Prognostic Value of Tumor Mutation Burden in Patients with Advanced Gastric Cancer Receiving First-line Chemotherapy

Overview

Journal Front Oncol

Specialty Oncology

Date 2023 Jan 23

PMID 36686739

Authors

Xiao-Peng Duan

Ke Liu

Xiao-Dong Jiao

Bao-Dong Qin

Bing Li

Xi He

Yan Ling

Ying Wu

Shi-Qi Chen

Yuan-Sheng Zang

Affiliations

Soon will be listed here.

Abstract

Background: Tumor mutation burden (TMB) is a promising biomarker positively associated with the benefit of immunotherapy and that might predict the outcome of chemotherapy. We described the prognostic value of TMB in advanced gastric cancer and explored the underlying mechanism.

Methods: We enrolled 155 TMB-evaluated advanced gastric cancer patients and analyzed the relationship between clinicopathological characteristics and both overall survival (OS) and progression-free survival (PFS) among 40 patients treated with first-line chemotherapy. We further verified the distribution of TMB and analyzed the potential mechanism underlying the prognosis based on The Cancer Genome Atlas (TCGA) database.

Results: Among the 155 patients, 29 (18.7%) were TMB-high (TMB ≥ 10), roughly the same as the proportion in the TCGA data. Of the 40 patients receiving first-line chemotherapy, the median OS (7.9 . 12.1 months; HR 3.18; = 0.0056) and PFS (4.4 . 6.2 months; HR 2.94; = 0.0099) of the tissue-tested TMB (tTMB)-high patients were inferior to those of the tTMB-low patients. Similarly, unfavorable median OS (9.9 . 12.1 months; HR 2.11; = 0.028) and PFS (5.3 . 6.5 months; HR 2.49; = 0.0054) were shown in the blood-tested TMB (bTMB)-high than in the bTMB-low patients. The Cox analysis demonstrated that both tTMB-high and bTMB-high were significant independent predictors of dreadful OS and PFS. The differentially expressed genes (DEGs) according to TMB status were most significantly enriched in the downregulated metabolic pathway among the TMB-high patients.

Conclusions: TMB-high advanced gastric cancer patients accounted for around one-sixth and had a poorer prognosis than TMB-low patients when treated with first-line chemotherapy. The potential mechanism might be the downregulated metabolic activity in TMB-high patients.

Citing Articles

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A machine learning-based radiomics model for prediction of tumor mutation burden in gastric cancer.

Ma T, Zhang Y, Zhao M, Wang L, Wang H, Ye Z Front Genet. 2023; 14:1283090.

PMID: 38028587 PMC: 10657897. DOI: 10.3389/fgene.2023.1283090.

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