Clinical and genetic characteristics in pancreatic cancer from Chinese patients revealed by whole exome sequencing

Yonggang He; Wen Huang; Yichen Tang; Yuming Li; Xuehui Peng; Jing Li; Jing Wu; Nan You; Ling Li; Chuang Liu; Lu Zheng; Xiaobing Huang

doi:10.3389/fonc.2023.1167144

Clinical and genetic characteristics in pancreatic cancer from Chinese patients revealed by whole exome sequencing

Front Oncol. 2023 May 29:13:1167144. doi: 10.3389/fonc.2023.1167144. eCollection 2023.

Authors

Yonggang He¹, Wen Huang¹, Yichen Tang¹, Yuming Li¹, Xuehui Peng¹, Jing Li¹, Jing Wu¹, Nan You¹, Ling Li², Chuang Liu², Lu Zheng¹, Xiaobing Huang¹

Affiliations

¹ Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing, China.
² Department of Medicine, Yinfeng Gene Technology Co Ltd, Jinan, China.

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide, mostly as a result of the absence of early detection and specific treatment solutions. Consequently, identifying mutational profiles and molecular biomarkers is essential for increasing the viability of precision therapy for pancreatic cancer.

Methods: We collected blood and tumor tissue samples from 47 Chinese pancreatic cancer patients and used whole-exome sequencing (WES) to evaluate the genetic landscape.

Results: Our results showed the most frequently somatic alteration genes were KRAS (74.5%), TP53(51.1%), SMAD4 (17%), ARID1A (12.8%), CDKN2A (12.8%), TENM4 (10.6%), TTN (8.5%), RNF43(8.5%), FLG (8.5%) and GAS6 (6.4%) in Chinese PDAC patients. We also found that three deleterious germline mutations (ATM c.4852C>T/p. R1618*, WRN c.1105C>T/p. R369*, PALB2 c.2760dupA/p. Q921Tfs*7) and two novel fusions (BRCA1-RPRML, MIR943 (intergenic)-FGFR3). When compared to the Cancer Genome Atlas (TCGA) database, there is a greater mutation frequency of TENM4 (10.6% vs. 1.6%, p = 0.01), GAS6(6.4% vs. 0.5%, p = 0.035), MMP17(6.4% vs. 0.5%, p = 0.035), ITM2B (6.4% vs. 0.5%, p = 0.035) and USP7 (6.4% vs. 0.5%, p= 0.035) as well as a reduced mutation frequency of SMAD4 (17.0% vs. 31.5%, p = 0.075) and CDKN2A (12.8% vs. 47.3%, p < 0.001) were observed in the Chinese cohort. Among the 41 individuals examined for programmed cell death ligand 1(PD-L1) expression, 15 (36.6%) had positive PD-L1 expression. The median tumor mutational burden (TMB) was found to be 12muts (range, 0124). The TMB index was higher in patients with mutant-type KRAS MUT/TP53 MUT (p < 0.001), CDKN2A (p = 0.547), or SMAD4 (p = 0.064) compared to patients with wild-type KRAS/TP53, CDKN2A, or SMAD4.

Conclusions: We exhibited real-world genetic traits and new alterations in Chinese individuals with cancer of the pancreas, which might have interesting implications for future individualized therapy and medication development.

Keywords: KRAS; PD-L1; TMB; gene mutation; pancreatic ductal adenocarcinoma (PDAC); whole-exome sequencing.

Grants and funding

This research was funded by Chongqing Natural Science Foundation project (CSTB2022NSCQ-MSX0172); Basic Science and Frontier Technology Research Project of Chongqing Science and Technology Commission (grant number cstc2017jcyjAX0348) and Chongqing Technology Innovation and Application Demonstration (Social and Livelihood General) Project (cstc2018jscx-msybX0043).