Upregulation ofHOXA10Protein Expression Predicts Poor Prognosis for Colorectal Cancer

Abstract

The homeobox (HOX) genes function as transcriptional factors that can promote tumorigenesis. However, the expression profile of HOXA10 and the role this protein plays in solid tumors are unclear. Here we examined HOXA10 protein expression in samples from colorectal cancer (CRC) patients to address the clinical significance of this protein. Seven independent investigations from the Oncomine database were retrieved. A total of 85 patients who underwent radical excision followed by 5-fluorouracil (5-FU)-based adjuvant chemotherapy were enrolled. Immunohistochemistry was performed on pairs of cancerous and normal tissues to detect the expression of both HOXA10, and the phosphatase and tensin homolog deleted on chromosome ten (PTEN). Lentivirus-mediated RNA interference was used to knock down HOXA10 expression in LoVo and HT-29 cell lines, then cells' proliferation, apoptosis, and tumor growth in vivo were detected. Oncomine data showed that HOXA10 expression was significantly upregulated in CRC tissues compared with relevant normal controls. In our study, 58 cases (68.2%) showed positive HOXA10 protein expression in tumor tissue and negative expression in normal tissues. HOXA10 protein upregulation was consistent with PTEN downregulation. Although not related to clinicopathological parameters, a significant correlation was found between HOXA10 upregulation and a decreased 5-year disease-free survival (DFS). A Cox proportional hazards model further suggested that HOXA10 overexpression was an independent factor to predict DFS of CRC patients. Furthermore, HOXA10 knockdown significantly increased sensitivity to 5-FU chemotherapy in vitro and in vivo. Significant HOXA10 overexpression in CRC may be a potential biomarker indicating poor prognosis and 5-FU resistance.