A Prognostic Model for Predicting Tumor Mutation Burden and Tumor-Infiltrating Immune Cells in Bladder Urothelial Carcinoma

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.

Investigating cellular similarities and differences between upper tract urothelial carcinoma and bladder urothelial carcinoma using single-cell sequencing

“…Tumor-infiltrating T lymphocytes (TILs) represent a heterogeneous cell subpopulation within the TME ( 12 , 25 ). They exhibit significant plasticity and are associated with patient survival and therapeutic response in UC, making them a critical focus for distinguishing UTUC and BLCA.…”

Preliminary exploration of the potential biological functions and prognosis values of RAB4B in pan-cancer combing with experimental validation in BLCA

“…TMB, the total number of mutations in each coding region of the tumor genome, can be used to predict ICI efficacy ( 28 ). Interestingly, a significantly longer survival period was observed in the high-TMB group in comparison with the low-TMB group, suggesting that TMB is related to the prognosis of BLCA, and it has emerged as a useful biomarker for multiple cancer types to identify patients who may benefit from immunotherapy ( 29 , 30 ). On the other hand, a study has shown that MSI, independent of tumor histology and completely dependent on tumor gene composition, is a pan-cancer biomarker for predicting immunotherapy response ( 31 ).…”

An epithelial–mesenchymal transition-related mRNA signature associated with the prognosis, immune infiltration and therapeutic response of colon adenocarcinoma

“…However, PCOLCE2 remains to be validated in vivo and in vitro for its specific mechanism in the EMT process of COAD. SCG2 has been identified as a prognostic biomarker associated with immune infiltration in CRC (41,42), bladder cancer (43,44), breast cancer (45), and lung adenocarcinoma (46). Wet assays revealed that SCG2 is lowly expressed in CRC, and inhibits the growth and angiogenesis of CRC cells by promoting the degradation of HIF-1α (47).…”