Immune-related Gene Signature Predicts Overall Survival of Gastric Cancer Patients with Varying Microsatellite Instability Status

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2020 Dec 14

PMID 33316777

Citations 10

Authors

Ruyue Tian

Jiexuan Hu

Xiao Ma

Lei Liang

Shuilong Guo

Affiliations

Soon will be listed here.

Abstract

Purpose: Gastric cancer (GC) is one of the most common and fatal malignancies globally. While microsatellite instability (MSI) index has earlier been correlated with survival outcome in gastric cancer patients, the present study aims to construct a risk-stratification model based on immune-related genes in GC patients with varying MSI status.

Results: The univariate and multivariate Cox regression analyses identified SEMA7A, NUDT6, SCGB3A1, NPR3, PTH1R, and SHC4 as signature genes, which were used to build the prognostic model for GC patients with microsatellite instability-low (MSI-L) and microsatellite stable (MSS). Whereas, for GC patients with microsatellite instability-high (MSI-H), prognostic model was established with three genes (SEMA6A, LTBP1, and BACH2), based on the univariate and multivariate Cox regression, and Kaplan-Meier survival analyses.

Conclusion: The prognostic immune-related gene signature identified in this study may offer new targets for personalized treatment and immunotherapy for GC patients with MSI-H or MSI-L/MSS status.

Methods: The Cancer Genome Atlas (TCGA) and ImmPort databases were used to extract expression data and to explore prognostic genes from the immune-related genes (IRGs), respectively. Univariate and multivariate Cox regression analysis were applied to identify IRGs correlated with patient prognosis. The regulatory network between prognostic IRGs and TFs were performed using R software.

Citing Articles

Transcriptome-Based Survival Analysis Identifies as a Prognostic Marker in Gastric Cancer with Microsatellite Instability.

Huamani Ortiz A, Campos Segura A, Magano Bocanegra K, Velasquez Sotomayor M, Barron Pastor H, Llimpe Mitma de Barron Y Cancers (Basel). 2025; 17(3).

PMID: 39941781 PMC: 11816344. DOI: 10.3390/cancers17030412.

Associations of SEMA7A, SEMA4D, ADAMTS10, and ADAM8 with KRAS, NRAS, BRAF, PIK3CA, and AKT Gene Mutations, Microsatellite Instability Status, and Cytokine Expression in Colorectal Cancer Tissue.

Ochman B, Limanowka P, Mielcarska S, Kula A, Dawidowicz M, Wagner W Curr Issues Mol Biol. 2024; 46(9):10218-10248.

PMID: 39329961 PMC: 11431007. DOI: 10.3390/cimb46090609.

Development and verification of a manganese metabolism- and immune-related genes signature for prediction of prognosis and immune landscape in gastric cancer.

Han X, Leng C, Zhao S, Wang S, Chen S, Wang S Front Immunol. 2024; 15:1377472.

PMID: 38807601 PMC: 11131102. DOI: 10.3389/fimmu.2024.1377472.

Semaphorin 6 Family-An Important Yet Overlooked Group of Signaling Proteins Involved in Cancerogenesis.

Wagner W, Ochman B, Wagner W Cancers (Basel). 2023; 15(23).

PMID: 38067240 PMC: 10705753. DOI: 10.3390/cancers15235536.

Osteosarcoma-Associated Immune Genes as Potential Immunotherapy and Prognosis Biomarkers.

Yang L, Long Y, Xiao S Biochem Genet. 2023; 62(2):798-813.

PMID: 37452172 DOI: 10.1007/s10528-023-10444-3.

References

Aoyama T, Yoshikawa T, Watanabe T, Hayashi T, Ogata T, Cho H . Survival and prognosticators of gastric cancer that recurs after adjuvant chemotherapy with S-1. Gastric Cancer. 2011; 14(2):150-4. DOI: 10.1007/s10120-011-0020-x. View

Ratti M, Lampis A, Hahne J, Passalacqua R, Valeri N . Microsatellite instability in gastric cancer: molecular bases, clinical perspectives, and new treatment approaches. Cell Mol Life Sci. 2018; 75(22):4151-4162. PMC: 6182336. DOI: 10.1007/s00018-018-2906-9. View

Cristescu R, Lee J, Nebozhyn M, Kim K, Ting J, Wong S . Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015; 21(5):449-56. DOI: 10.1038/nm.3850. View

Fang W, Chang S, Lan Y, Huang K, Chen J, Lo S . Microsatellite instability is associated with a better prognosis for gastric cancer patients after curative surgery. World J Surg. 2012; 36(9):2131-8. DOI: 10.1007/s00268-012-1652-7. View

Ichikawa S, Fukuhara N, Katsushima H, Takahashi T, Yamamoto J, Yokoyama H . Association between BACH2 expression and clinical prognosis in diffuse large B-cell lymphoma. Cancer Sci. 2014; 105(4):437-44. PMC: 4317811. DOI: 10.1111/cas.12361. View

Chen X, Yue B, Zhang C, Qi M, Qiu J, Wang Y . inhibits the viability, proliferation, invasion, and cell cycle, and promotes apoptosis of nasopharyngeal carcinoma cells by suppressing BACH2 expression. Biosci Rep. 2017; 37(3). PMC: 5463266. DOI: 10.1042/BSR20160576. View

Sohn B, Hwang J, Jang H, Lee H, Oh S, Shim J . Clinical Significance of Four Molecular Subtypes of Gastric Cancer Identified by The Cancer Genome Atlas Project. Clin Cancer Res. 2017; 23(15):4441-4449. PMC: 5785562. DOI: 10.1158/1078-0432.CCR-16-2211. View

Kim S, Choi Y, An J, Shin H, Jo A, Choi H . The benefit of microsatellite instability is attenuated by chemotherapy in stage II and stage III gastric cancer: Results from a large cohort with subgroup analyses. Int J Cancer. 2015; 137(4):819-25. DOI: 10.1002/ijc.29449. View

Liang H, Zhong Y, Huang Y, Chen G . Type 1 receptor parathyroid hormone (PTH1R) influences breast cancer cell proliferation and apoptosis induced by high levels of glucose. Med Oncol. 2011; 29(2):439-45. DOI: 10.1007/s12032-011-9851-x. View

10.

Cunningham D, Allum W, Stenning S, Thompson J, van de Velde C, Nicolson M . Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006; 355(1):11-20. DOI: 10.1056/NEJMoa055531. View

11.

Torre L, Bray F, Siegel R, Ferlay J, Lortet-Tieulent J, Jemal A . Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2):87-108. DOI: 10.3322/caac.21262. View

12.

Siegel R, Miller K, Jemal A . Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1):7-30. DOI: 10.3322/caac.21387. View

13.

Muro K, Chung H, Shankaran V, Geva R, Catenacci D, Gupta S . Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol. 2016; 17(6):717-726. DOI: 10.1016/S1470-2045(16)00175-3. View

14.

Smyth E, Wotherspoon A, Peckitt C, Gonzalez D, Hulkki-Wilson S, Eltahir Z . Mismatch Repair Deficiency, Microsatellite Instability, and Survival: An Exploratory Analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial. JAMA Oncol. 2017; 3(9):1197-1203. PMC: 5824280. DOI: 10.1001/jamaoncol.2016.6762. View

15.

Gensure R, Gardella T, Juppner H . Parathyroid hormone and parathyroid hormone-related peptide, and their receptors. Biochem Biophys Res Commun. 2005; 328(3):666-78. DOI: 10.1016/j.bbrc.2004.11.069. View

16.

Le D, Uram J, Wang H, Bartlett B, Kemberling H, Eyring A . PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015; 372(26):2509-20. PMC: 4481136. DOI: 10.1056/NEJMoa1500596. View

17.

Roychoudhuri R, Eil R, Clever D, Klebanoff C, Sukumar M, Grant F . The transcription factor BACH2 promotes tumor immunosuppression. J Clin Invest. 2016; 126(2):599-604. PMC: 4731158. DOI: 10.1172/JCI82884. View

18.

Monego G, Lauriola L, Ramella S, Dangelillo R, Lanza P, Granone P . Parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor type 1 expression in human lung adenocarcinoma. Chest. 2009; 137(4):898-908. DOI: 10.1378/chest.09-1358. View

19.

Zhao P, Li L, Jiang X, Li Q . Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J Hematol Oncol. 2019; 12(1):54. PMC: 6544911. DOI: 10.1186/s13045-019-0738-1. View

20.

Zhang H, Chen Z, Miranda R, Medeiros L, McCarty N . Bifurcated BACH2 control coordinates mantle cell lymphoma survival and dispersal during hypoxia. Blood. 2017; 130(6):763-776. PMC: 5553575. DOI: 10.1182/blood-2017-02-767293. View