Immune Infiltrates of m5C RNA Methylation-Related LncRNAs in Uterine Corpus Endometrial Carcinoma

Abstract

Aberrant 5-methylcytidine (m5C) modification plays an essential role in the progression of different cancers. More and more researchers are focusing on developing a lncRNA-based risk model to assess the clinical prognosis of cancer patients. However, the impact of m5C-related lncRNAs on the prognosis of patients with uterine corpus endometrial carcinoma (UCEC), as well as the immune microenvironment of UCEC, remains unclear. Here, we comprehensively analyzed the predictive value of m5C-associated lncRNAs in UCEC and their association with the tumor immune microenvironment, according to the information extracted from the TCGA-UCEC dataset. We identified a total of 32 m5C-associated lncRNAs that were significantly correlated with the prognosis of UCEC patients. Two molecular subtypes were determined by consensus clustering analysis of these 32 m5C-associated prognostic lncRNAs. Further data showed that cluster 1 was associated with poor clinical prognosis, advanced tumor grade, higher PD-L1 expression levels, higher ESTIMATEScore, and higher immuneScore, as well as the immune cell infiltration. Then, 17 m5C-associated lncRNAs with prognostic values were obtained using LASSO regression analysis. And a risk model was constructed based on these 17 lncRNAs. It was revealed that the risk model could be used as an independent factor for UCEC prognosis. In addition, patients with UCEC in the high-risk group had higher tumor grades and immune scores. The risk model based on m5C-related lncRNAs was also closely associated with infiltrating immune cells. In conclusion, our study elucidated the crucial roles of the identified m5C-related lncRNAs in the UCEC patients’ prognoses, as well as in the immune microenvironment in UCEC. The results suggest that the components of risk models based on the m5C-related lncRNAs may serve as important mediators of the immune microenvironment in UCEC.

Shining a spotlight on m6A and the vital role of RNA modification in endometrial cancer: a review

“…These mRNAs regulated cell cycle progression accompanied by immune cell infiltration, which might lead to UCEC progression ( Zhao et al, 2022 ). Likewise, the findings indicated that the constituents of hazard models relying on the lncRNAs associated with m5C, m7G, or m6A could function as significant intermediaries of the immune milieu and promising prognosis biomarkers with therapeutic response in UCEC ( Gu et al, 2022 ; Sun et al, 2022 ; Chen et al, 2023 ; Zhou et al, 2023 ). Wang et al outline new insights into CNVs/SNVs in m6A regulatory genes which were associated with a negative impact on patient survival of EC and ultimately found that three genes, IGF2BP3, KIAA1429, and IGF2BP1 , were effective predictors of EC outcomes ( Wang et al, 2020 ).…”

Emerging role of RNA modification and long noncoding RNA interaction in cancer

“…FOXC2-AS1 acts as an oncogenic lncRNA in an m5c-dependent manner by stabilizing FOXC2 mRNA, which may provide a new therapeutic target for GC [ 185 ]. m5C-related lncRNAs have been found to play important roles in regulating the tumor-immune microenvironment in uterine corpus endometrial carcinoma (UCEC) and BLCA [ 85 , 186 ]. Figures 3 and 5 also summarizes the role of m5C modification in the regulation of tumor-associated lncRNAs.…”

RNA N6-methyladenosine modification in female reproductive biology and pathophysiology

“…In an animal experiment, deletion of the m 5 C methyltransferase Nsun5 resulted in suppression of ovarian function and embryonic development arrest in mice [144]. In several bioinformatics studies on ovarian and endometrial cancers, m 5 C-related genes were closely associated with tumour chemotherapy sensitivity and overall survival [145][146][147]. In addition, abnormal m 5 C modification may be involved in TRDMT1-mediated granulosa cell death, which in turn causes premature ovarian failure [148].…”