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High expression of SCHLAP1 in primary prostate cancer is an independent predictor of biochemical recurrence, despite substantial heterogeneity
Neoplasia ( IF 6.3 ) Pub Date : 2021-06-07 , DOI: 10.1016/j.neo.2021.05.012
Susanne G Kidd 1 , Kristina T Carm 1 , Mari Bogaard 2 , Linn Guro Olsen 3 , Anne Cathrine Bakken 3 , Marthe Løvf 3 , Ragnhild A Lothe 1 , Karol Axcrona 4 , Ulrika Axcrona 5 , Rolf I Skotheim 6
Affiliation  

In primary prostate cancer, the common multifocality and heterogeneity are major obstacles in finding robust prognostic tissue biomarkers. The long noncoding RNA SCHLAP1 has been suggested, but its prognostic value has not been investigated in the context of tumor heterogeneity. In the present study, expression of SCHLAP1 was investigated using real-time RT-PCR in a multisampled series of 778 tissue samples from radical prostatectomies of 164 prostate cancer patients (median follow-up time 7.4 y). The prognostic value of SCHLAP1 was evaluated with biochemical recurrence as endpoint.

In total, 29% of patients were classified as having high expression of SCHLAP1 in at least one malignant sample. Among these, inter- and intrafocal heterogeneity was detected in 72% and 56%, respectively. High expression of SCHLAP1 was shown to be a predictor of biochemical recurrence in both uni- and multivariable cox regression analyses (P < 0.001 and P = 0.02). High expression of SCHLAP1 was also significantly associated with adverse clinicopathological characteristics, including grade group, high pT stage, invasive cribriform growth/intraductal carcinoma of the prostate, and reactive stroma. In conclusion, high expression of SCHLAP1 in at least one malignant sample is a robust prognostic biomarker in primary prostate cancer. For the first time, high SCHLAP1 expression has been associated with the aggressive histopathologic feature reactive stroma. The expression of SCHLAP1 is highly heterogeneous, and analysis of multiple samples is therefore crucial in determination of the SCHLAP1 status of a patient.



中文翻译:

尽管存在显着的异质性,但原发性前列腺癌中 SCHLAP1 的高表达是生化复发的独立预测因子

在原发性前列腺癌中,常见的多灶性和异质性是寻找稳健的预后组织生物标志物的主要障碍。长链非编码 RNA SCHLAP1已被提出,但其预后价值尚未在肿瘤异质性的背景下进行研究。在本研究中,使用实时 RT-PCR 在来自 164 名前列腺癌患者根治性前列腺切除术的 778 个组织样本的多重采样系列中研究了 SCHLAP1 的表达(中位随访时间 7.4 年)以生化复发作为终点来评估SCHLAP1的预后价值。

总共有 29% 的患者被归类为在至少一份恶性样本中SCHLAP1高表达。其中,检测到焦点间和焦点内异质性的比例分别为 72% 和 56%。在单变量和多变量 cox 回归分析中, SCHLAP1的高表达被证明是生化复发的预测因子(P < 0.001 和P = 0.02)。SCHLAP1的高表达还与不良临床病理特征显着相关,包括分级组、高pT分期、侵袭性筛状生长/前列腺导管内癌和反应性基质。总之,至少一个恶性样本中SCHLAP1的高表达是原发性前列腺癌的一个强有力的预后生物标志物。首次将SCHLAP1高表达与侵袭性组织病理学特征反应性基质相关联。SCHLAP1的表达具有高度异质性,因此多个样本的分析对于确定患者的SCHLAP1状态至关重要。

更新日期:2021-06-07
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