Protein-coding genes combined with long non-coding RNAs predict prognosis in esophageal squamous cell carcinoma patients as a novel clinical multi-dimensional signature

Oct 8, 2016Molecular bioSystems

Protein and long non-coding RNA levels together predict outcomes in esophageal squamous cell cancer patients

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Abstract

A signature of three protein-coding genes and two long non-coding RNAs predicts overall survival in esophageal squamous cell carcinoma with an area under the ROC curve of 0.85.

The three protein-coding genes identified are ANGPTL7, OBP2A, and SLC27A5.
The two long non-coding RNAs identified are RP11-702B10.1 and RP11-523H24.3.
In the training group, the signature was significantly associated with survival, showing a median survival of 32.2 months compared to over 60 months for those not in the high-risk group (P < 0.001).
In the test group, the signature also indicated a median survival of 39.3 months versus over 60 months (P = 0.03).
The signature is suggested to be an independent prognostic factor for patients with esophageal squamous cell carcinoma.
Combining the signature with the TNM stage may better categorize the prognosis of esophageal squamous cell carcinoma patients.

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Esophageal carcinoma is one of the most malignant gastrointestinal cancers worldwide, and has a high mortality rate. Both protein-coding genes (PCGs) and long non-coding RNAs (lncRNAs) have been shown to play an important role in the development of malignant tumors. However, the clinical significance of PCGs combined lncRNAs is yet to be investigated in esophageal squamous cell carcinoma (ESCC). Using probe re-annotation, univariable Cox regression and the random survival forest algorithm to identify PCG-lncRNA combinations predictive of the overall survival, we found a signature comprised of three PCGs (ANGPTL7, OBP2A, SLC27A5) and two lncRNAs (RP11-702B10.1, RP11-523H24.3) to have the highest accurate prediction, with an area under ROC curve (AUC) of 0.85 in the training group and 0.63 in the test group, and it was significantly associated with the survival of ESCC patients in the training group (median survival: 32.2 months > 60 months, P < 0.001). The application of the signature to the test group showed similar prognostic values (median survival: 39.3 months vs. >60 months, P = 0.03). The chi-square test and multivariable Cox regression analysis showed that the three-PCG, two-lncRNA signature was an independent prognostic factor for patients with ESCC. Stratified analysis suggested that the PCG-lncRNA signature combined with the TNM stage could more accurately categorize ESCC patients. Our study suggests that the three-PCG, two-lncRNA signature has clinical significance for the prognosis of patients with ESCC. This signature can serve as a potential auxiliary biomarker of the TNM stage to subdivide ESCC patients more precisely.

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Protein-coding genes combined with long non-coding RNAs predict prognosis in esophageal squamous cell carcinoma patients as a novel clinical multi-dimensional signature

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