DNA跨损伤合成聚合酶η在头颈部鳞状细胞癌中的表达预示着对吉西他滨和顺铂化疗的耐药性。
Expression of DNA translesion synthesis polymerase η in head and neck squamous cell cancer predicts resistance to gemcitabine and cisplatin-based chemotherapy.
作者信息
Zhou Wendi, Chen Yih-wen, Liu Xiyong, Chu Peiguo, Loria Sofia, Wang Yafan, Yen Yun, Chou Kai-Ming
机构信息
Department of Pathology, St. Luke's-Roosevelt Hospital Center, Affiliated Hospital of Columbia University College of Physicians and Surgeons, New York, New York, United States of America.
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
出版信息
PLoS One. 2013 Dec 20;8(12):e83978. doi: 10.1371/journal.pone.0083978. eCollection 2013.
PURPOSE
The development of resistance against anticancer drugs has been a persistent clinical problem for the treatment of locally advanced malignancies in the head and neck mucosal derived squamous cell carcinoma (HNSCC). Recent evidence indicates that the DNA translesion synthesis (TLS) polymerase η (Pol η; hRad30a gene) reduces the effectiveness of gemcitabine/cisplatin. The goal of this study is to examine the relationship between the expression level of Pol η and the observed resistance against these chemotherapeutic agents in HNSCC, which is currently unknown.
METHODS
Sixty-four mucosal derived squamous cell carcinomas of head and neck (HNSCC) from 1989 and 2007 at the City of Hope National Medical Center (Duarte, CA) were retrospectively analyzed. Pretreatment samples were immunostained with anti-Pol η antibody and the correlation between the expression level of Pol η and clinical outcomes were evaluated. Forty-nine cases treated with platinum (n=40) or gemcitabine (n=9) based chemotherapy were further examined for Pol η expression level for comparison with patient response to chemotherapy.
RESULTS
The expression of Pol η was elevated in 67% of the head and neck tumor samples. Pol η expression level was significantly higher in grade 1 to grade 2 tumors (well to moderately differentiated). The overall benefit rate (complete response+ partial response) in patients treated with platinum and gemcitabine based chemotherapy was 79.5%, where low Pol η level was significantly associated with high complete response rate (p=0.03), although not associated with overall survival. Furthermore, no significant correlation was observed between Pol η expression level with gender, age, tobacco/alcohol history, tumor stage and metastatic status.
CONCLUSIONS
Our data suggest that Pol η expression may be a useful prediction marker for the effectiveness of platinum or gemcitabine based therapy for HNSCC.
目的
对于头颈部黏膜来源的鳞状细胞癌（HNSCC）局部晚期恶性肿瘤的治疗，抗癌药物耐药性的产生一直是个棘手的临床问题。最近有证据表明，DNA跨损伤合成（TLS）聚合酶η（Pol η；hRad30a基因）会降低吉西他滨/顺铂的疗效。本研究的目的是探讨Pol η的表达水平与HNSCC中观察到的对这些化疗药物的耐药性之间的关系，目前这一关系尚不清楚。
方法
回顾性分析了1989年至2007年在希望之城国家医疗中心（加利福尼亚州杜阿尔特）的64例头颈部黏膜来源的鳞状细胞癌（HNSCC）。用抗Pol η抗体对预处理样本进行免疫染色，并评估Pol η表达水平与临床结果之间的相关性。对49例接受铂类（n = 40）或吉西他滨（n = 9）化疗的病例进一步检测Pol η表达水平，以与患者对化疗的反应进行比较。
结果
67%的头颈部肿瘤样本中Pol η表达升高。在1级至2级肿瘤（高分化至中分化）中，Pol η表达水平显著更高。接受铂类和吉西他滨化疗的患者的总有效率（完全缓解+部分缓解）为79.5%，其中低Pol η水平与高完全缓解率显著相关（p = 0.03），尽管与总生存期无关。此外，未观察到Pol η表达水平与性别、年龄、吸烟/饮酒史、肿瘤分期和转移状态之间存在显著相关性。
结论
我们的数据表明，Pol η表达可能是HNSCC中铂类或吉西他滨治疗疗效的有用预测标志物。
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