一个三长链非编码 RNA 标志物可预测食管鳞癌患者的总生存期和无病生存期。
A three-lncRNA signature predicts overall survival and disease-free survival in patients with esophageal squamous cell carcinoma.
机构信息
Institute of Oncologic Pathology, Shantou University Medical College, No. 22, Xinling Road, Shantou, Guangdong, 515041, China.
The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, 515041, Guangdong, People's Republic of China.
出版信息
BMC Cancer. 2018 Feb 6;18(1):147. doi: 10.1186/s12885-018-4058-6.
BACKGROUND
Increasing evidence shows that dysregulated long non-coding RNAs (lncRNAs) can serve as potential biomarkers for cancer prognosis. However, lncRNA signatures, as potential prognostic biomarkers for esophageal squamous cell carcinoma (ESCC), have been seldom reported.
METHODS
Based on our previous transcriptome RNA sequencing analysis from 15 paired ESCC tissues and adjacent normal tissues, we selected 10 lncRNAs with high score rank and characterized the expression of those lncRNAs, by qRT-PCR, in 138 ESCC and paired adjacent normal samples. These 138 patients were divided randomly into training (n = 77) and test (n = 59) groups. A prognostic signature of lncRNAs was identified in the training group and validated in the test group and in an independent cohort (n = 119). Multivariable Cox regression analysis evaluated the independence of the signature in overall survival (OS) and disease-free survival (DFS) prediction. GO and KEGG pathway analysis, combined with cell transwell and proliferation assays, are applied to explore the function of the three lncRNAs.
RESULTS
A novel three-lncRNA signature, comprised of RP11-366H4.1.1 (ENSG00000248370), LINC00460 (ENSG00000233532) and AC093850.2 (ENSG00000230838), was identified. The signature classified patients into high-risk and low-risk groups with different overall survival (OS) and disease-free survival (DFS). For the training group, median OS: 23.1 months vs. 39.1 months, P < 0.001; median DFS: 15.2 months vs. 33.3 months, P < 0.001. For the test group, median OS: 23 months vs. 59 months, P < 0.001; median DFS: 16.4 months vs. 50.8 months, P < 0.001. For the independent cohort, median OS: 22.4 months vs. 60.4 months, P < 0.001). The signature indicates that patients in the high-risk group show poor OS and DFS, whereas patients with a low-risk group show significantly better outcome. The independence of the signature was validated by multivariable Cox regression analysis. GO and KEGG pathway analysis for 588 protein-coding genes-associated with the three lncRNAs indicated that the three lncRNAs were involved in tumorigenesis. In vitro assays further demonstrated that the three lncRNAs promoted the migration and proliferation of ESCC cells.
CONCLUSIONS
The three-lncRNA signature is a novel and potential predictor of OS and DFS for patients with ESCC.
背景
越来越多的证据表明，失调的长非编码 RNA（lncRNA）可以作为癌症预后的潜在生物标志物。然而，lncRNA 特征作为食管鳞状细胞癌（ESCC）的潜在预后生物标志物，很少有报道。
方法
基于我们之前从 15 对 ESCC 组织和相邻正常组织的转录组 RNA 测序分析，我们选择了 10 个具有高评分等级的 lncRNA，并通过 qRT-PCR 在 138 个 ESCC 及配对的相邻正常样本中对这些 lncRNA 的表达进行了特征分析。这 138 名患者被随机分为训练组（n=77）和测试组（n=59）。在训练组中确定了 lncRNA 的预后特征，并在测试组和独立队列（n=119）中进行了验证。多变量 Cox 回归分析评估了该特征在总生存（OS）和无病生存（DFS）预测中的独立性。GO 和 KEGG 通路分析，结合细胞转染和增殖实验，用于探索三个 lncRNA 的功能。
结果
发现了一个由 RP11-366H4.1.1（ENSG00000248370）、LINC00460（ENSG00000233532）和 AC093850.2（ENSG00000230838）组成的新型三 lncRNA 特征。该特征将患者分为高风险和低风险组，具有不同的总生存（OS）和无病生存（DFS）。对于训练组，中位 OS：23.1 个月 vs. 39.1 个月，P<0.001；中位 DFS：15.2 个月 vs. 33.3 个月，P<0.001。对于测试组，中位 OS：23 个月 vs. 59 个月，P<0.001；中位 DFS：16.4 个月 vs. 50.8 个月，P<0.001。对于独立队列，中位 OS：22.4 个月 vs. 60.4 个月，P<0.001）。该特征表明，高危组患者的 OS 和 DFS 较差，而低危组患者的预后明显更好。该特征的独立性通过多变量 Cox 回归分析得到了验证。与三个 lncRNA 相关的 588 个编码蛋白基因的 GO 和 KEGG 通路分析表明，这三个 lncRNA 参与了肿瘤发生。体外实验进一步证明了这三个 lncRNA 促进了 ESCC 细胞的迁移和增殖。
结论
三 lncRNA 特征是 ESCC 患者 OS 和 DFS 的一种新的潜在预测因子。
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