Multiomics profile and prognostic gene signature of m6A regulators in uterine corpus endometrial carcinoma

Abstract

Uterine corpus endometrial carcinoma (UCEC) is the most common type of gynecologic malignancy worldwide. Despite advances in the treatments of UCEC, its incidence and mortality rates are still increasing. N6-methyladenosine (m6A) is the most common form of RNA modification and has attracted increasing interest in cancer pathogenesis and progression. Thus, we aimed to identify the landscape of m6A regulators and build a prognostic gene signature in UCEC. In this study, we first analyzed copy number variations (CNVs), single nucleotide variations (SNVs) and gene expression profiles as well as matched clinical information of UCEC patients from The Cancer Genome Atlas (TCGA) database. Next, we determined that CNVs in m6A regulatory genes had a significant negative impact on patient survival. The mRNA expression levels of a total of 16 m6A regulators were significantly correlated with different CNV patterns. Using univariate Cox regression analysis, IGF2BP1, KIAA1429, IGF2BP3, YTHDF3, and IGF2BP2 were found to be closely associated with UCEC patient survival outcomes. Based on the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression models, we built a 3-gene (IGF2BP3, KIAA1429 and IGF2BP1) signature of m6A regulators with prognostic value in UCEC that could effectively predict patient prognosis (log-rank test p-value < 0.0001). In addition, risk scores were significantly different between patients stratified by tumor stage, SNV, and CNV. Multivariate Cox regression analysis suggested that risk score might be an independent prognostic indicator for the overall survival of patients with UCEC (p-value < 0.05). Gene enrichment analysis indicated that high IGF2BP1 gene expression is associated with cytoplasmic stress granules. KIAA1429 gene expression is associated with cellular nucleic acid metabolism. The expression of the IGF2BP3 gene is associated with RNA binding processes. In conclusion, we determined that genetic alterations in m6A regulatory genes could be effective and reliable biomarkers for UCEC prognosis prediction.

Pyroptosis-related lncRNAs are potential biomarkers for predicting prognoses and immune responses in patients with UCEC

“…Uterine corpus endometrial carcinoma (UCEC) is a gynecological malignant disease with high mortality, 1 which came in fourth after breast cancer, rectum, and lung cancer. 2 The incidence rate and mortality of UCEC are continuing to rise.…”

Circadian rhythm-associated clinical relevance and Tumor Microenvironment of Non-small Cell Lung Cancer

“…Then, all patients were into a high or low-risk group according to the median value as a cutoff to separately dichotomize the training sets in LUAD and LUSC, and a low-risk score indicates a superior prognosis for patients. This similar approach has been identified from previous studies [21,22]. Finally, the risk-score signature of prognosis was verified in the testing sets, which integrated from the GEO cohorts (GSE30219, GSE31210, GSE3141, GSE37745, GSE50081, GSE68465).…”

Emerging Roles of m6A RNA Methylation Regulators in Gynecological Cancer

“…Univariate Cox regression analysis showed that IGF2BP1, KIAA1429, IGF2BP3, YTHDF3, and IGF2BP2 were closely related to the survival and prognosis of endometrial cancer patients. Among them, IGF2BP3, KIAA1429, and IGF2BP1 can effectively predict the prognosis of patients (93). In addition, Pang et al found that IGF2BP1 and YTHDF3 had a strong ability to stratify the prognosis of different endometrial cancer patients (94).…”