PD-1, PD-L1 and cAMP immunohistochemical expressions are associated with worse oncological outcome in patients with bladder cancer

Abstract

Purpose In this study, we aimed to identify prognostic factors of cancer mortality in patients who received radical cystectomy and to identify genomic alterations in a sub-cohort of patients with locally advanced (pT3-4) and/or positive lymph nodes bladder cancer (BC). Methods We collected 101 BC samples from 2010 to 2018 who previously received radical cystectomy. Immunohistochemical slides were evaluated for PPAR, cAMP, IMP3, Ki67, CDK4, POU5F1, Cyclin E and MDM2, p65, CD3, CD4, CD8, CD20, CD68, CD163, FOXP3, PD-1 and PD-L1 expression. We calculated a prognostic score (PS) based on the positivity to PD-1, PD-L1 and of cAMP (final score ranging from 0 to 3). DNA of each sample have been used for sequencing by NGS in a sub-cohort of 6 patients with locally advanced (pT3-4) and/or positive lymph nodes BC. Results PD-1 + (HR [hazard ratio] 2.59; p = 0.04), PD-L1+ (HR = 6.46; p < 0.01) and cAMP+ (HR 3.04; p = 0.02) were independent predictors of cancer-specific mortality (CSM). Increase of PS (score = 0 as reference) was associated with CSM, 0.81 (p = 0.80), 4.72 (p = 0.01) and 10.51 (p < 0.0) for PS 1, 2 and 3, respectively. ERBB2 was the gene most frequently mutated. Conclusion BC exhibited heterogenous protein expression and variable genomic features. Identification of expression of PD-1, PD-L1 and cAMP could help in predicting oncological outcomes.

Prognostic significance and immunoinfiltration analysis of genes associated with epithelial-mesenchymal transition and energy metabolism in bladder urothelial carcinoma

“…However, multifactorial Cox analysis indicated that only CSPG4 expression (p = 0.00734), CYP1B1 expression (p = 0.02688), HS3ST3B1 expression (p = 0.04957), and ENO1 expression (p = 0.00281) were associated with OS in patients ( Figure 4D – 4I ). Given the high expression of PD1/PD-L1 in BLCA and its significance as a prognostic biomarker, it serves as a crucial target in BLCA immunotherapy [ 32 , 33 ]. Therefore, the study of key genes linked to PD1/PD-L1 assumes substantial importance in the context of BLCA immunotherapy and patient prognosis.…”

Upregulation of CHAC1 promotes bladder inflammation and predicts adverse prognosis in Bladder Urothelial Carcinoma

“…Jin Y et al also revealed an important correlation between CHAC1 expression and the levels of PD-1 and PD-L1 [38]. Recent studies on BLCA have shown that high expression of PD-1 and PD-L1 suggests a worse prognosis [39]. Meanwhile, several in vivo experiments have shown that PD-1 inhibition leads to tumor rejection in mice, while PD-L1 overexpression leads to tumor colonization and disease progression [40,41].…”

Tumor microenvironment and epithelial-mesenchymal transition in bladder cancer: Cytokines in the game?

“…Overall T cells (CD3 + ) were significant increase in MIBC tumors, comparing with high-grade NMIBCs, although no differences were found in bladder peritumoral areas ( Viveiros et al, 2022 ). It was shown that CD3 + in tumor infiltrating lymphocytes (TILs) were related with poor outcome in BlCa patients ( Russo et al, 2022 ). However, Viveiros N et al proved that an enrichment of CD3 + cells, in the intratumoral area, significantly associated with higher disease-free survival (DFS) ( Viveiros et al, 2022 ) and Sjödahl G et al showed that infiltrating CD3 + cells were significantly associated with good prognosis in the MIBC cases ( Sjödahl et al, 2014 ).…”