Multi-omics characterization of molecular features of gastric cancer correlated with response to neoadjuvant chemotherapy.

Science Advances
Ziyu LiJiafu Ji

Abstract

Neoadjuvant chemotherapy is a common treatment for patients with gastric cancer. Although its benefits have been demonstrated, neoadjuvant chemotherapy is underutilized in gastric cancer management, because of the lack of biomarkers for patient selection and a limited understanding of resistance mechanisms. Here, we performed whole-genome, whole-exome, and RNA sequencing on 84 clinical samples (including matched pre- and posttreatment tumors) from 35 patients whose responses to neoadjuvant chemotherapy were rigorously defined. We observed increased microsatellite instability and mutation burden in nonresponse tumors. Through comparisons of response versus nonresponse tumors and pre- versus posttreatment samples, we found that C10orf71 mutations were associated with treatment resistance, which was supported by drug response data and potentially through inhibition of cell cycle, and that MYC amplification correlated with treatment sensitivity, whereas MDM2 amplification showed the opposite pattern. Neoadjuvant chemotherapy also reshapes tumor-immune signaling and microenvironment. Our study provides a critical basis for developing precision neoadjuvant regimens.

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Citations

Oct 3, 2020·Frontiers in Molecular Biosciences·Xiao-Jing ShiBoyang Ji
Feb 10, 2021·Cancer Research·Omer AnUNKNOWN Singapore Gastric Cancer Consortium (SGCC)
Jul 25, 2021·Cancers·Fereshteh Izadi On Behalf Of Occams
Aug 19, 2021·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Ziyu LiJiafu Ji

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Methods Mentioned

BETA
biopsy
RNA-seq
proteomic profiling
PCR
protein array

Software Mentioned

- FREEC
TIMER
Wheeler Aligner
HotNet2
SuperCurve
Control
GISTIC2
Tumor IMmune Estimation Resource ( TIMER )
FREEC
MuSiC2

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