Smad4和p53突变对接受化疗的胰腺导管腺癌患者预后的影响。
Impact of Smad4 and p53 mutations on the prognosis of patients with pancreatic ductal adenocarcinoma undergoing chemotherapy.
发表日期：2023 Aug 18
作者：
Ken Kamata, Mamoru Takenaka, Naoshi Nishida, Akane Hara, Yasuo Otsuka, Hidekazu Tanaka, Shunsuke Omoto, Kosuke Minaga, Kentaro Yamao, Yasutaka Chiba, Kazuko Sakai, Kazuto Nishio, Tomohiro Watanabe, Masatoshi Kudo
来源：
GENES & DEVELOPMENT
摘要：
本前瞻性队列研究评估了使用内镜超声引导的细针活检（EUS-FNB）样本进行微组织全面突变分析的可行性。2018年1月至2019年1月，在近畿大学医院接连出现的疑似胰腺癌的50名患者被纳入研究。通过EUS-FNB获取每个肿瘤的癌组织，并进行组织学检查和突变分析。主要终点是使用深度测序进行综合癌症检测的EUS-FNB标本的收集率。次要终点是评估化疗患者的疾病控制组与进展性疾病组之间的临床病史和基因变异。使用深度测序的综合癌症检测的EUS-FNB标本的收集率为93.6%。对最初接受全身化疗的25例胰腺癌患者进行了癌症检测。p53和Smad4的突变与最初评估的疾病控制呈正相关和负相关。携带p53突变但没有Smad4突变的15名患者的中位无进展时间为182.0天；而其他10名患者的中位无进展时间为92.5天，这种差异具有显著性（p=0.020）。EUS-FNB的组织样本适于突变分析。携带p53突变但没有Smad4突变的胰腺癌对化疗反应更好，预后更好。© 2023. 作者（代表日本临床肿瘤学会）独家授权。
This prospective cohort study evaluated the feasibility of using endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) samples for comprehensive mutational analysis of cancer-related genes using microtissues.Fifty patients with suspected pancreatic cancer presenting consecutively at the Kindai University Hospital between January 2018 and January 2019 were enrolled. Cancerous tissues from EUS-FNB were obtained from each tumor and subjected to histological examination and mutational analysis. The primary endpoint was the collection rate of EUS-FNB specimens suitable for comprehensive cancer panels using deep sequencing. Clinical history and genetic variations between the disease control and progressive disease groups of patients on chemotherapy were evaluated as secondary endpoints.The collection rate of EUS-FNB specimens suitable for comprehensive cancer panels using deep sequencing was 93.6%. The cancer panel was sequenced for 25 patients with pancreatic cancer treated initially with systemic chemotherapy. Mutation in p53 and Smad4 were positively and negatively associated, respectively, with disease control at the initial evaluation. The median time to progression in 15 patients with p53 and without Smad4 mutations was 182.0 days; whereas, it was 92.5 days in other 10 patients; this difference was significant (p = 0.020).Tissue samples from EUS-FNB were suitable for mutational analysis. Pancreatic cancers with p53 and without Smad4 mutations responded better to chemotherapy and had a better prognosis than those others.© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.