Prognostic Value of a Four-miRNA Signature in Patients With Lymph Node Positive Locoregional Esophageal Squamous Cell Carcinoma Undergoing Complete Surgical Resection

May 7, 2019Annals of surgery

Four microRNA markers linked to outcomes in patients with lymph node positive esophageal cancer after surgery

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Abstract

A 4-miRNA based classifier identified high and low-risk groups among lymph node-positive locoregional esophageal squamous cell carcinoma patients.

Twenty miRNAs associated with esophageal squamous cell carcinoma were identified and validated.
Patients classified as high-risk by the classifier had a significantly lower 5-year overall survival rate of 8.7% compared to 50.3% for low-risk patients.
The classifier demonstrated strong prognostic accuracy in both internal testing and independent validation sets.
Multivariate survival analyses indicated that the classifier serves as an independent prognostic factor.
Combining the 4-miRNA based classifier with clinicopathological factors enhanced the accuracy of survival predictions.

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OBJECTIVE: This study was intended to identify prognostic biomarkers for lymph node (LN)-positive locoregional esophageal squamous cell carcinoma (ESCC) patients.

SUMMARY OF BACKGROUND DATA: Surgery is a major treatment for LN-positive locoregional ESCC patients in China. However, patient outcomes are poor and heterogeneous.

METHODS: ESCC-associated miRNAs were identified by microarray and validated by quantitative real-time polymerase chain reaction analyses in ESCC and normal esophageal epithelial samples. A multi-miRNA based classifier was established using a least absolute shrinkage and selection operator model in a training set of 145 LN-positive locoregional ESCCs, and further assessed in internal testing and independent validation sets of 145 and 243 patients, respectively.

RESULTS: Twenty ESCC-associated miRNAs were identified and validated. A 4-miRNA based classifier (miR-135b-5p, miR-139-5p, miR-29c-5p, and miR-338-3p) was generated to classify LN-positive locoregional ESCC patients into high and low-risk groups. Patients with high-risk scores in the training set had a lower 5-year overall survival rate [8.7%, 95% confidence interval (CI): 0-20.3] than those with low-risk scores (50.3%, 95% CI: 40.0-60.7; P < 0.0001). The prognostic accuracy of the classifier was validated in the internal testing (P < 0.0001) and independent validation sets (P = 0.00073). Multivariate survival analyses showed that the 4-miRNA based classifier was an independent prognostic factor, and the combination of the 4-miRNA based classifier and clinicopathological prognostic factors significantly improved the prognostic accuracy of clinicopathological prognostic factors alone.

CONCLUSION: Our 4-miRNA based classifier is a reliable prognostic prediction tool for overall survival in LN-positive locoregional ESCC patients and might offer a novel probability of ESCC treatment individualization.

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Prognostic Value of a Four-miRNA Signature in Patients With Lymph Node Positive Locoregional Esophageal Squamous Cell Carcinoma Undergoing Complete Surgical Resection

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