TP53 mutation and MET amplification in circulating tumor DNA analysis predict disease progression in patients with advanced gastric cancer

Jia Li; Zhaoyan Li; Yajie Ding; Yan Xu; Xiaohong Zhu; Nida Cao; Chen Huang; Mengmeng Qin; Feng Liu; Aiguang Zhao

doi:10.7717/peerj.11146

TP53 mutation and MET amplification in circulating tumor DNA analysis predict disease progression in patients with advanced gastric cancer

PeerJ. 2021 Apr 16:9:e11146. doi: 10.7717/peerj.11146. eCollection 2021.

Authors

Jia Li^#^{1

2}, Zhaoyan Li^#³, Yajie Ding¹, Yan Xu¹, Xiaohong Zhu¹, Nida Cao¹, Chen Huang⁴, Mengmeng Qin¹, Feng Liu¹, Aiguang Zhao¹

Affiliations

¹ Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China.
² Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, China.
³ Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China.
⁴ Department of General Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

^# Contributed equally.

Abstract

Background: Gastric cancer (GC) is a heterogeneous disease that encompasses various molecular subtypes. The molecular mutation characteristics of circulating tumor DNA (ctDNA) in advanced gastric cancer (AGC), especially the clinical utility of TP53 mutation and MET amplification in ctDNA need to be further explored.

Objectives: The aim of this study was mainly to assess the clinical utility of TP53 mutation and MET amplification in ctDNA as biomarkers for monitoring disease progression of AGC.

Patients and methods: We used multigene NGS-panel technology to study the characteristics of ctDNA gene mutations and screen the key mutant genes in AGC patients. The Kaplan-Meier method was used to calculate the survival probability and log-rank test was used to compare the survival curves of TP53 mutation and MET amplification in ctDNA of AGC patients. The survival time was set from the blood test time to the follow-up time to observe the relationship between the monitoring index and tumor prognosis.

Results: We performed mutation detection on ctDNA in 23 patients with AGC and identified the top 20 mutant genes. The five most frequently mutated genes were TP53 (55%), EGFR (20%), ERBB2 (20%), MET (15%) and APC (10%). TP53 was the most common mutated gene (55%) and MET had a higher frequency of mutations (15%) in our study. Kaplan-Meier analysis showed that patients with TP53 mutant in ctDNA had shorter overall survival (OS) than these with TP53 wild (P < 0.001). The Allele frequency (AF) of TP53 mutations in patient number 1 was higher in the second time (0.94%) than in the first time (0.36%); the AF of TP53 mutations in patient number 16 was from scratch (0∼0.26%). In addition, the AF of TP53 mutations in patients who survive was relatively low (P = 0.047). Simultaneously, Kaplan-Meier analysis showed that patients with MET amplification also had shorter OS than these with MET without amplification (P < 0.001).

Conclusion: TP53 and MET are the two common frequently mutant genes in ctDNA of AGC patients.TP53 mutation and MET amplification in ctDNA could predict disease progression of AGC patients.

Keywords: Advanced gastric cancer; Circulating tumor DNA; Disease progression; MET amplification; TP53 mutation.

Grants and funding

The research was supported by the Ministry of Science and Technology National Key Research and Development Program (2017YFC1700605), the National Health and Family Planning Commission’s “Major New Drug Creation” Science and Technology Major Project (2017ZX09304-001), the National Traditional Chinese Medicine Administration National TCM Clinical Research Base Business Construction Research Project (JDZX2015068) and the Key R&D and promotion projects in Henan Province (212102310342). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.