Data documento
19/03/2025

Título
Immune-checkpoint gene expression and BCG response in non-muscle invasive bladder cancer

Autor(es)
Zucca LER, Laus AC - Sorroche BP - Paro E Sussuchi L - Marques RF - Teixeira GR - Berardinelli GN - Arantes LMRB - Reis RM - Cárcano FM.

Palavras chave
Urinary bladder neoplasms1 - BCG vaccine 2 - Gene expression profiling3 - Immunity active4

Resumo
Methods One-hundred-six patients diagnosed with non-muscle invasive bladder cancer and treated with intravesical BCG were included and divided into two groups, BCG-responsive (n = 47) and -unresponsive (n = 59). Immunohistochemistry was used to evaluate PD-L1 expression and MSI was assessed by a commercial multiplex PCR kit. The mRNA expression profile of 15 immune checkpoints was performed using the nCounter technology. For in silico validation, two distinct cohorts sourced from the Gene Expression Omnibus (GEO) database were used. Results Among the 106 patients, only one (<1 %) exhibited MSI instability. PD-L1 expression was present in 9.4 % of cases, and no association was found with BCG-responsive status. We found low gene expression of canonic actionable immune checkpoints PDCD1 (PD-1), CD274 (PD-L1), and CTLA4, while high expression was observed for CD276 (B7-H3), CD47, TNFRSF14, IDO1 and PVR (CD155) genes. High IDO1 expression levels was associated with worst overall survival. The PDCD1, CTLA4 and TNFRSF14 expression levels were associated with BCG responsiveness, whereas TIGIT and CD276 were associated with unresponsiveness. Finally, CD276 was validated in silico cohorts. Conclusion In NMIBC, MSI is rare and PD-L1 expression is present in a small subset of cases. Expression levels of PDCD1, CTLA4, TNFRSF14, TIGIT and CD276 could constitute predictive biomarkers of BCG responsiveness.

Citação
Zucca LER, Laus AC, Sorroche BP, Paro E, Sussuchi L, Marques RF, Teixeira GR, Berardinelli GN, Arantes LMRB, Reis RM, Cárcano FM. Transl Oncol. 2024 Aug;46:102003. doi: 10.1016/j.tranon.2024.102003. Epub 2024 Jun 4. PMID: 38838438

Data documento
03/05/2024

Título
Somatic mutation detection and KRAS amplification in testicular germ cell tumors

Autor(es)
Cabral ERM, - Pacanhella MF, - Lengert AVH, - Dos Reis MB, - Leal LF, - de Lima MA, - da Silva ALV, - Pinto IA, - Reis RM, - Pinto MT, - Cárcano FM.

Palavras chave
K-ras Gene - TP53 Gene - mutation - next-generation sequencing - testicular germ cell tumor - testicular neoplasms

Resumo
Background: Testicular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of KRAS in a large series of TGCT from a single reference cancer center. Materials and methods: A cohort of 97 patients with TGCT, diagnosed at the Barretos Cancer Hospital, was evaluated. Real-time PCR was used to assess copy number variation (CNV) of the KRAS gene in 51 cases, and the mutation analysis was performed using the TruSight Tumor 15 (Illumina) panel (TST15) in 65 patients. Univariate analysis was used to compare sample categories in relation to mutational frequencies. Survival analysis was conducted by the Kaplan-Meier method and log-rank test. Results: KRAS copy number gain was a very frequent event (80.4%) in TGCT and presented a worse prognosis compared with the group with no KRAS copy gain (10y-OS, 90% vs. 81.5%, p = 0.048). Among the 65 TGCT cases, different variants were identified in 11 of 15 genes of the panel, and the TP53 gene was the most recurrently mutated driver gene (27.7%). Variants were also detected in genes such as KIT, KRAS, PDGFRA, EGFR, BRAF, RET, NRAS, PIK3CA, MET, and ERBB2, with some of them potentially targetable. Conclusion: Although larger studies incorporating collaborative networks may shed the light on the molecular landscape of TGCT, our findings unveal the potential of actionable variants in clinical management for applying targeted therapies.

Citação
Cabral ERM, Pacanhella MF, Lengert AVH, Dos Reis MB, Leal LF, de Lima MA, da Silva ALV, Pinto IA, Reis RM, Pinto MT, Cárcano FM. Somatic mutation detection and KRAS amplification in testicular germ cell tumors. Front Oncol. 2023 Mar 16;13:1133363. doi: 10.3389/fonc.2023.1133363. PMID: 37007070; PMCID: PMC10060882.