Research Paper Volume 12, Issue 12 pp 11967—11989

Establishment of a novel risk score model by comprehensively analyzing the immunogen database of bladder cancer to indicate clinical significance and predict prognosis

Lingyun Liu1, *, , Jinghai Hu2, *, , Yu Wang3, , Tao Sun3, , Xiang Zhou4, , Xinyuan Li4, , Fuzhe Ma3, ,

  • 1 Department of Andrology, The First Hospital of Jilin University, Jilin, China
  • 2 Department of Urology, The First Hospital of Jilin University, Jilin, China
  • 3 Department of Nephrology, The First Hospital of Jilin University, Jilin, China
  • 4 Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
* Equal contribution

Received: January 5, 2020       Accepted: May 1, 2020       Published: June 22, 2020
How to Cite

Copyright © 2020 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: Bladder cancer (BCa) has the highest incidence of aggressive malignant tumors in the urogenital system and is the ninth most common cancer worldwide. Immune function-related genes (IFRGs), which are plentiful in immune cells and the immune microenvironment (IME), have the potential to assess prognosis and predict the efficacy of immunotherapy. A complete and significant immunogenomic analysis based on abundant BCa genetic samples from The Cancer Genome Atlas (TCGA) will provide insight into the field.

Results: A total of 57 differentially expressed IFRGs were significantly associated with the clinical outcomes of patients with BCa. Functional enrichment analysis showed that these genes actively participated in the KEGG pathway of human cytomegalovirus infection. Based on the IFRGs (CALR, MMP9, PAEP, RBP7, STAT1, CACYBP, ANHAK, RAC3, SLIT2, EDNRA, IGF1, NAMPT, NTF3, PPY, ADRB2 and SH3BP2), the risk scores were calculated to predict survival and reveal the relationships with age, sex, grade, staging, T-stage, N-stage, and M-stage. Interestingly, IFRG-based risk scores (IRRSs) reflected the infiltration of several types of immune cells. The expression of CACYBP was more significant in grade 3, T3 and T4 stages than in earlier grades and T-stages.

Conclusion: Our results highlighted some sIFRGs with remarkable clinical relevance, showed the driving factors of the immune repertoire, and illustrated the significance of IFRG-based individual immune features in the identification, monitoring, and prognosis of patients with BCa.

Methods: Based on the TCGA dataset, we integrated the expression profiles of IFRGs and overall survival (OS) in 430 patients with BCa. Differentially expressed IFRGs and survival-related IFRGs (sIFRGs) were highlighted by calculating the difference algorithm and COX regression analysis in patients with BCa. Based on computational biology, the potential molecular mechanisms and characteristics of these IFRGs were also explored. Using multivariate Cox analysis, new risk scores based on immune-related genes were developed. The expression of CACYBP was verified by qPCR, western blot and immunohistochemistry. The relations between CACYBP and clinical features were proven by immunohistochemistry.


BCG: bacillus Calmette–Guérin (BCG); BCa: Bladder cancer (BCa); CAR-T: chimeric antigen receptor T-cell (CAR-T); FBS: fetal bovine serum; IRRS: IFRG-based risk scores (IRRS); IFRGs: Immune function-related genes (IFRGs); IME: immune microenvironment (IME); MIBC: muscle invasive cancer (MIBC); NMIBC: non-muscle invasive bladder cancer (NMIBC); OS: overall survival (OS); PD-1: programmed death-1; PD-L1: programmed death-ligand 1; sIFRGs: survival-related IFRGs (sIFRGs); TCGA: The Cancer Genome Atlas (TCGA); TME: tumor microenvironment (TME).