Somatic Mutation Profiling of Intrahepatic Cholangiocarcinoma: Comparison between Primary and Metastasis Tumor Tissues

Shi-Feng Xu; Yuan Guo; Xin Zhang; Xiao-Dan Zhu; Ning Fan; Zhi-Lei Zhang; Gui-Bing Ren; Wei Rao; Yun-Jin Zang

doi:10.1155/2020/5675020

Somatic Mutation Profiling of Intrahepatic Cholangiocarcinoma: Comparison between Primary and Metastasis Tumor Tissues

J Oncol. 2020 Sep 17:2020:5675020. doi: 10.1155/2020/5675020. eCollection 2020.

Authors

Shi-Feng Xu¹, Yuan Guo², Xin Zhang³, Xiao-Dan Zhu⁴, Ning Fan², Zhi-Lei Zhang⁵, Gui-Bing Ren⁶, Wei Rao⁷, Yun-Jin Zang⁴

Affiliations

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.
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.

Abstract

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.