A Novel Three-LncRNA Signature Predicting Tumor Recurrence in Nonfunctioning Pituitary Adenomas

Abstract

The nonfunctioning pituitary adenoma (NFPA) recurrence rate is relatively high after surgical resection. Here, we constructed effective long noncoding RNA (lncRNA) signatures to predict NFPA prognosis. LncRNAs expression microarray sequencing profiles were obtained from 66 NFPAs. Sixty-six patients were randomly separated into a training (n = 33) and test group (n = 33). Univariable Cox regression and a machine learning algorithm was used to filter lncRNAs. Time-dependent receiver operating characteristic (ROC) analysis was performed to improve the prediction signature. Three lncRNAs (LOC101927765, RP11-23N2.4 and RP4-533D7.4) were included in a prognostic signature with high prediction accuracy for tumor recurrence, which had the largest area under ROC curve (AUC) value in the training/test group (AUC = 0.87/0.73). The predictive ability of the signature was validated by Kaplan-Meier survival analysis. A signature-based risk score model divied patients into two risk group, and the recurrence-free survival rates of the groups were significantly different (log-rank p < 0.001). In addition, the ROC analysis showed that the lncRNA signature predictive ability was significantly better than that of age in the training/testing/entire group (AUC = 0.87/0.726/0.798 vs. AUC = 0.683/0.676/0.679). We constructed and verified a three-lncRNA signature predictive of recurrence, suggesting potential therapeutic targets for NFPA.

Recent advances in understanding and managing pituitary adenomas

“…Differences in histone modification and DNA methylation have been observed between NFPAs with and without postsurgical progression 37 , and in comparison with somatotroph adenomas 38 . Three lncRNAs (LOC101927765, RP11-23N2.4, and RP4-533D7.4) have been associated with NFPA recurrence 39 .…”