Comprehensive Analysis of the Prognostic Signature of Mutation-Derived Genome Instability-Related lncRNAs for Patients With Endometrial Cancer

Abstract

Background: Emerging evidence shows that genome instability-related long non-coding RNAs (lncRNAs) contribute to tumor–cell proliferation, differentiation, and metastasis. However, the biological functions and molecular mechanisms of genome instability-related lncRNAs in endometrial cancer (EC) are underexplored.Methods: EC RNA sequencing and corresponding clinical data obtained from The Cancer Genome Atlas (TCGA) database were used to screen prognostic lncRNAs associated with genomic instability via univariate and multivariate Cox regression analysis. The genomic instability-related lncRNA signature (GILncSig) was developed to assess the prognostic risk of high- and low-risk groups. The prediction performance was analyzed using receiver operating characteristic (ROC) curves. The immune status and mutational loading of different risk groups were compared. The Genomics of Drug Sensitivity in Cancer (GDSC) and the CellMiner database were used to elucidate the relationship between the correlation of prognostic lncRNAs and drug sensitivity. Finally, we used quantitative real-time PCR (qRT-PCR) to detect the expression levels of genomic instability-related lncRNAs in clinical samples.Results: GILncSig was built using five lncRNAs (AC007389.3, PIK3CD-AS2, LINC01224, AC129507.4, and GLIS3-AS1) associated with genomic instability, and their expression levels were verified using qRT-PCR. Further analysis revealed that risk score was negatively correlated with prognosis, and the ROC curve demonstrated the higher accuracy of GILncSig. Patients with a lower risk score had higher immune cell infiltration, a higher immune score, lower tumor purity, higher immunophenoscores (IPSs), lower mismatch repair protein expression, higher microsatellite instability (MSI), and a higher tumor mutation burden (TMB). Furthermore, the level of expression of prognostic lncRNAs was significantly related to the sensitivity of cancer cells to anti-tumor drugs.Conclusion: A novel signature composed of five prognostic lncRNAs associated with genome instability can be used to predict prognosis, influence immune status, and chemotherapeutic drug sensitivity in EC.