Identification of Immune-Related Genes Associated With Bladder Cancer Based on Immunological Characteristics and Their Correlation With the Prognosis

Zhen Kang; Wei Li; Yan-Hong Yu; Meng Che; Mao-Lin Yang; Jin-Jun Len; Yue-Rong Wu; Jun-Feng Yang

doi:10.3389/fgene.2021.763590

Identification of Immune-Related Genes Associated With Bladder Cancer Based on Immunological Characteristics and Their Correlation With the Prognosis

Front Genet. 2021 Nov 26:12:763590. doi: 10.3389/fgene.2021.763590. eCollection 2021.

Authors

Zhen Kang^{1

2}, Wei Li^{1

2}, Yan-Hong Yu^{1

2}, Meng Che¹, Mao-Lin Yang^{1

2}, Jin-Jun Len^{1

2}, Yue-Rong Wu¹, Jun-Feng Yang^{1

2}

Affiliations

¹ The Affiliated Hospital, Kunming University of Science and Technology, Kunming, China.
² Department of Urology, The First People's Hospital of Yunnan Province, Kunming, China.

Abstract

Background: To identify the immune-related genes of bladder cancer (BLCA) based on immunological characteristics and explore their correlation with the prognosis.

Methods: We downloaded the gene and clinical data of BLCA from the Cancer Genome Atlas (TCGA) as the training group, and obtained immune-related genes from the Immport database. We downloaded GSE31684 and GSE39281 from the Gene Expression Omnibus (GEO) as the external validation group. R (version 4.0.5) and Perl were used to analyze all data.

Result: Univariate Cox regression analysis and Lasso regression analysis revealed that 9 prognosis-related immunity genes (PIMGs) of differentially expressed immune genes (DEIGs) were significantly associated with the survival of BLCA patients (p < 0.01), of which 5 genes, including NPR2, PDGFRA, VIM, RBP1, RBP1 and TNC, increased the risk of the prognosis, while the rest, including CD3D, GNLY, LCK, and ZAP70, decreased the risk of the prognosis. Then, we used these genes to establish a prognostic model. We drew receiver operator characteristic (ROC) curves in the training group, and estimated the area under the curve (AUC) of 1-, 3- and 5-year survival for this model, which were 0.688, 0.719, and 0.706, respectively. The accuracy of the prognostic model was verified by the calibration chart. Combining clinical factors, we established a nomogram. The ROC curve in the external validation group showed that the nomogram had a good predictive ability for the survival rate, with a high accuracy, and the AUC values of 1-, 3-, and 5-year survival were 0.744, 0.770, and 0.782, respectively. The calibration chart indicated that the nomogram performed similarly with the ideal model.

Conclusion: We had identified nine genes, including PDGFRA, VIM, RBP1, RBP1, TNC, CD3D, GNLY, LCK, and ZAP70, which played important roles in the occurrence and development of BLCA. The prognostic model based on these genes had good accuracy in predicting the OS of patients and might be promising candidates of therapeutic targets. This study may provide a new insight for the diagnosis, treatment and prognosis of BLCA from the perspective of immunology. However, further experimental studies are necessary to reveal the underlying mechanisms by which these genes mediate the progression of BLCA.

Keywords: bladder cancer; immune characteristics; ssGSEA; tumor immunity; urology.