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Background  Chemoresistance often develops in esophageal squamous cell carcinoma (ESCC), leading to poor prognosis.  HOX  genes play a crucial role in embryonic development and cell differentiation. Studies have recently linked  HOX  with chemoresistance, thus we explored whether  HOXA13  is involved in ESCC chemoresistance.    Methods  One hundred thirty‐one ESCC patients who received neoadjuvant chemotherapy were enrolled.  HOXA13  expression was examined by immunohistochemistry. RNA interference was used to knock down the  HOXA13  expression in KYSE70 and transfected HOXA13 plasmid to overexpress  HOXA13  in KYSE510 cells. We examined half‐maximal inhibitory concentration of cisplatin, apoptosis, and epithelial‐to‐mesenchymal transition (EMT) in ESCC cell lines with different  HOXA13  expression levels by cell counting kit‐8, flow cytometry, and transwell analysis.    Results  The median survival of patients with high  HOXA13  expression was significantly shorter than those with low expression ( P  = 0.027).  HOXA13  was associated with worse tumor regression grade ( P  = 0.009). Low  HOXA13  expressed cells decreased the half‐maximal inhibitory concentration of cisplatin ( P  < 0.05), increased cisplatin‐induced apoptosis ( P  < 0.05), and decreased EMT ( P  < 0.05) compared with high  HOXA13  expressed cells. In low  HOXA13  expressed cells, cleaved caspase‐3 and cleaved PARP expression induced by cisplatin increased, while expression of E‐cadherin and Snail protein, markers of EMT, was upregulated and downregulated, respectively. EMT decreased in low  HOXA13  expressed cells.    Conclusion  High  HOXA13  expression was associated with inferior tumor regression grade and poor overall survival in ESCC patients treated with neoadjuvant chemotherapy.  HOXA13  increased cisplatin‐resistance and promoted EMT in ESCC cells.

Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy