Immune-Related Genes Are Prognostic Markers for Prostate Cancer Recurrence

Min Fu; Qiang Wang; Hanbo Wang; Yun Dai; Jin Wang; Weiting Kang; Zilian Cui; Xunbo Jin

doi:10.3389/fgene.2021.639642

Immune-Related Genes Are Prognostic Markers for Prostate Cancer Recurrence

Front Genet. 2021 Aug 19:12:639642. doi: 10.3389/fgene.2021.639642. eCollection 2021.

Authors

Min Fu^{1

2}, Qiang Wang³, Hanbo Wang^{1

3}, Yun Dai^{4

5}, Jin Wang^{6

7}, Weiting Kang^{1

2}, Zilian Cui^{1

2}, Xunbo Jin^{1

2}

Affiliations

¹ Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
² Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
³ Department of Human Resources, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁴ Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁵ Department of Ultrasound, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁶ Department of Urology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
⁷ Department of Urology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Abstract

Background: Prostate cancer (PCa) is an immune-responsive disease. The current study sought to explore a robust immune-related prognostic gene signature for PCa.

Methods: Data were retrieved from the tumor Genome Atlas (TCGA) database and GSE46602 database for performing the least absolute shrinkage and selection operator (LASSO) cox regression model analysis. Immune related genes (IRGs) data were retrieved from ImmPort database.

Results: The weighted gene co-expression network analysis (WGCNA) showed that nine functional modules are correlated with the biochemical recurrence of PCa, including 259 IRGs. Univariate regression analysis and survival analysis identified 35 IRGs correlated with the prognosis of PCa. LASSO Cox regression model analysis was used to construct a risk prognosis model comprising 18 IRGs. Multivariate regression analysis showed that risk score was an independent predictor of the prognosis of PCa. A nomogram comprising a combination of this model and other clinical features showed good prediction accuracy in predicting the prognosis of PCa. Further analysis showed that different risk groups harbored different gene mutations, differential transcriptome expression and different immune infiltration levels. Patients in the high-risk group exhibited more gene mutations compared with those in the low-risk group. Patients in the high-risk groups showed high-frequency mutations in TP53. Immune infiltration analysis showed that M2 macrophages were significantly enriched in the high-risk group implying that it affected prognosis of PCa patients. In addition, immunostimulatory genes were differentially expressed in the high-risk group compared with the low-risk group. BIRC5, as an immune-related gene in the prediction model, was up-regulated in 87.5% of prostate cancer tissues. Knockdown of BIRC5 can inhibit cell proliferation and migration.

Conclusion: In summary, a risk prognosis model based on IGRs was developed. A nomogram comprising a combination of this model and other clinical features showed good accuracy in predicting the prognosis of PCa. This model provides a basis for personalized treatment of PCa and can help clinicians in making effective treatment decisions.

Keywords: LASSO Cox regression; immune infiltration; immune-related genes; nomogram; prostate cancer; weighted gene co-expression network analysis.