Predictive Biomarkers for 5-fluorouracil and Oxaliplatin-based Chemotherapy in Gastric Cancers Via Profiling of Patient-derived Xenografts

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Aug 11

PMID 34376661

Citations 18

Authors

Deukchae Na

Jeesoo Chae

Sung-Yup Cho

Wonyoung Kang

Ahra Lee

Seoyeon Min

Jinjoo Kang

Min Jung Kim

Jaeyong Choi

Woochan Lee

Dongjin Shin

Ahrum Min

Yu-Jin Kim

Kyung-Hun Lee

Tae-Yong Kim

Yun-Suhk Suh

Seong-Ho Kong

Hyuk-Joon Lee

Woo-Ho Kim

Hansoo Park

Seock-Ah Im

Han-Kwang Yang

Charles Lee

Jong-Il Kim

Affiliations

Soon will be listed here.

Abstract

Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both cancer cells and the tumor microenvironment (TME). We develop a 30-gene prediction model to determine the responsiveness to 5-FU and oxaliplatin-based chemotherapy and confirm the significant poor survival outcomes among cases classified as non-responder-like in three independent GC cohorts. Our study may inform clinical decision-making when designing treatment strategies.

Citing Articles

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