Abstract
Tremendous progress has been made in development of immunotherapeutic approaches for treatment of bladder urothelial carcinoma (BLCA). However, efficacy and safety of these approaches remain unsatisfactory, necessitating further investigations for identification of indicators for predicting prognosis and efficacy. In this study, we downloaded transcriptomic and clinical data of BLCA patients from The Cancer Genome Atlas (TCGA) database, and identified differentially expressed genes (DEGs) between tumor and normal tissues. We incorporated these DEGs in an intersection analysis with immune-related genes (IRGs) obtained from the Immunology Database and Analysis Portal (ImmPort) database, and identified immune-related DEGs. These genes were subjected to Cox and least absolute shrinkage and selection operator (LASSO) regression analyses, then a prognostic model containing AHNAK, OAS1, NGF, PPY and SCG2 genes was constructed, for prediction of prognosis of BLCA and efficacy of immunotherapy. Finally, we explored the relationship between the prognostic model and tumor mutational burden (TMB), abundance of tumor-infiltrating immune cells (TICs) and immunotherapeutic targets, and found that patients with higher risk score (RS) had poorer prognosis and significantly lower levels of TMB. Patients in the low-RS group exhibited higher numbers of lymphoid cells, whereas those in the high-RS group exhibited higher proportions of myeloid cells. However, patients with high-RS tended to respond better to immunotherapy relative to those in the low-RS group. The constructed prognostic model provides a new tool for predicting prognosis of BLCA patients and efficacy of immunotherapy, offering a feasible option for management of the disease.
Highlights
Bladder urothelial carcinoma (BLCA) is a common malignancy that negatively affects human health
The rapid advancement in immunotherapy in recent years has generated a variety of immune checkpoint inhibitors (ICIs) which have been applied for treatment of bladder urothelial carcinoma (BLCA) since 2016 (Özdemir et al, 2018)
Screening for differentially expressed genes (DEGs), based on |log2FC|>1 and false discovery rate (FDR)
Summary
Bladder urothelial carcinoma (BLCA) is a common malignancy that negatively affects human health. Incidence of tumor recurrence after TURBT reportedly ranges from 50 to 70%, with 30% of the patients progressing to muscle-invasive bladder cancer (MIBC) (Kamat et al, 2016). This highly malignant condition, which is characterized by a high rate of postoperative distant metastasis, negatively affects patients’ life quality (Flaig et al, 2020). A phase II clinical trial, comprising 310 patients with locally advanced and metastatic BLCA, found that TMB was associated with patients prognosis and could predict treatment responses of atezolizumab (Rosenberg et al, 2016). The relationship between TMB and immune response in bladder cancer is still unclear
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