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

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.

Volatilomic Signatures of AGS and SNU-1 Gastric Cancer Cell Lines

“…Both cell lines show mutations of PIK3CA, which encodes for phosphatidylinositol-4,5-bisphosphate 3-kinase and plays a critical role in the PI3K/AKT signaling pathway regulating cell growth and proliferation [55]. Another gene which is mutated in both cell lines is APC, which is a tumor suppressor that is among the five most frequently affected genes in gastric cancer [56], and it serves as a regulator of cell proliferation. There are also differences concerning mutations of characteristic genes for gastric cancer between the two cell lines.…”

Liquid Biopsy: An Emerging Diagnostic, Prognostic, and Predictive Tool in Gastric Cancer

“…It aims to predict the prognosis and adjust the treatment intensity for optimal survival rates through individual treatment for GC. Several studies have predicted the prognosis of patients with GC using blood-based biomarkers ( Table 3 ) [ 33 40 69 74 82 86 88 89 90 91 92 93 94 95 96 97 98 99 100 101 ].…”

Landscape of Genetic Mutations in Appendiceal Cancers

“…TP53 was the most common mutated gene (55%), and MET had a higher frequency of mutations (15%). They concluded that TP53 mutation and MET amplification in circulating-tumor DNA could predict the disease progression of advanced gastric cancer patients [54]. MET amplification in circulating-tumor DNA could predict the disease progression of advanced gastric cancer patients [54].…”