNA species (lncRNAs) were differentially expressed: HOTTIP, HOXA-AS5, and HOXD-AS2 (p < 0.01; q < 0.01). HOXA13 and HOTTIP were more likely to be expressed in patients with metastatic recurrence (log-rank p = 0.004). A composite HOX score was found to be predictive of OS and RFS (log-rank p = 0.0269 and 0.0273, respectively). HOXA13, HOXD4, and HOXD8 were explored in five independent cohorts. HOX genes and their associated lncRNAs exhibit prognostic associations in patients with CRCLM and may act as biomarkers to refine clinical decision-making.