Prognosis and immune infiltration analysis of endoplasmic reticulum stress-related genes in bladder urothelial carcinoma

Yaxuan Wang; Haixia Zhu; Xiaolin Wang

doi:10.3389/fgene.2022.965100

Prognosis and immune infiltration analysis of endoplasmic reticulum stress-related genes in bladder urothelial carcinoma

Front Genet. 2022 Sep 15:13:965100. doi: 10.3389/fgene.2022.965100. eCollection 2022.

Authors

Yaxuan Wang¹, Haixia Zhu², Xiaolin Wang³

Affiliations

¹ Department of Medical School, Nantong University, Nantong, China.
² Department of Central Laboratory, Affiliated Tumor Hospital of Nantong University & Nantong Tumor Hospital, Nantong, China.
³ Department of Urology, Affiliated Tumor Hospital of Nantong University & Nantong Tumor Hospital, Nantong, China.

Abstract

Background: Abnormal activation of endoplasmic reticulum (ER) stress sensors and their downstream signalling pathways is a key regulator of tumour growth, tumour metastasis and the response to chemotherapy, targeted therapy and immunotherapy. However, the study of ER stress on the immune microenvironment of bladder urothelial carcinoma (BLCA) is still insufficient. Methods: Firstly, 23 ER stress genes were selected to analyse their expression differences and prognostic value in BLCA based on the existing BLCA genome atlas data. According to the expression level of ER stress-related genes in BLCA, two independent clusters were identified using consensus cluster analysis. Subsequently, the correlation between these two clusters in terms of the immune microenvironment and their prognostic value was analysed. Finally, we analysed the prognostic value of the key ER stress gene HSP90B1 in BLCA and its corresponding mechanism that affects the immune microenvironment. Results: Consensus clustering showed a worse prognosis and higher expression of immunoassay site-related genes (HAVCR2, PDCD1, CTLA4, CD274, LAG3, TIGIT and PDCD1LG2) in cluster 1 compared with cluster 2. Additionally, both TIMER and CIBERSORT algorithms showed that the expression of immune infiltrating cells in cluster 1 was significantly higher than that in cluster 2. Subsequently, HSP90B1 was identified as a key ER stress gene in BLCA, and its high expression indicated poor prognosis and was closely related to PD1. We also analysed the correlation between HSP90B1 expression and immune-infiltrating cell related biomarkers, which showed positive results. Finally, we verified the prognostic value of HSP90B1 in BLCA using an immunohistochemical assay in a tissue microarray of 100 patients with BLCA, validating the potential of HSP90B1 as a prognostic biomarker in patients with BLCA. Conclusion: Our work reveals that ER stress genes play a crucial role in the BLCA immunological milieu, and HSP90B1 is a potential prognostic biomarker and therapeutic target for cancer immunotherapy.

Keywords: BLCA; ER stress; HSP90B1; immune infiltration; therapeutic target.