Dataset Information

A seven-lncRNA signature predicts overall survival in esophageal squamous cell carcinoma.

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer and the leading causes of cancer-related mortality worldwide, especially in Eastern Asia. Here, we downloaded the microarray data of lncRNA expression profiles of ESCC patients from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data sets and divided into training, validation and test set. The random survival forest (RSF) algorithm and Cox regression analysis were applied to identify a seven-lncRNA signature. Then the predictive ability of the seven-lncRNA signature was evaluated in the validation and test set using Kaplan-Meier test, time-dependent receiver operating characteristic (ROC) curves and dynamic area under curve (AUC). Stratified analysis and multivariate Cox regression also demonstrated the independence of the signature in prognosis prediction from other clinical factors. Besides, the predict accuracy of lncRNA signature was much better than that of tumor-node-metastasis (TNM) stage in all the three sets. LncRNA combined with TNM displayed better prognostic predict ability than either alone. The role of LINC00173 from the signature in modulating the proliferation and cell cycle of ESCC cells was also observed. These results indicated that this seven-lncRNA signature could be used as an independent prognostic biomarker for prognosis prediction of patients with ESCC.

SUBMITTER: Mao Y

PROVIDER: S-EPMC5995883 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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A seven-lncRNA signature predicts overall survival in esophageal squamous cell carcinoma.

Mao Yu Y Fu Zhanzhao Z Zhang Yunjie Y Dong Lixin L Zhang Yanqiu Y Zhang Qiang Q Li Xin X Liu Jia J

Scientific reports 20180611 1

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer and the leading causes of cancer-related mortality worldwide, especially in Eastern Asia. Here, we downloaded the microarray data of lncRNA expression profiles of ESCC patients from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data sets and divided into training, validation and test set. The random survival forest (RSF) algorithm and Cox regression analysis were applied to identify a seven-lnc ...[more]

PMID: 29891973

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Project description:BackgroundIncreasing 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.MethodsBased 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.ResultsA 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.ConclusionsThe three-lncRNA signature is a novel and potential predictor of OS and DFS for patients with ESCC.

Project description:BACKGROUND:Long non-coding RNAs (lncRNAs) have been reported to be prognostic biomarkers in many types of cancer. We aimed to identify a lncRNA signature that can predict the prognosis in patients with esophageal squamous cell carcinoma (ESCC). METHODS:Using a custom microarray, we retrospectively analyzed lncRNA expression profiles in 141 samples of ESCC and 81 paired non-cancer specimens from Sun Yat-Sen University Cancer Center (Guangzhou, China), which were used as a training cohort to identify a signature associated with clinical outcomes. Then we conducted quantitative RT-PCR in another 103 samples of ESCC from the same cancer center as an independent cohort to verify the signature. RESULTS:Microarray analysis showed that there were 338 lncRNAs significantly differentially expressed between ESCC and non-cancer esophagus tissues in the training cohort. From these differentially expressed lncRNAs, we found 16 lncRNAs associated with overall survival (OS) of ESCC patients using Cox regression analysis. Then a 7-lncRNA signature for predicting survival was identified from the 16 lncRNAs, which classified ESCC patients into high-risk and low-risk groups. Patients with high-risk have shorter OS (HR: 3.555, 95% CI 2.195-5.757, p?<?0.001) and disease-free survival (DFS) (HR: 2.537, 95% CI 1.646-3.909, p?<?0.001) when compared with patients with low-risk in the training cohort. In the independent cohort, the 7 lncRNAs were detected by qRT-PCR and used to compute risk score for the patients. The result indicates that patients with high risk also have significantly worse OS (HR?=?2.662, 95% CI 1.588-4.464, p?<?0.001) and DFS (HR 2.389, 95% CI 1.447-3.946, p?<?0.001). The univariate and multivariate Cox regression analyses indicate that the signature is an independent factor for predicting survival of patients with ESCC. Combination of the signature and TNM staging was more powerful in predicting OS than TNM staging alone in both the training (AUC: 0.772 vs 0.681, p?=?0.002) and independent cohorts (AUC: 0.772 vs 0.660, p?=?0.003). CONCLUSIONS:The 7-lncRNA signature is a potential prognostic biomarker in patients with ESCC and may help in treatment decision when combined with the TNM staging system.

Dataset Information

A seven-lncRNA signature predicts overall survival in esophageal squamous cell carcinoma.

Publications

A seven-lncRNA signature predicts overall survival in esophageal squamous cell carcinoma.

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