Development and validation of an inflammatory response-related gene and clinical factor-based signature for predicting prognosis in gastric cancer

Li, Suihui1; Zhu, Jinfeng2,3; Zhu, Tengfei3; Xu, Yu3; Chen, Wenxi3; Zhou, Qiaoxia3; Wang, Guoqiang3; Li, Leo3; Han, Yusheng3; Xu, Chunwei4; Wang, Wenxian5; Cai, Shangli3; Xu, Ruilian6,8; Shao, Yu7,9

2023-04-29

10.21037/jgo-23-128

JOURNAL OF GASTROINTESTINAL ONCOLOGY   Impact Factor & Quartile

2078-6891

2219-679X

Background: Gastric cancer (GC) is an aggressive disease that requires prognostic tools to aid in clinical management. The prognostic power of clinical features is unsatisfactory, which might be improved by combining mRNA-based signatures. Inflammatory response is widely associated with cancer development and treatment response. It is worth exploring the prognostic performance of inflammatory-related genes plus clinical factors in GC. Methods: An 11-gene signature was trained using the least absolute shrinkage and selection operator (LASSO) based on the messenger RNA (mRNA) and overall survival (OS) data of The Cancer Genome Atlas-stomach adenocarcinoma (TCGA-STAD) cohort. A nomogram was established using the signature and clinical factors with a significant linkage with OS and was validated in 3 independent cohorts (GSE15419, GSE13861, and GSE66229) via calculating the area under the receiver operator characteristic curve (AUC). The association between the signature and immunotherapy efficacy was explored in the ERP107734 cohort. Results: A high risk score was associated with shorter OS in both the training and the validation sets (the AUC for 1-, 3-, 5-year in TCGA-STAD cohort: 0.691, 0.644, and 0.707; GSE15459: 0.602, 0.602, and 0.650; GSE13861: 0.648, 0.611, and 0.647; GSE66229: 0.661, 0.630, and 0.610). Its prognostic power was improved by combining clinical factors including age, sex, and tumor stage (the AUC for 1-, 3-, 5-year in TCGA-STAD cohort: 0.759, 0.706, and 0.742; GSE15459: 0.773, 0.786, and 0.803; GSE13861: 0.749, 0.881, and 0.795; GSE66229: 0.773, 0.735, and 0.722). Moreover, a low-risk score was associated with a favorable response to pembrolizumab monotherapy in the advanced setting (AUC =0.755, P=0.010). Conclusions: In GCs, the inflammatory response-related gene-based signature was related to immunotherapy efficacy, and its risk score plus clinical features yielded robust prognostic power. With prospective validation, this model may improve the management of GC by enabling risk stratification and the prediction of response to immunotherapy.

Gastric cancer (GC) prognosis estimation inflammatory response tumor microenvironment

SCI

English

Corresponding

2018 Entrepreneurial Leading Talent of Guangzhou Huangpu District and Guangzhou Development District[2022-L023]

Oncology ; Gastroenterology & Hepatology

Oncology ; Gastroenterology & Hepatology

WOS:001042474100010

AME PUBLISHING COMPANY

Web of Science

1.Guangzhou Univ Tradit Chinese Med, Affiliated Hosp 1, Dept Oncol, Guangzhou, Peoples R China
2.Fujian Med Univ, Quanzhou Hosp 1, Dept Internal Med Oncol, Quanzhou, Peoples R China
3.Burning Rock Biotech, Guangzhou, Peoples R China
4.Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou, Peoples R China
5.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Dept Clin Trial, Hangzhou, Peoples R China
6.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Clin Med Coll 2,Affiliated Hosp 1, Shenzhen, Peoples R China
7.Fujian Med Univ, Dept Pathol, Union Hosp, Fuzhou, Peoples R China
8.Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Dept Oncol,Shenzhen Peoples Hosp,Clin Med Coll 2, 1017 Dongmen North Rd, Shenzhen 518020, Peoples R China
9.Fujian Med Univ, Dept Pathol, Union Hosp, 29 Xinquan Rd, Fuzhou, Peoples R China

Li, Suihui,Zhu, Jinfeng,Zhu, Tengfei,et al. Development and validation of an inflammatory response-related gene and clinical factor-based signature for predicting prognosis in gastric cancer[J]. JOURNAL OF GASTROINTESTINAL ONCOLOGY,2023,14(2).

Li, Suihui.,Zhu, Jinfeng.,Zhu, Tengfei.,Xu, Yu.,Chen, Wenxi.,...&Shao, Yu.(2023).Development and validation of an inflammatory response-related gene and clinical factor-based signature for predicting prognosis in gastric cancer.JOURNAL OF GASTROINTESTINAL ONCOLOGY,14(2).

Li, Suihui,et al."Development and validation of an inflammatory response-related gene and clinical factor-based signature for predicting prognosis in gastric cancer".JOURNAL OF GASTROINTESTINAL ONCOLOGY 14.2(2023).