Database Mining of Genes of Prognostic Value for the Prostate Adenocarcinoma Microenvironment Using the Cancer Gene Atlas

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2020 Jun 9

PMID 32509861

Citations 22

Authors

Xin Zhao

Daixing Hu

Jia Li

Guozhi Zhao

Wei Tang

Honglin Cheng

Affiliations

Soon will be listed here.

Abstract

Background: Prostate adenocarcinoma (PRAD) is a common malignant tumor in elderly men. Our research uses The Cancer Gene Atlas (TCGA) database to find potential related genes for predicting the prognosis of patients with PRAD.

Methods: We downloaded gene expression profiles and clinical sample information from TCGA for 490 patients with PRAD (patient age: 41-78 years). We calculated stromal and immune scores using the ESTIMATE algorithm to predict the level of stromal and immune cell infiltration. We categorized patients with PRAD in TCGA into high and low score arrays according to their median immune/stromal scores and identified differentially expressed genes (DEGs) that were significantly correlated with the prognosis of PRAD. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. The association between DEGs and overall survival was investigated by weighted Kaplan-Meier survival analysis and multivariate analysis. Furthermore, the protein-protein interaction network (PPI) of DEGs was constructed using the STRING tool. Finally, the hub genes were identified by analyzing the degree of association of PPI networks.

Results: We found that 8 individual DEGs, C6, S100A12, MLC1, PAX5, C7, FAM162B, CAMK1G, and TCEAL5, were significantly predictive of favorable overall survival and one DEG, EPYC, was associated with poor overall survival. GO and KEGG pathway analyses revealed that the DEGs were associated with immune responses. Moreover, 30 hub genes were obtained using the PPI network of DEGs: ITGAM, CD4, CD3E, IL-10, LCP2, ITGB2, ZAP-70, C3, CCL19, CXCL13, CXCL9, BTK, CCL21, CD247, CD28, CD3D, FCER1G, PTPRC, TYROBP, CCR5, ITK, CCL13, CCR1, CCR2, CD79B, CYBB, IL2RG, JAK3, PLCG2, and CD19. These prominent nodes had the most associations with other genes, indicating that they might play crucial roles in the prognosis of PRAD.

Conclusions: We extracted a list of genes associated with the prostate adenocarcinoma microenvironment, which might contribute to the prediction and interpretation of PRAD prognosis.

Citing Articles

Role of arachidonic acid metabolism in osteosarcoma prognosis by integrating WGCNA and bioinformatics analysis.

Wang Y, Hsu P, Hu H, Lin F, Wei X BMC Cancer. 2025; 25(1):445.

PMID: 40075313 PMC: 11905593. DOI: 10.1186/s12885-024-13278-3.

Li S, Zhang L, Zhang H Front Pharmacol. 2025; 15:1532610.

PMID: 39980969 PMC: 11841432. DOI: 10.3389/fphar.2024.1532610.

Evidence of the Link between Stroma Remodeling and Prostate Cancer Prognosis.

Vecchiotti D, Clementi L, Cornacchia E, Di Vito Nolfi M, Verzella D, Capece D Cancers (Basel). 2024; 16(18).

PMID: 39335188 PMC: 11430343. DOI: 10.3390/cancers16183215.

PLCG2, A Regulator of Lung Adenocarcinoma Proliferation and Migration Associated with Immune Infiltration.

Chen S, Zhou C, Dai J, Xu Q, Chen Y, Hu Z Curr Cancer Drug Targets. 2024; 25(2):159-169.

PMID: 39177130 DOI: 10.2174/0115680096307100240801095132.

Change in prostate tissue gene expression following finasteride or doxazosin administration in the medical therapy for prostatic symptoms (MTOPS) study.

Choi H, Torkko K, Lucia M, Mozhui K, Choi W, Clark P Sci Rep. 2024; 14(1):19164.

PMID: 39160179 PMC: 11333712. DOI: 10.1038/s41598-024-69301-x.

References

Comito G, Iscaro A, Bacci M, Morandi A, Ippolito L, Parri M . Lactate modulates CD4 T-cell polarization and induces an immunosuppressive environment, which sustains prostate carcinoma progression via TLR8/miR21 axis. Oncogene. 2019; 38(19):3681-3695. DOI: 10.1038/s41388-019-0688-7. View

Garg R, Blando J, Perez C, Abba M, Benavides F, Kazanietz M . Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway. Cell Rep. 2017; 19(2):375-388. PMC: 5444089. DOI: 10.1016/j.celrep.2017.03.042. View

Grignon D . Unusual subtypes of prostate cancer. Mod Pathol. 2004; 17(3):316-27. DOI: 10.1038/modpathol.3800052. View

Wang Q, Hu B, Hu X, Kim H, Squatrito M, Scarpace L . Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment. Cancer Cell. 2017; 32(1):42-56.e6. PMC: 5599156. DOI: 10.1016/j.ccell.2017.06.003. View

Sia M, Rosewall T, Warde T . Radiotherapy as primary treatment modality. Front Radiat Ther Oncol. 2008; 41:15-25. DOI: 10.1159/000139874. View

Kawasaki K, Kondoh E, Chigusa Y, Kawamura Y, Mogami H, Takeda S . Metabolomic Profiles of Placenta in Preeclampsia. Hypertension. 2019; 73(3):671-679. DOI: 10.1161/HYPERTENSIONAHA.118.12389. View

Wong P, AbuBakar S . High intracellular Zn2+ ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells. Cell Mol Biol Lett. 2008; 13(3):375-90. PMC: 6276015. DOI: 10.2478/s11658-008-0009-6. View

Jang Y, Go R, Hwang K, Choi K . Resveratrol inhibits DHT-induced progression of prostate cancer cell line through interfering with the AR and CXCR4 pathway. J Steroid Biochem Mol Biol. 2019; 192:105406. DOI: 10.1016/j.jsbmb.2019.105406. View

Elmasry M, Brandl L, Engel J, Jung A, Kirchner T, Horst D . RBP7 is a clinically prognostic biomarker and linked to tumor invasion and EMT in colon cancer. J Cancer. 2019; 10(20):4883-4891. PMC: 6775517. DOI: 10.7150/jca.35180. View

10.

Szklarczyk D, Morris J, Cook H, Kuhn M, Wyder S, Simonovic M . The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2016; 45(D1):D362-D368. PMC: 5210637. DOI: 10.1093/nar/gkw937. View

11.

Yoshihara K, Shahmoradgoli M, Martinez E, Vegesna R, Kim H, Torres-Garcia W . Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013; 4:2612. PMC: 3826632. DOI: 10.1038/ncomms3612. View

12.

Fuchsova R, Topolcan O, Windrichova J, Hora M, Dolejsova O, Pecen L . PHI in the Early Detection of Prostate Cancer. Anticancer Res. 2015; 35(9):4855-7. View

13.

Sun M, Wu D, Zhou K, Li H, Gong X, Wei Q . An eight-lncRNA signature predicts survival of breast cancer patients: a comprehensive study based on weighted gene co-expression network analysis and competing endogenous RNA network. Breast Cancer Res Treat. 2019; 175(1):59-75. DOI: 10.1007/s10549-019-05147-6. View

14.

Johnson M, Franks J, Cai G, Mehta B, Wood T, Archambault K . Microbiome dysbiosis is associated with disease duration and increased inflammatory gene expression in systemic sclerosis skin. Arthritis Res Ther. 2019; 21(1):49. PMC: 6366065. DOI: 10.1186/s13075-019-1816-z. View

15.

Mao T, Fan K, Liu C . Targeting the CXCR4/CXCL12 axis in treating epithelial ovarian cancer. Gene Ther. 2017; 24(10):621-629. DOI: 10.1038/gt.2017.69. View

16.

Chung S, Wu Y, Okobi Q, Adekoya D, Atefi M, Clarke O . Proinflammatory Cytokines IL-6 and TNF- Increased Telomerase Activity through NF-B/STAT1/STAT3 Activation, and Withaferin A Inhibited the Signaling in Colorectal Cancer Cells. Mediators Inflamm. 2017; 2017:5958429. PMC: 5476880. DOI: 10.1155/2017/5958429. View

17.

Kumar S, Singh R, Malik S, Manne U, Mishra M . Prostate cancer health disparities: An immuno-biological perspective. Cancer Lett. 2017; 414:153-165. PMC: 5743619. DOI: 10.1016/j.canlet.2017.11.011. View

18.

Yin B, Liu W, Yu P, Liu C, Chen Y, Duan X . Association between human papillomavirus and prostate cancer: A meta-analysis. Oncol Lett. 2017; 14(2):1855-1865. PMC: 5529902. DOI: 10.3892/ol.2017.6367. View

19.

Aldape K, Zadeh G, Mansouri S, Reifenberger G, von Deimling A . Glioblastoma: pathology, molecular mechanisms and markers. Acta Neuropathol. 2015; 129(6):829-48. DOI: 10.1007/s00401-015-1432-1. View

20.

Ni J, Wu Y, Qi F, Li X, Yu S, Liu S . Screening the Cancer Genome Atlas Database for Genes of Prognostic Value in Acute Myeloid Leukemia. Front Oncol. 2020; 9:1509. PMC: 6990132. DOI: 10.3389/fonc.2019.01509. View