Wang Yanyan, Yang Fang, Zhuang Yongzhi
Department of Medical Oncology, Daqing Oilfield General Hospital, Daqing, Heilongjiang 163001, P.R. China.
Exp Ther Med. 2018 Feb;15(2):1185-1192. doi: 10.3892/etm.2017.5571. Epub 2017 Nov 27.
Long non-coding RNAs (lncRNAs) have been indicated to have prognostic roles in various cancer types. However, the association between lncRNAs and lung squamous cell carcinoma (LSCC) progression, and the prognostic value of lncRNAs as a marker for early detection of LSCC have not been systematically investigated. The present study performed a genome-wide comparative analysis in order to determine the expression profiles of 10,207 lncRNAs to investigate the expression patterns between patients with early stages of LSCC (stage I-II) and those with late-stage disease (stage III-IV). It was found that 114 lncRNAs were significantly differentially expressed between late- and early-stage LSCC and therefore associated with the progression of the malignancy. By focusing on progression-associated lncRNAs, eight lncRNAs were found to be significantly associated with overall survival of LSCC patients according to univariate Cox proportional hazards regression analysis. These eight prognostic lncRNAs were integrated into a progression-associated eight-lncRNA signature, which stratified patients into two groups with significantly different overall survival (median survival, 2.25 vs. 7.68 years; P=2.06×10). In addition, the prognostic value of the progression-associated eight-lncRNA signature was independent of known clinical factors. Functional analysis suggested that eight prognostic lncRNAs may be involved in adipocytokine signaling pathway and glycerophospholipid metabolism. Taken together, the progression-associated eight-lncRNA signature identified by our study not only represents a candidate prognostic biomarker for LSCC patients but also provides insight into the molecular mechanisms in the progression of LSCC.
长链非编码RNA(lncRNAs)已被证明在多种癌症类型中具有预后作用。然而,lncRNAs与肺鳞状细胞癌(LSCC)进展之间的关联,以及lncRNAs作为LSCC早期检测标志物的预后价值尚未得到系统研究。本研究进行了全基因组比较分析,以确定10207个lncRNAs的表达谱,从而研究LSCC早期(I-II期)患者与晚期疾病(III-IV期)患者之间的表达模式。研究发现,114个lncRNAs在LSCC晚期和早期之间存在显著差异表达,因此与恶性肿瘤进展相关。通过聚焦于与进展相关的lncRNAs,根据单变量Cox比例风险回归分析发现,8个lncRNAs与LSCC患者的总生存期显著相关。这8个预后lncRNAs被整合到一个与进展相关的八lncRNA特征中,该特征将患者分为两组,总生存期差异显著(中位生存期,2.25年对7.68年;P=2.06×10)。此外,与进展相关的八lncRNA特征的预后价值独立于已知的临床因素。功能分析表明,8个预后lncRNAs可能参与脂肪细胞因子信号通路和甘油磷脂代谢。综上所述,我们的研究确定的与进展相关的八lncRNA特征不仅代表了LSCC患者的候选预后生物标志物,还为LSCC进展的分子机制提供了见解。