White-Al Habeeb Nicole M, Di Meo Ashley, Scorilas Andreas, Rotondo Fabio, Masui Olena, Seivwright Annetta, Gabril Manal, Girgis Andrew H A, Jewett Michael A, Yousef George M
Department of Laboratory Medicine, and the Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada,
Clin Exp Metastasis. 2015 Aug;32(6):531-41. doi: 10.1007/s10585-015-9725-2. Epub 2015 Jun 3.
Clear cell renal cell carcinoma (ccRCC) is an aggressive disease with unpredictable behaviour. Clinical parameters are not always accurate for prognosis prediction. The integration of molecular markers to prognostic models can significantly improve prognostic assessment and consequently patient management. We assessed the expression of alpha-enolase (ENO1) protein by immunohistochemistry in 360 patients with primary ccRCC and correlated its expression with multiple clinicopathological parameters including stage, grade, tumor size, disease-free and overall survival. Cox proportional hazard regression models adjusted for clinicopathological factors were used to test for a link between ENO1 expression and both disease-free and overall survival. We correlated ENO1 mRNA expression with overall survival in an independent set of 428 ccRCC cases from The Cancer Genome Atlas. ENO1 showed cytoplasmic, membranous and nuclear staining patterns. There is a statistically significant negative correlation between ENO1 expression, tumor stage, and grade. ENO1 expression also shows a statistically significant direct correlation with disease-free survival (p = 0.011) and overall survival (p = 0.030) in ccRCC. Patients with higher ENO1 expression had lower hazard ratio of recurrence, although this was not statistically significant (HR = 0.330, p = 0.060). These findings were validated at the mRNA level in an independent set of 428 ccRCC cases which also showed that low ENO1 expression is associated with significantly shorter overall survival. Down-regulation of ENO1 can be a predictor of poor prognosis in ccRCC, and it can be a potential prognostic marker.
透明细胞肾细胞癌（ccRCC）是一种侵袭性疾病，其行为难以预测。临床参数在预测预后方面并不总是准确的。将分子标志物整合到预后模型中可显著改善预后评估，从而改善患者管理。我们通过免疫组织化学评估了360例原发性ccRCC患者中α-烯醇化酶（ENO1）蛋白的表达，并将其表达与包括分期、分级、肿瘤大小、无病生存期和总生存期在内的多个临床病理参数相关联。使用针对临床病理因素进行调整的Cox比例风险回归模型来测试ENO1表达与无病生存期和总生存期之间的联系。我们在来自癌症基因组图谱的428例ccRCC病例的独立数据集中将ENO1 mRNA表达与总生存期相关联。ENO1表现出细胞质、膜和核染色模式。ENO1表达与肿瘤分期和分级之间存在统计学上显著的负相关。在ccRCC中，ENO1表达与无病生存期（p = 0.011）和总生存期（p = 0.030）也呈现出统计学上显著的正相关。ENO1表达较高的患者复发风险比更低，尽管这在统计学上不显著（HR = 0.330，p = 0.060）。这些发现在428例ccRCC病例的独立数据集中在mRNA水平上得到了验证，该数据集还表明ENO1低表达与显著缩短的总生存期相关。ENO1的下调可能是ccRCC预后不良的一个预测指标，并且它可能是一种潜在的预后标志物。
