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Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy.

ABSTRACT: 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?

SUBMITTER: Shi Q

PROVIDER: S-EPMC6026615 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy.

Shi Qi Q Shen Luyan L Dong Bin B Fu Hao H Kang Xiaozheng X Dai Liang L Yang Yongbo Y Yan Wanpu W Chen Ke-Neng KN

Thoracic cancer 20180514 7

<h4>Background</h4>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.<h4>Methods</h4>One hundred thirty-one ESCC patients who received neoadjuvant chemotherapy were enrolled. HOXA13 expression was examined by immunohistochemistry. RNA interfe ...[more]

PMID: 29757528

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Project description:BackgroundThe literature regarding esophageal fistula after definitive concurrent chemotherapy and intensity modulated radiotherapy (IMRT) for esophageal squamous cell carcinoma (ESCC) remains lacking. We aimed to investigate the risk factors of esophageal fistula among ESCC patients undergoing definitive concurrent chemoradiotherapy (CCRT) via IMRT technique.MethodsA total of 129 consecutive ESCC patients receiving definitive CCRT with IMRT between 2008 and 2018 were reviewed. The cumulative incidence of esophageal fistula and survival of patients were estimated by the Kaplan-Meier method and compared between groups by the log-rank test. The risk factors of esophageal fistula were determined with multivariate Cox proportional hazards regression analysis.ResultsMedian follow-up was 14.9 months (IQR, 7.0-28.8). Esophageal perforation was identified in 20 (15.5%) patients, resulting in esophago-pleural fistula in nine, esophago-tracheal fistula in seven, broncho-esophageal fistula in two, and aorto-esophageal fistula in two patients. The median interval from IMRT to the occurrence of esophageal fistula was 4.4 months (IQR, 3.3-10.1). Patients with esophageal fistula had an inferior median overall survival (10.0 vs. 17.2 months, p = 0.0096). T4 (HR, 3.776; 95% CI, 1.383-10.308; p = 0.010) and esophageal stenosis (HR, 2.601; 95% CI, 1.053-6.428; p = 0.038) at baseline were the independent risk factors for esophageal fistula. The cumulative incidence of esophageal fistula was higher in patients with T4 (p = 0.018) and pre-treatment esophageal stenosis (p = 0.045). There was a trend toward better survival after esophageal fistula among patients receiving repair or stenting for the fistula than those only undergoing conservative treatments (median survival, 5.9 vs. 0.9 months, p = 0.058).ConclusionsT4 and esophageal stenosis at baseline independently increased the risk of esophageal fistula in ESCC treated by definitive CCRT with IMRT. There existed a trend toward improved survival after the fistula among patients receiving repair or stenting for esophageal perforation.

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Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy.

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Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy.

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