Construction and validation of a histone acetylation-related lncRNA prognosis signature for ovarian cancer.

ABSTRACT

Ovarian cancer (OC) leads to the most deaths among gynecological malignancies. The various epigenetic regulatory mechanisms of histone acetylation in cancer have attracted increasing attention from scientists. Long non-coding RNA (lncRNA) also plays an important role in multiple biology processes linked to OC. This study aimed to identify the histone acetylation-related lncRNAs (HARlncRNAs) with respect to the prognosis in OC. We obtained the transcriptome data from Genotype-Tissue Expression (GTEx) project and The Cancer Genome Atlas (TCGA); HARlncRNAs were first identified by co-expression and differential expression analyses, and then univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) were used to construct the HARlncRNAs risk signature. Kaplan-Meier analysis, time-dependent receiver operating characteristics (ROC), univariate Cox regression, multivariate Cox regression, nomogram, and calibration were conducted to verify and evaluate the risk signature. Gene set enrichment analysis (GSEA) in risk groups were conducted to explore the tightly correlated pathways with the risk group. A risk signature with 14 HARlncRNAs in OC was finally established and further validated in the International Cancer Genome Consortium (ICGC) cohort; the 1-, 3-, and 5-year ROC value, nomogram, and calibration results confirmed the good prediction power of this model. The patients were grouped into high- and low-risk subgroups according to the risk score by the median value. The low-risk group patients exhibited a higher homologous recombination deficiency (HRD) score, LOH_frac_altered, and mutLoad_nonsilent. Furthermore, consensus clustering analysis was employed to divide OC patients into three clusters based on the expression of the 14 HARlncRNAs, which presented different survival probabilities. Principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE) were also performed to evaluate the three clusters. In conclusion, the risk signature composed of 14 HARlncRNAs might function as biomarkers and prognostic indicators with respect to predicting the response to the anti-cancer drugs in OC.