lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

A Novel TNM Assessing System for Predicting the Prognosis and Immunotherapy Response of Gastric Cancer

50 Pages Posted: 12 Apr 2019

See all articles by Siheng Lin

Siheng Lin

Southern Medical University - Department of Oncology

Rui Zhou

Southern Medical University - Department of Oncology

Dongqiang Zeng

Southern Medical University - Department of Oncology

Jiani Wu

Southern Medical University - Department of Oncology

Jianhua Wu

Southern Medical University - Department of Oncology

Jingwen Zhang

Southern Medical University

Huiying Sun

Southern Medical University - Department of Oncology

Shaowei Zhu

Southern Medical University - Department of Oncology

Min Shi

Southern Medical University - Department of Oncology

Jianping Bin

Southern Medical University - State Key Laboratory of Organ Failure Research

Yulin Liao

Southern Medical University

Wangjun Liao

Southern Medical University - Department of Oncology

More...

Abstract

Background: The classical diagnostic method for the prognosis prediction of gastric cancer is imprecise. Thus, tools that can precisely predict the prognosis of gastric cancer subtypes and guide treatment strategies are needed.

Methods: Using publicly available data from The Cancer Genome Atlas and Gene Expression Omnibus, we established tumor-noncoding RNA-microenvironment type (TNM) scores to define a combination of signatures that reflect the expression levels of tumor-related protein-coding genes (tumor score), tumor-related noncoding genes (NC score), and the cellular and stromal composition of the tumor microenvironment (TME score). These signatures were used to predict the prognosis of gastric cancer patients and the therapeutic effect of immunotherapy on gastric cancer.

Results: Based on TNM scores, gastric cancer patients were divided into three subgroups and Kaplan-Meier survival curves revealed significant differences among the subgroups (P < 0.001). Tumor score was positively associated with the epithelial-mesenchymal transition signaling pathway and transforming growth factor-beta signaling pathway and negatively associated with DNA damage repair. The TME score showed opposite results and was also positively associated with cytotoxic T-cells and immune check-points. We also explored the predictive ability of TNM scores for the effectiveness of anti-PD-1/PD-L1 treatment. Receiver operating characteristic curves showed that a combination of TME score, tumor score, and tumor mutation burden could predict the treatment effect well (area under the curve = 0.708).

Conclusion: Our study showed that the TNM scores could be used as a robust predicting tool for the prognosis of gastric cancer and the treatment effects of check-point inhibitors.

Funding: This study was supported by the National Natural Science Foundation of China (No. 81772580, and 81811530024 to Wangjun Liao); Guangzhou Planed Project of Science and Technology (No. 201803010070 to Wangjun Liao).

Declaration of Interest: The authors declare that they have no competing interests.

Keywords: Gastric cancer, prognosis, tumor microenvironment, noncoding RNA, immunotherapy

Suggested Citation

Lin, Siheng and Zhou, Rui and Zeng, Dongqiang and Wu, Jiani and Wu, Jianhua and Zhang, Jingwen and Sun, Huiying and Zhu, Shaowei and Shi, Min and Bin, Jianping and Liao, Yulin and Liao, Wangjun, A Novel TNM Assessing System for Predicting the Prognosis and Immunotherapy Response of Gastric Cancer (April 10, 2019). Available at SSRN: https://ssrn.com/abstract=3369743 or http://dx.doi.org/10.2139/ssrn.3369743

Siheng Lin

Southern Medical University - Department of Oncology

Guangzhou, Guangdong
China

Rui Zhou

Southern Medical University - Department of Oncology

Guangzhou, Guangdong
China

Dongqiang Zeng

Southern Medical University - Department of Oncology

Guangzhou, Guangdong
China

Jiani Wu

Southern Medical University - Department of Oncology

Guangzhou, Guangdong
China

Jianhua Wu

Southern Medical University - Department of Oncology

Guangzhou, Guangdong
China

Jingwen Zhang

Southern Medical University

Guangzhou, Guangdong Province
China

Huiying Sun

Southern Medical University - Department of Oncology

Guangzhou, Guangdong
China

Shaowei Zhu

Southern Medical University - Department of Oncology

Guangzhou, Guangdong
China

Min Shi

Southern Medical University - Department of Oncology

Guangzhou, Guangdong
China

Jianping Bin

Southern Medical University - State Key Laboratory of Organ Failure Research

Guangzhou, Guangdong Province
China

Yulin Liao

Southern Medical University

Guangzhou, Guangdong Province
China

Wangjun Liao (Contact Author)

Southern Medical University - Department of Oncology ( email )

Guangzhou, Guangdong
China

Click here to go to TheLancet.com

Paper statistics

Abstract Views
174
Downloads
15