长链非编码 RNA CASC9 的上调可作为鳞状细胞癌的生物标志物。
Upregulation of the long non-coding RNA CASC9 as a biomarker for squamous cell carcinoma.
机构信息
Department of Urology, Medical Faculty, Heinrich Heine University Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany.
Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
出版信息
BMC Cancer. 2019 Aug 14;19(1):806. doi: 10.1186/s12885-019-6021-6.
BACKGROUND
Few diagnostic and prognostic biomarkers are available for head-and-neck squamous cell carcinoma (HNSCC). Long non-coding RNAs (lncRNAs) have shown promise as biomarkers in other cancer types and in some cases functionally contribute to tumor development and progression. Here, we searched for lncRNAs useful as biomarkers in HNSCC.
METHODS
Public datasets were mined for lncRNA candidates. Two independent HNSCC tissue sets and a bladder cancer tissue set were analyzed by RT-qPCR. Effects of lncRNA overexpression or downregulation on cell proliferation, clonogenicity, migration and chemosensitivity were studied in HNSCC cell lines.
RESULTS
Data mining revealed prominently CASC9, a lncRNA significantly overexpressed in HNSCC tumor tissues according to the TCGA RNAseq data. Overexpression was confirmed by RT-qPCR analyses of patient tissues from two independent cohorts. CASC9 expression discriminated tumors from normal tissues with even higher specificity than HOTAIR, a lncRNA previously suggested as an HNSCC biomarker. Specificity of HNSCC detection by CASC9 was further improved by combination with HOTAIR. Analysis of TCGA pan-cancer data revealed significant overexpression of CASC9 across different other entities including bladder, liver, lung and stomach cancers and especially in squamous cell carcinoma (SCC) of the lung. By RT-qPCR analysis we furthermore detected stronger CASC9 overexpression in pure SCC of the urinary bladder and mixed urothelial carcinoma with squamous differentiation than in pure urothelial carcinomas. Thus, CASC9 might represent a general diagnostic biomarker and particularly for SCCs. Unexpectedly, up- or downregulation of CASC9 expression in HNSCC cell lines with low or high CASC9 expression, respectively, did not result in significant changes of cell viability, clonogenicity, migration or chemosensitivity.
CONCLUSIONS
CASC9 is a promising biomarker for HNSCC detection. While regularly overexpressed, however, this lncRNA does not seem to act as a major driver of development or progression in this tumor.
背景
目前用于头颈部鳞状细胞癌（HNSCC）的诊断和预后生物标志物较少。长链非编码 RNA（lncRNA）在其他癌症类型中作为生物标志物显示出潜力，并且在某些情况下，它们在肿瘤的发生和发展中具有功能作用。在这里，我们寻找可作为 HNSCC 生物标志物的 lncRNA。
方法
挖掘公共数据集以获取 lncRNA 候选物。通过 RT-qPCR 分析两个独立的 HNSCC 组织集和一个膀胱癌组织集。在 HNSCC 细胞系中研究 lncRNA 过表达或下调对细胞增殖、集落形成、迁移和化疗敏感性的影响。
结果
数据挖掘显示，根据 TCGA RNAseq 数据，CASC9 在 HNSCC 肿瘤组织中显著过表达，是一种重要的 lncRNA。通过两个独立队列的患者组织 RT-qPCR 分析证实了 CASC9 的过表达。CASC9 表达可区分肿瘤与正常组织，其特异性甚至高于以前被认为是 HNSCC 生物标志物的 HOTAIR。CASC9 与 HOTAIR 结合可进一步提高 HNSCC 检测的特异性。对 TCGA 泛癌数据的分析显示，CASC9 在不同实体瘤中包括膀胱癌、肝癌、肺癌和胃癌以及肺鳞癌中均有显著过表达。通过 RT-qPCR 分析，我们还发现纯膀胱鳞状细胞癌和混合尿路上皮癌伴鳞状分化中 CASC9 的过表达明显强于纯尿路上皮癌。因此，CASC9 可能代表一种通用的诊断生物标志物，特别是对于 SCC。出乎意料的是，在 CASC9 表达水平低或高的 HNSCC 细胞系中上调或下调 CASC9 表达，并没有导致细胞活力、集落形成、迁移或化疗敏感性的显著变化。
结论
CASC9 是一种有前途的 HNSCC 检测生物标志物。然而，尽管 CASC9 经常过表达，但它似乎不是这种肿瘤发生和发展的主要驱动因素。
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