Genomic alterations in STK11 can predict clinical outcomes in cervical cancer patients
Genomic alterations in STK11 can predict clinical outcomes in cervical cancer patients
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DOI：
10.1016/j.ygyno.2019.10.022
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发表时间：
2020-01-01
影响因子：
4.7
通讯作者：
Yoshida, Hiroshi
中科院分区：
文献类型：
--
作者：
Hirose, Sou;Murakami, Naoya;Yoshida, Hiroshi
目的：由于预后不良，宫颈癌是亚洲妇女癌症相关死亡的第四大常见原因。本研究旨在破译一组日本宫颈癌患者的基因组改变谱，以了解为什么某些患者受益于分子靶向治疗及其预后意义。方法：2008-2018年期间，154名宫颈癌患者在国家癌症中心医院接受了可能治愈的切除手术。使用Ion AmpliSeg (TM) Cancer Hotspot Panel v2分析基因组DNA样本。使用TaqMan法检测PIK3CA、ERBB2、PTEN和STKII拷贝数的改变。hpv阳性结果经基因组检测和原位杂交试验证实。结果：PIK3CA（36%）、STK11（16%）、PTEN（11%）、TP53（11%）和KRAS（8%）的基因组改变频率为0.5%。KRAS突变优先在腺癌患者中检测到，PIK3CA突变在鳞状细胞癌患者中的频率高于其他组织学类型的癌症。139/154例（90.3%）患者hpv阳性，hpv阴性标本中检测到TP53突变体。在本研究中，STK11基因改变患者的总生存率低于野生型STK11患者（风险比= 10.6,P = 0.0079）和TCGA数据集患者（风险比= 2.46,P = 0.029）。结论：超过三分之一的日本宫颈癌患者表现出分子靶向治疗的靶向突变。我们提出了STK11基因组改变的预后价值。(C) 2019 Elsevier Inc.版权所有。
Objective: Cervical cancer is the fourth most common cause of cancer-related deaths in Asian women, due to its poor prognosis. This study aimed to decipher genomic alteration profiles of a cohort of Japanese cervical cancer patients to understand why certain patients benefited from molecular targeted therapies and their prognostic significance.Methods: During 2008-2018, 154 cervical cancer patients underwent a potentially curative resection procedure at the National Cancer Center Hospital. Genomic DNA samples were analyzed using Ion AmpliSeg (TM) Cancer Hotspot Panel v2. Alterations in the copy number of PIK3CA, ERBB2, PTEN, and STKII were detected using the TaqMan assay. HPV-positive results were confirmed by genomic testing and in situ hybridization assay.Results: The frequency of genomic alterations in PIK3CA (36%), STK11 (16%), PTEN (11%), TP53 (11%), and KRAS (8%) was >5%. KRAS mutations were preferentially detected in patients with adenocarcinomas, and the frequency of PIK3CA mutations in patients with squamous cell carcinomas was higher than that in patients with other histological cancer types. HPV-positive results were observed in 139/154 (90.3%) patients, and TP53 mutants were detected in HPV-negative specimens. In this study, the overall survival of patients with genomic alterations in STK11 was worse than in patients with wild-type STK11 (hazard ratio = 10.6, P = 0.0079) and TCGA dataset (hazard ratio = 2.46, P = 0.029).Conclusions: More than one-third of Japanese cervical cancer patients exhibit mutations targeted by molecular targeted therapies. We have proposed the prognostic value of STK11 genomic alterations. (C) 2019 Elsevier Inc. All rights reserved.