Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
Urol Oncol. 2020 May;38(5):496-505. doi: 10.1016/j.urolonc.2019.11.010. Epub 2019 Dec 18.
Polymerase I and transcript release factor (PTRF) has been implicated in cancer biology but its role in upper tract urothelial carcinoma (UTUC) is unknown. From a pilot transcriptome, we identified PTRF was significantly upregulated in high stage UTUC. Bladder cancer transcriptome from The Cancer Genome Atlas (TCGA) supported our finding and high PTRF level also predicted poor survival. We, therefore, investigated the correlation of PTRF with patients' clinicopathologic characteristics and outcomes in a multiracial UTUC cohort.
By immunohistochemical staining, PTRF expression was determined using H-score. PTRF expression of 575 UTUCs from 8 institutions, including 118 Asians and 457 Caucasians, was compared with various clinicopathologic parameters. Human urothelial cancer cell lines were used to evaluate the level of PTRF protein and mRNA expression, and PTRF transcript level was assessed in fresh samples from 12 cases of the cohort. The impact of PTRF expression on disease progression, cancer-specific death and overall mortality was also examined.
High PTRF expression was significantly associated with multifocality (P = 0.023), high pathologic tumor stage (P < 0.00001), nonurothelial differentiation (P = 0.035), lymphovascular invasion (P = 0.003) and lymph node metastasis (P = 0.031). PTRF mRNA expression was also markedly increased in advanced stage UTUC (P = 0.0003). High PTRF expressing patients had consistently worse outcomes than patients with low PTRF expression regardless of demographic variation (all P < 0.005). In multivariate analysis, high PTRF expression was an independent predictor for progression-free survival (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.07-2.69, P = 0.025), cancer-specific survival (HR 2.09, 95% CI 1.28-3.42, P = 0.003), and overall survival (HR 2.04, 95% CI 1.33-3.14, P = 0.001).
Results indicate that PTRF is a predictive biomarker for progression and survival and an independent prognosticator of UTUC. Elevated PTRF could probably propel clinically aggressive disease and serve as a potential therapeutic target for UTUC.
多聚酶 I 和转录释放因子（PTRF）已被牵涉到癌症生物学中，但它在上尿路上皮癌（UTUC）中的作用尚不清楚。从一个初步的转录组中，我们发现 PTRF 在高分期 UTUC 中显著上调。来自癌症基因组图谱（TCGA）的膀胱癌转录组支持了我们的发现，并且高水平的 PTRF 也预示着较差的生存。因此，我们在一个多民族 UTUC 队列中调查了 PTRF 与患者临床病理特征和结局的相关性。
通过免疫组织化学染色，使用 H 评分确定 PTRF 表达。比较了来自 8 个机构的 575 例 UTUC 患者的 PTRF 表达，包括 118 名亚洲人和 457 名高加索人，与各种临床病理参数进行比较。用人尿路上皮癌细胞系评估 PTRF 蛋白和 mRNA 表达水平，并评估队列中 12 例患者的新鲜样本中的 PTRF 转录水平。还检查了 PTRF 表达对疾病进展、癌症特异性死亡和总死亡率的影响。
高 PTRF 表达与多灶性（P=0.023）、高病理肿瘤分期（P<0.00001）、非尿路上皮分化（P=0.035）、淋巴血管侵犯（P=0.003）和淋巴结转移（P=0.031）显著相关。在高级别 UTUC 中，PTRF mRNA 表达也明显增加（P=0.0003）。高 PTRF 表达患者的结局明显差于低 PTRF 表达患者，无论人口统计学差异如何（均 P<0.005）。在多变量分析中，高 PTRF 表达是无进展生存期（危险比 [HR]1.70，95%置信区间 [CI]1.07-2.69，P=0.025）、癌症特异性生存期（HR 2.09，95%CI1.28-3.42，P=0.003）和总生存期（HR 2.04，95%CI1.33-3.14，P=0.001）的独立预测因子。
结果表明，PTRF 是进展和生存的预测生物标志物，也是 UTUC 的独立预后标志物。升高的 PTRF 可能会促进临床上侵袭性疾病，并可能成为 UTUC 的潜在治疗靶点。
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