Park Joo Kyung, Kim Hyemin, Son Dae-Soon, Kim Nayoung K D, Sung Young Kyung, Cho Minseob, Lee Chung, Noh Dong Hyo, Lee Se-Hoon, Lee Kyu Taek, Lee Jong Kyun, Jang Kee-Taek, Park Woong-Yang, Lee Kwang Hyuck
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea.
Cancers (Basel). 2021 Jun 3;13(11):2791. doi: 10.3390/cancers13112791.
The aim of this study was to investigate the clinical utility of minimal specimens acquired from endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) and perform targeted deep sequencing as a prognosis prediction tool for pancreatic ductal adenocarcinoma (PDAC). A total of 116 specimens with pathologically confirmed PDAC via EUS-FNB were tested using CancerSCAN panel for a customized targeted deep sequencing. Clinical prognostic factors significantly associated with survival in PDACs were as follows: stage, tumor mass size, tumor location, metastasis, chemotherapy, and initial CA19-9 level. A total of 114 patients (98.3%) had at least a single genetic alteration, and no mutations were detected in two patients, although they were qualified for the targeted deep sequencing. The frequencies of major gene mutations responsible for PDACs were 90%, 31%, 77%, and 29%. A somatic point mutation of , copy number alteration of , and loss-of-function of were significantly associated genetic factors for overall survival. Moreover, point mutation was related to liver metastasis. Finally, a clinico-genomic model was developed to estimate the prognosis of patients with PDAC based on clinical parameters and genetic alterations affecting survival in patients; 20 single nucleotide variants and three copy number variations were selected. Targeted deep sequencing on minimal specimens of PDACs was performed, and it was applied to establish a clinico-genomic model for prognosis prediction.
本研究旨在探讨经内镜超声引导下细针穿刺活检（EUS-FNB）获取的微量样本的临床效用，并进行靶向深度测序，作为胰腺导管腺癌（PDAC）的预后预测工具。通过EUS-FNB获得的116例经病理证实为PDAC的样本，使用CancerSCAN panel进行定制的靶向深度测序。与PDAC患者生存显著相关的临床预后因素如下：分期、肿瘤肿块大小、肿瘤位置、转移、化疗和初始CA19-9水平。共有114例患者（98.3%）至少有一个基因改变，两名患者未检测到突变，尽管他们符合靶向深度测序的条件。导致PDAC的主要基因突变频率分别为90%、31%、77%和29%。 的体细胞点突变、 的拷贝数改变和 的功能丧失是与总生存显著相关的遗传因素。此外， 点突变与肝转移有关。最后，基于影响患者生存的临床参数和基因改变，开发了一种临床基因组模型来估计PDAC患者的预后；选择了20个单核苷酸变异和3个拷贝数变异。对PDAC的微量样本进行了靶向深度测序，并将其应用于建立预后预测的临床基因组模型。
