Effect of unfolded protein response on the immune infiltration and prognosis of transitional cell bladder cancer

Background: Bladder cancer (BC) is one of the most common human malignancies worldwide. Previous researches have shown that the unfolded protein response (UPR) pathway could contribute to the tumorigenesis of BC. However, the role of UPR in the immune infiltration, progression, and prognosis of BC is unclear. Methods: The GSVA and ssGSEA methods were used for assessing the UPR score and immune cells infiltration score in three BC public datasets, respectively. The relationship between the UPR pathway and clinicopathological characteristics was analyzed by the Kruskal-Wallis, Wilcox test, and log-rank test. The association of the UPR pathway with various tumor-infiltrating immune cells was evaluated with the correlation analysis. Univariate Cox regression analysis was performed to identify risk factors significantly associated with prognosis. The predictive models were built based on risk factors and visualized with nomograms. The performance of our models was evaluated with the calibration curve, Harrell's concordance index (c-index), and receiver operating characteristic (ROC) analysis. Results: We found that the UPR pathway and many UPR-related genes were significantly associated with the pathologic grade, tumor type, and invasive progression of transitional cell bladder cancer (TCBC), and a high UPR score predicted a poor prognosis in patients. The UPR score was positively correlated with the infiltration abundance of many tumor immune cells in TCBC. Besides, we constructed predictive models based on the UPR score, and good performance was observed, with c-indexes ranging from 0.74 to 0.87. Conclusions: Our study proved that the UPR pathway may have an important impact on the progression, prognosis, and tumor immune infiltration in TCBC, and the models we built may provide effective and reliable guides for prognosis assessment and treatment decision-making for TCBC patients.