机构：[1]Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China[2]Liver Disease Center, THe Affiliated Hospital of Qingdao University, Qingdao, China[3]Origimed, Shanghai, China[4]Organ Transplant Center, THe Affiliated Hospital of Qingdao University, Qingdao, China[5]Department of Hepatobiliary Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, China临床科室肝胆外科河北医科大学第四医院[6]Oncology Department, Armed Police Characteristic Medical Center, Tianjin, China[7]Division of Hepatology, Liver Disease Center, Organ Transplantation Center,THe Affiliated Hospital of Qingdao University, Qingdao, China
Introduction. Intrahepatic cholangiocarcinoma (ICC) exhibited increasing incidence and mortality around the world, with a 35% five-year survival rate. In this study, the genetic alteration of primary ICC and metastasis ICC was exhibited to discover novel personalized treatment strategies to improve the clinical prognosis.Methods. Based on 153 primary and 49 metastasis formalin-fixed paraffin-embedded ICC samples, comprehensive genomic profiling was carried out.Results. In primary tumor samples (PSs) and metastasis tumor samples (MSs), the top alteration genes were TP53 (41.8% vs 36.7%), KRAS (30.7% vs 36.7%), and ARID1A (22.2% vs 14.2%). In the top 20 most frequent alteration genes, BRAF showed lower mutation frequency in MSs as compared to PSs (0 vs 11.1%,P=0.015), while LRP1B exhibited opposed trend (22.4% vs 10.4%,P=0.032). In PSs, patients with MSI-H showed all PDL1 negative, and patients with PDL1 positive exhibited MSS both in PSs and MSs. It was found that the Notch pathway had more alteration genes in MSI-H patients (P=0.027). Furthermore, the patients with mutated immune genes in PSs were more than that in MSs (28.8% vs 8.2%,P=0.003, odd ratio = 0.2). Interestingly, the platinum drug resistance pathway was only enriched by mutated genes of MSs.Conclusions. In this study, the identification of two meaningful mutated genes, BRAF and LRP1B, highly mutated immune gene harbored by primary ICC patients. Both in PSs and MSs, no patients with MSI-H showed PDL1 positive. The Notch pathway had more alteration genes in patients with MSI-H. And the enrichment of the platinum drug resistance pathway in MSs might offer reference for the novel therapeutic strategy of ICC.
基金：
THis work was supported by Jinan Science and Technology
Clinical Medicine Science and Technology Innovation Plan
(201907073).
第一作者机构：[1]Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
共同第一作者：
通讯作者：
通讯机构：[4]Organ Transplant Center, THe Affiliated Hospital of Qingdao University, Qingdao, China[7]Division of Hepatology, Liver Disease Center, Organ Transplantation Center,THe Affiliated Hospital of Qingdao University, Qingdao, China
推荐引用方式(GB/T 7714)：
Xu Shi-Feng,Guo Yuan,Zhang Xin,et al.Somatic Mutation Profiling of Intrahepatic Cholangiocarcinoma: Comparison between Primary and Metastasis Tumor Tissues[J].JOURNAL OF ONCOLOGY.2020,2020:doi:10.1155/2020/5675020.
APA：
Xu, Shi-Feng,Guo, Yuan,Zhang, Xin,Zhu, Xiao-Dan,Fan, Ning...&Zang, Yun-Jin.(2020).Somatic Mutation Profiling of Intrahepatic Cholangiocarcinoma: Comparison between Primary and Metastasis Tumor Tissues.JOURNAL OF ONCOLOGY,2020,
MLA：
Xu, Shi-Feng,et al."Somatic Mutation Profiling of Intrahepatic Cholangiocarcinoma: Comparison between Primary and Metastasis Tumor Tissues".JOURNAL OF ONCOLOGY 2020.(2020)
