Transcobalamin I: a novel prognostic biomarker of neoadjuvant chemotherapy in locally advanced hypopharyngeal squamous cell cancers.
Transcobalamin I: a novel prognostic biomarker of neoadjuvant chemotherapy in locally advanced hypopharyngeal squamous cell cancers.
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钴胺素 I：局部晚期下咽鳞状细胞癌新辅助化疗的新型预后生物标志物
DOI：
10.2147/ott.s166514
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发表时间：
2018
影响因子：
4
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Wang Y;Yue C;Fang J;Gong L;Lian M;Wang R;Feng L;Ma H;Ma Z;Liu H
下咽鳞状细胞癌是一种侵袭性头颈部鳞状细胞癌，预后较差。新辅助化疗（NACT）联合放化疗对HPSCC的治疗效果更好。鉴别预测性生物标志物对于改善从NACT中获益最多的患者的选择是至关重要的。本研究的目的是探讨转钴胺素I （TCN1）是否可以作为HPSCC中NACT的一种新的预测性生物标志物。方法收集102例原发性局部晚期HPSCC患者的活检标本。应用定量聚合酶链反应和免疫组织化学分别分析TCN1 mRNA和蛋白表达水平。采用单因素Kaplan-Meier生存分析和多因素协变量调整分析来评估TCN1表达、化疗敏感性和临床结果之间的关系。此外，我们在HPSCC FaDu细胞中通过小干扰RNA （siRNA）敲低TCN1， MTT法检测TCN1敲低对顺铂毒性的影响，Western blotting检测顺铂诱导的细胞凋亡。结果TCN1在NACT敏感组的蛋白水平（p=0.013）和mRNA水平（p<0.001）均显著低于非敏感组，提示TCN1表达水平低预示着NACT治疗效果更好。此外，TCN1是晚期HPSCC患者总生存期（p=0.047）和无病生存期（p=0.05）的独立预后生物标志物。此外，体外实验表明，使用siRNA对TCN1进行基因沉默可使FaDu细胞对顺铂治疗增敏，并增加细胞凋亡。结论TCN1低表达可能是预测局部晚期HPSCC患者NACT敏感性和临床预后的一种新的预后生物标志物。
Background Hypopharyngeal squamous cell carcinoma (HPSCC) is an aggressive head and neck squamous cell carcinoma with poor prognosis. Neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy could provide better efficacy in HPSCC treatment. Identification of predictive biomarkers is critically needed to improve selection of patients who derive the most benefit from NACT. The aim of this study was to investigate whether transcobalamin I (TCN1) could be a novel predictive biomarker for NACT in HPSCC. Methods We collected biopsy specimens from 102 patients with primary locally advanced HPSCC. Messenger RNA (mRNA) and protein expression levels of TCN1 were analyzed using quantitative polymerase chain reaction and immunohistochemistry, respectively. The relationship between TCN1 expression, chemotherapy sensitivity, and clinical outcome was assessed using univariate Kaplan–Meier survival analyses and multivariate analysis with covariate adjustments. Furthermore, we knocked down TCN1 by small interfering RNA (siRNA) in HPSCC cell FaDu, tested the effects of TCN1 knockdown on cisplatin toxicity by MTT assay, and detected cisplatin-induced apoptosis by Western blotting. Results TCN1 expression was significantly lower in NACT-sensitive patients than nonsensitive patients at protein level (p=0.013) and mRNA level (p<0.001), indicating that low TCN1 expression predicts better NACT treatment response. Furthermore, TCN1 was an independent prognostic biomarker for both overall survival (p=0.047) and disease-free survival (p=0.05) in advanced HPSCC patients. In addition, in vitro experiments showed that genetic silencing of TCN1 using siRNA sensitized FaDu cells to cisplatin treatment with increased cell apoptosis. Conclusion Low expression of TCN1 might be a novel prognostic biomarker for predicting NACT sensitivity and clinical outcome in local advanced HPSCC patients.