Glaser Zachary A, Love Harold D, Guo Shunhua, Gellert Lan, Chang Sam S, Herrell Stanley Duke, Barocas Daniel A, Penson David F, Cookson Michael S, Clark Peter E
Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN.
Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN.
Urol Oncol. 2017 May;35(5):286-293. doi: 10.1016/j.urolonc.2016.12.012. Epub 2017 Jan 17.
Our aims were to determine if targeting protein for Xklp2 (TPX2) is correlated with clear cell renal cell carcinoma (ccRCC) histology and oncologic outcomes using The Cancer Genome Atlas (TCGA) and an institutional tissue microarray (TMA).
Clinicopathological data obtained from the TCGA consisted of 415 samples diagnosed with ccRCC. A TMA was constructed from tumors of 207 patients who underwent radical nephrectomy for ccRCC. TPX2 expression by immunohistochemistry on TMA was assessed by a genitourinary pathologist. Clinical data were extracted and linked to TMA cores. TPX2 and Aurora-A mRNA coexpression were evaluated in the TCGA cohort. Overall survival (OS), cancer-specific survival, and recurrence-free survival (RFS) were analyzed using the Kaplan-Meier method and log-rank statistics. Univariate and multivariate analyses were conducted using Cox proportional hazard models.
Median follow-up time for the TCGA cohort was 3.07 years. Aurora-A and TPX2 mRNA coexpression were significantly correlated (Pearson correlation = 0.918). High TPX2 mRNA expression was associated with advanced stage, metastasis, poor OS, and RFS. Median follow-up time for the TMA cohort was 5.3 years. Elevated TPX2 protein expression, defined as greater than 75th percentile staining intensity, was identified in 47/207 (22.7%) patients. Increased TPX2 immunostaining was associated with poor OS (P = 0.0327, 53% 5-year mortality), cancer-specific survival (P<0.01, 47.8% 5-year cancer-specific mortality), RFS (P = 0.0313, 73.6%, 5-year recurrence rate), grade, T stage, and metastasis. Multivariate analysis demonstrated elevated expression served as an independent predictor of RFS (hazard ratio = 3.62 (1.13-11.55), P = 0.029).
We show TPX2, a regulator of Aurora-A, is associated with high grade and stage of ccRCC, and is an independent predictor of recurrence. Future studies are warranted testing its role in ccRCC biology, and its potential as a therapeutic target.
我们的目标是使用癌症基因组图谱（TCGA）和机构组织微阵列（TMA）来确定Xklp2靶向蛋白（TPX2）是否与透明细胞肾细胞癌（ccRCC）的组织学及肿瘤学预后相关。
从TCGA获得的临床病理数据包括415例诊断为ccRCC的样本。一个TMA由207例因ccRCC接受根治性肾切除术患者的肿瘤构建而成。泌尿生殖病理学家通过免疫组织化学评估TMA上的TPX2表达。提取临床数据并将其与TMA核心样本相关联。在TCGA队列中评估TPX2和Aurora - A mRNA的共表达情况。使用Kaplan - Meier方法和对数秩统计分析总生存期（OS）、癌症特异性生存期和无复发生存期（RFS）。使用Cox比例风险模型进行单因素和多因素分析。
TCGA队列的中位随访时间为3.07年。Aurora - A和TPX2 mRNA共表达显著相关（Pearson相关系数 = 0.918）。高TPX2 mRNA表达与晚期、转移、较差的OS和RFS相关。TMA队列的中位随访时间为5.3年。在47/207（22.7%）例患者中鉴定出TPX2蛋白表达升高，定义为染色强度大于第75百分位数。TPX2免疫染色增加与较差的OS（P = 0.0327，5年死亡率53%）、癌症特异性生存期（P<0.01，5年癌症特异性死亡率47.8%）、RFS（P = 0.0313，5年复发率73.6%）、分级、T分期和转移相关。多因素分析表明表达升高是RFS的独立预测因子（风险比 = 3.62（1.13 - 11.55），P = 0.029）。
我们表明，Aurora - A的调节因子TPX2与ccRCC的高级别和晚期相关，并且是复发的独立预测因子。未来的研究有必要测试其在ccRCC生物学中的作用及其作为治疗靶点的潜力。
