A novel necroptosis-related lncRNA signature for predicting prognosis and anti-cancer treatment response in endometrial cancer

Abstract

BackgroundNecroptosis, a form of programmed cell death, underlies tumorigenesis and the progression of cancers. Anti-cancer strategies targeting necroptosis have increasingly been shown to present a potential cancer therapy. However, the predictive utility and anticancer sensitivity value of necroptosis-related lncRNAs (NRLs) for endometrial cancer (EC) are currently unknown.MethodsEC patient gene expression profiles and the corresponding clinical information collected from The Cancer Genome Atlas were used to identify NRLs that constituted a predictive signature for EC. The functional pathways, immune status, clinicopathological correlation, and anticancer drug sensitivity of the patients relative to the NRLs signatures were analyzed.ResultsA signature composed of 7 NRLs (AC019080.5, BOLA3-AS1, AC022144.1, AP000345.2, LEF1-AS1, AC010503.4, and RPARP-AS1) was identified. The high-risk patient group with this signature exhibited a poorer prognosis and lower survival rate than low-risk group lacking this signature. This necroptosis-related lncRNA signature had a higher predictive accuracy compared with other clinicopathological variables (area under the receiver operating characteristic curve of the risk score: 0.717). Additionally, when patients were stratified based on other clinicopathological variables, the overall survival was significantly shorter in the high-risk versus low-risk group across all cohorts. Gene set enrichment analysis (GSEA) revealed that immune- and tumor-related signaling pathways and biological processes were enriched in the high-risk group compared to the low-risk group. Single-sample gene set enrichment analysis (ssGSEA) additionally showed that the resulting risk score was strongly correlated with EC patient immune status. Finally, patients with high-risk scores were more sensitive to the anti-cancer drugs such as Docetaxel, Mitomycin.C, Vinblastine, AZD.2281 (olaparib), AZD6244, and PD.0332991 (Palbociclib).ConclusionThese findings reveal a novel necroptosis-related lncRNA signature for predicting EC patient prognosis and shed new light on anticancer therapy strategies for EC.

lncRNA XIST/miR‑129‑2‑3p axis targets CCP110 to regulate the proliferation, invasion and migration of endometrial cancer cells

“…Long non-coding RNAs (lncRNAs) are defined as RNA molecules that exceed 200 nucleotides and are not translated into proteins (32). These RNAs can regulate the expression of target genes by participating in epigenetic, transcriptional and post-transcriptional pathways, and are related to the proliferation, migration and invasion of various tumors, such as female reproductive or gynecological cancers (33,34).…”

Development and validation of a novel DNA damage repair-related long non-coding RNA signature in predicting prognosis, immunity, and drug sensitivity in uterine corpus endometrial carcinoma

“…Previous studies have revealed that lncRNAs are dysregulated and play diverse roles in the carcinogenesis, metastasis, and therapeutic resistance of UCEC [10] . Several lncRNA-related prognostic models have been developed to aid the clinical management of UCEC [11] , [12] , [13] . Nevertheless, the role of DDR-related lncRNAs (DRLs) in UCEC has not been comprehensively explored.…”

Development and verification of a newly established cuproptosis-associated lncRNA model for predicting overall survival in uterine corpus endometrial carcinoma

“…Long non-coding RNAs (lncRNAs) are composed of more than 200 nucleotides, shown to be increasingly involved in various malignant cancer progression ( 6 ). LncRNAs were found to be involved in UCEC cell proliferation, invasion, and metabolic changes by targeting miRNAs axis ( 7 ). Experimental study has suggested that LINC00958 regulates the function of IGF2BP3, thus participating in the tumorigenesis and progression of UCEC ( 8 ).…”