Kumar Nikhil, Singh Mithalesh Kumar, Singh Lata, Lomi Neiwete, Meel Rachna, Pushker Neelam, Sen Seema, Kashyap Seema
Department of Ocular Pathology, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
Department of Ophthalmology, University of California, Irvine, CA, USA.
Hum Cell. 2023 Jan;36(1):342-352. doi: 10.1007/s13577-022-00808-z. Epub 2022 Oct 25.
Existing clinical indicators for metastatic risk classification and patient treatment of uveal melanoma (UM) in the Asian population are limited. Preferentially expressed antigen in melanoma (PRAME) has gained attention in the prognosis of cancers and considered as a potential biomarker in many tumors including UM. Therefore, this study investigated the expression of PRAME and its association with loss of nuclear BAP1 (nBAP1) as well as its correlation with clinicopathological parameters and patient outcome. Immunohistochemical expression of PRAME and BAP1 proteins were assessed in 66 prospective cases of UM. mRNA expression level was measured by quantitative real-time PCR. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the correlation of protein expression with clinicopathological parameters, metastasis-free survival and overall survival. Nuclear PRAME (nPRAME) expression and loss of nBAP1 were observed in 24 and 62% cases, respectively. PRAME mRNA expression level was found to be upregulated in 64% (7/11) of metastatic patients. mRNA and immunoexpression of nPRAME were statistically significant with many clinicopathological high-risk factors. On univariate and multivariate analyses, high mitotic activity, extraocular invasion and presence of nPRAME expression were statistically significant (p < 0.05). On Kaplan-Meier survival analysis, patients expressing PRAME had significantly reduced metastasis-free survival (MFS) and overall survival (OS). MFS and OS were also reduced in patients expressing PRAME along with loss of nBAP1. Our data show that nPRAME expression, in combination with loss of nBAP1, could be a useful predictive biomarker in the therapeutic management of UM patients at high risk.
亚洲人群中用于葡萄膜黑色素瘤（UM）转移风险分类和患者治疗的现有临床指标有限。黑色素瘤优先表达抗原（PRAME）在癌症预后方面受到关注，并被认为是包括UM在内的许多肿瘤的潜在生物标志物。因此，本研究调查了PRAME的表达及其与核BAP1（nBAP1）缺失的关联，以及其与临床病理参数和患者预后的相关性。对66例前瞻性UM病例评估了PRAME和BAP1蛋白的免疫组化表达。通过定量实时PCR测量mRNA表达水平。使用Kaplan-Meier曲线和Cox比例风险模型分析蛋白表达与临床病理参数、无转移生存期和总生存期的相关性。分别在24%和62%的病例中观察到核PRAME（nPRAME）表达和nBAP1缺失。在64%（7/11）的转移患者中发现PRAME mRNA表达水平上调。nPRAME的mRNA和免疫表达与许多临床病理高危因素具有统计学意义。单因素和多因素分析显示，高有丝分裂活性、眼外侵犯和nPRAME表达的存在具有统计学意义（p < 0.05）。在Kaplan-Meier生存分析中，表达PRAME的患者无转移生存期（MFS）和总生存期（OS）显著降低。同时表达PRAME和nBAP1缺失的患者MFS和OS也降低。我们的数据表明，nPRAME表达与nBAP1缺失相结合，可能是UM高危患者治疗管理中有用的预测生物标志物。
