Fawzy Manal S, Toraih Eman A, El-Wazir Aya, Hosny Marwa M, Badran Dahlia I, El Kelish Amr
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia.
Arch Med Sci. 2019 May 17;17(4):1016-1027. doi: 10.5114/aoms.2019.85201. eCollection 2021.
Long intergenic non-coding RNA, regulator of reprogramming (LINC-ROR) is a newly identified cytoplasmic long non-coding RNA (lncRNA) implicated in cell longevity and apoptosis. We aimed in the current work for the first time to investigate the association of the expression profiles of LINC-ROR and three stem-related transcriptional factors with clinicopathological data and their impact on renal cell carcinoma (RCC) progression in a sample of RCC patients.
Expression levels of LINC-ROR and stemness-related factors: SOX2, NANOG, and POU5F1 were detected in 60 formalin-fixed, paraffin-embedded tissues, and their paired adjacent non-cancer tissues ( = 60) by using real-time qRT-PCR analysis. Additionally, the expression profiles were compared with the available clinicopathological features.
The genes studied were markedly up-regulated in RCC (medians and interquartile ranges were 30.3 (1.84-235.5), 10.2 (1.84-53.9), 5.39 (0.94-23.5), and 12.5 (1.61-43.2) for , , , and , respectively) relative to paired non-cancer tissue. High expression levels were associated with poor prognosis in terms of tumour undifferentiation (for , and ), lymph node infiltration (for ), postoperative recurrence (for and ), and shorter overall survival (OS) and progression-free survival (for all genes studied). The best curve for OS prediction was constructed with LINC-ROR data (area under the receiver operating characteristic curve (AUC) = 0.804 at a cut-off value of 72.7, sensitivity 78.9%, and specificity 80.5%).
Collectively, aberrant LINC-ROR and pluripotent gene expression may be recognised as prognostic markers for RCC. Future functional studies are highly recommended to validate the study findings.
长链基因间非编码RNA，重编程调节因子（LINC-ROR）是一种新发现的细胞质长链非编码RNA（lncRNA），与细胞寿命和凋亡有关。我们在当前工作中首次旨在研究LINC-ROR和三种干细胞相关转录因子的表达谱与临床病理数据之间的关联，以及它们对一组肾细胞癌（RCC）患者样本中肾细胞癌进展的影响。
通过实时定量逆转录聚合酶链反应（qRT-PCR）分析，检测60例福尔马林固定、石蜡包埋组织及其配对的相邻非癌组织（n = 60）中LINC-ROR和干性相关因子SOX2、NANOG及POU5F1的表达水平。此外，将表达谱与可用的临床病理特征进行比较。
相对于配对的非癌组织，所研究的基因在RCC中显著上调（LINC-ROR、SOX2、NANOG和POU5F1的中位数及四分位数间距分别为30.3（1.84 - 235.5）、10.2（1.84 - 53.9）、5.39（0.94 - 23.5）和12.5（1.61 - 43.2））。高表达水平与肿瘤未分化（对于LINC-ROR、SOX2和NANOG）、淋巴结浸润（对于LINC-ROR）、术后复发（对于LINC-ROR和POU5F1）及较短的总生存期（OS）和无进展生存期（对于所有研究基因）方面的不良预后相关。用LINC-ROR数据构建的OS预测最佳曲线（受试者操作特征曲线下面积（AUC）在截断值为72.7时为0.804，敏感性为78.9%，特异性为80.5%）。
总体而言，异常的LINC-ROR和多能基因表达可能被视为RCC的预后标志物。强烈建议未来进行功能研究以验证本研究结果。
