KEY TAKEAWAYS
- The study aimed to create a novel miRNA profile linked to necroptosis for predicting UCEC patient prognosis.
- The results demonstrated that necroptosis potentially contributes to UCEC development via its interplay with immune responses.
Necroptosis, a recently identified caspase-independent cell death mechanism, is implicated in uterine cancer initiation and progression. MicroRNAs (miRNAs), crucial in uterine corpus endometrial carcinoma (UCEC) development, serve as essential regulators within the necroptotic process.
Qi Zhang and the team conducted the study that aimed to formulate a novel miRNA profile associated with necroptosis for prognostic prediction in UCEC patients.
The RNA sequencing data from the TCGA-UCEC cohort, comprising 534 tumor samples and 33 normal samples, was obtained. Ten miRNAs showing differential expression related to necroptosis were identified. A prediction model for necroptosis-associated miRNAs was then developed using COX regression and nomogram analysis. Clinical and pathological parameters were incorporated to construct a nomogram and assess the model.
Prognosis-related miRNAs were utilized to predict target genes, followed by functional analysis to elucidate potential mechanisms of these targets. Subsequent immune infiltration analysis, using transcriptome data, was conducted to identify immune genes linked to prognosis, and the expression levels of target genes were validated using UCEC tissues.
The study identified 7 up-regulated miRNAs (hsa-miR-577, hsa-miR-7-5p, hsa-miR-210-3p, hsa-miR-210-5p, hsa-miR-200a-5p, hsa-miR-141-3p, hsa-miR-425-5p) and 3 down-regulated miRNAs (hsa-miR-7-2-3p, hsa-miR-383-5p, hsa-miR-29a-3p). The risk signature, derived from univariate and multivariate COX analyses, incorporated two independent prognostic factors and miRNAs (hsa-miR-425-5p, hsa-miR-7-5p) associated with necroptosis.
Nomograms illustrated the prognostic significance of risk level, age, FIGO stage, and histological type. Kaplan-Meier analysis indicated significant differences in overall survival (OS) outcomes linked to hsa-miR-425-5p (P < 0.001) and hsa-miR-7-5p (P = 0.015) expression. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses highlighted the pivotal roles of these miRNAs in tumor development, metastasis, and prognosis. Immune infiltration analysis revealed reduced infiltration of CD8+ T cells, CD8+ T cells, NK cells, and M1 macrophages in normal tissues.
Furthermore, a necroptosis-related immune gene significantly associated with prognosis (THRB) was identified, with western blot and immunohistochemical staining confirming differential expression of THRB in normal endometrial tissues and tumors. The findings underscored the intimate link between necroptosis and UCEC.
The results showed that the two necroptosis-related miRNAs investigated in this study may serve as valuable prognostic markers for UCEC patients and are associated with immune cell infiltration.This implies that necroptosis might contribute to UCEC development by interacting with immune responses. No funding information was available.
Source: https://pubmed.ncbi.nlm.nih.gov/38383747/
Zhang, Q., Luo, Y., Zhang, S. et al. Development of a necroptosis-related prognostic model for uterine corpus endometrial carcinoma. Sci Rep 14, 4257 (2024). https://doi.org/10.1038/s41598-024-54651-3.
