A Five-gene Signature based on MicroRNA for Predicting Prognosis and Immunotherapy in Stomach Adenocarcinoma

Wang, Tianwei1; Chen, Piji2; Li, Tingting3; Li, Jianong3; Zhao, Dong3; Meng, Fanfei4; Zhao, Yujie5; Zheng, Zhendong3,6; Liu, Xuefei3,6

2024

10.2174/0109298673281631231127051017

CURRENT MEDICINAL CHEMISTRY   影响因子和分区

0929-8673

1875-533X

Aims We aimed to classify molecular subtypes and establish a prognostic gene signature based on miRNAs for the prognostic prediction and therapeutic response in Stomach adenocarcinoma (STAD).Background STAD is a common diagnosed gastrointestinal malignancy and its heterogeneity is a big challenge that influences prognosis and precision therapies. Present study was designed to classify molecular subtypes and construct a prognostic gene signature based on miRNAs for the prognostic prediction and therapeutic response in STAD.Objective The objective of this study is to investigate the molecular subtypes and prognostic model for STAD.Methods A STAD specific miRNA-messenger RNA (mRNA) competing endogenous RNA (ceRNA) network was generated using the RNA-Seq and miRNA expression profiles from The Cancer Genome Atlas (TCGA) database, in which miRNA-related mRNAs were screened. Molecular subtypes were then determined using miRNA-related genes. Through univariate Cox analysis and multivariate regression analysis, a prognostic model was established in GSE84437 Train dataset and validated in GSE84437 Test, TCGA, GSE84437 and GSE66229 datasets. Immunotherapy datasets were employed for assessing the performance of the risk model. Finally, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied to validate the expression of hub genes used for the risk score signature.Results We constructed a ceRNA network containing 84 miRNAs and 907 mRNAs and determined two molecular subtypes based on 26 genes from the intersection of TCGA-STAD and GSE84437 datasets. Subtype S2 had poor prognosis, lower tumor mutational burden, higher immune score and lower response to immunotherapy. Subtype S1 was more sensitive to Sorafenib, Pyrimethamine, Salubrinal, Gemcitabine, Vinorelbine and AKT inhibitor VIII. Next, a five-gene signature was generated and its robustness was validated in Test and external datasets. This risk model also had a good prediction performance in immunotherapy datasets.Conclusion This study promotes the underlying mechanisms of miRNA-based genes in STAD and offers directions for classification. A five-gene signature accurately predicts the prognosis and helps therapeutic options.

Stomach adenocarcinoma competing endogenous RNA MicroRNA classification prognosis immunotherapy

SCI

英语

其他

The 2021 Key Research and development and transformation plan of Qinghai Provincial Science and Technology Department[2021-SF-148] ; The 2021 Shenyang Science and Technology Plan[2021-34]

Biochemistry & Molecular Biology ; Pharmacology & Pharmacy

Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Pharmacology & Pharmacy

WOS:001209334600007

BENTHAM SCIENCE PUBL LTD

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Jilin Univ, Dept Radiol, China Japan Union Hosp, Changchun 13000, Peoples R China
2.Southern Univ Sci & Technol, Yantian Peoples Hosp, Dept Clin Lab, Shenzhen 518083, Peoples R China
3.Northern Theater Command Gen Hosp, Dept Oncol, Shenyang 110015, Peoples R China
4.YuceBio Technol Co Ltd, Dept Translat Med, Shenzhen 518035, Peoples R China
5.YuceBio Technol Co Ltd, Shenzhen Engn Ctr Translat Med Precis Canc Immunod, Shenzhen 518035, Peoples R China
6.Peoples Hosp Huzhu Tu Ethn Autonomous Cty, Haidong 810500, Qinghai, Peoples R China

Wang, Tianwei,Chen, Piji,Li, Tingting,et al. A Five-gene Signature based on MicroRNA for Predicting Prognosis and Immunotherapy in Stomach Adenocarcinoma[J]. CURRENT MEDICINAL CHEMISTRY,2024,31(17).

Wang, Tianwei.,Chen, Piji.,Li, Tingting.,Li, Jianong.,Zhao, Dong.,...&Liu, Xuefei.(2024).A Five-gene Signature based on MicroRNA for Predicting Prognosis and Immunotherapy in Stomach Adenocarcinoma.CURRENT MEDICINAL CHEMISTRY,31(17).

Wang, Tianwei,et al."A Five-gene Signature based on MicroRNA for Predicting Prognosis and Immunotherapy in Stomach Adenocarcinoma".CURRENT MEDICINAL CHEMISTRY 31.17(2024).