Urology Section, Department of Surgery, University of Catania, 95123, Catania, Italy.
Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95123, Catania, Italy.
J Cancer Res Clin Oncol. 2023 Jul;149(7):3681-3690. doi: 10.1007/s00432-022-04262-0. Epub 2022 Aug 16.
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).
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.
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.
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.
本研究旨在确定接受根治性膀胱切除术的患者的癌症死亡率的预后因素，并确定局部晚期（pT3-4）和/或淋巴结阳性膀胱癌（BC）患者亚组的基因组改变。
我们收集了 2010 年至 2018 年期间接受根治性膀胱切除术的 101 例 BC 样本。对免疫组织化学切片进行评估，以确定 PPAR、cAMP、IMP3、Ki67、CDK4、POU5F1、Cyclin E 和 MDM2、p65、CD3、CD4、CD8、CD20、CD68、CD163、FOXP3、PD-1 和 PD-L1 的表达。我们根据 PD-1、PD-L1 和 cAMP 的阳性率（最终评分范围为 0 至 3）计算了预后评分（PS）。在局部晚期（pT3-4）和/或淋巴结阳性 BC 的 6 例患者的亚组中，使用每个样本的 DNA 通过 NGS 进行测序。
PD-1（危险比 [HR] 2.59；p=0.04）、PD-L1（HR=6.46；p<0.01）和 cAMP（HR 3.04；p=0.02）是癌症特异性死亡率（CSM）的独立预测因素。PS 增加（评分=0 作为参考）与 CSM 相关，PS 为 1、2 和 3 时分别为 0.81（p=0.80）、4.72（p=0.01）和 10.51（p<0.0）。最常发生突变的基因是 ERBB2。
BC 表现出异质性的蛋白表达和不同的基因组特征。PD-1、PD-L1 和 cAMP 的表达鉴定有助于预测肿瘤学结果。
