Journal of Jilin University(Medicine Edition) ›› 2021, Vol. 47 ›› Issue (2): 438-452.doi: 10.13481/j.1671-587X.20210225

• Research in clinical medicine • Previous Articles     Next Articles

Bioinformatics analysis based on effect of expression levels of m6A regulators on immune infiltration and prognosis of uterine corpus endometrial carcinoma

Lan ZHENG1,2,Songzhe PIAO3,Ran XU1,Xinyue WANG1,Yixuan WANG1,Zhenhua LIN1(),Yang YANG1()   

  1. 1.Department of Pathology,Key Laboratory of Gynecologic Tumor Bioinformatics,Jilin Provincial Science and Technology Department,College of Medical Sciences,Yanbian University,Yanji 133002,China
    2.Department of Obstetrics and Gynecology,Affiliated Taizhou Hospital,Wenzhou Medical University,Linhai 317005,China
    3.Department of Urology,Affiliated Taizhou Hospital,Wenzhou Medical University,Linhai 317005,China
  • Received:2020-10-14 Online:2021-03-28 Published:2021-03-25
  • Contact: Zhenhua LIN,Yang YANG E-mail:zhlin720@ybu.edu.cn;yangyang@ybu.edu.cn

Abstract: Objective

To analyze the expression levels of 20 m6A-related genes in uterine corpus endometrial carcinoma (UCEC) tissue with the bioinformatics methods data and to screen the hub genes related to prognosis, and to explore the correlations between the expression levels of hub genes and the immune infiltration degrees in UCEC.

Methods

The transcriptome sequencing, clinicopathological and survival data of 547 UCEC and 35 normal controls were obtained from The Cancer Genome Atlas (TCGA) database. The GSE17025 datasets that contained 81 samples of UCEC and 12 samples of adjacent cancer tissue were downloaded from Gene Expression Omnibus (GEO) database. Using the GEO2R online analysis tools and R software, the differentially expressed genes (DEGs) between UCEC tissue and adjacent normal tissue were identified. Survival analysis and Cox regression were carried out for DEGs. The genes that were significantly associated with overall survival (OS) were identified as the hub genes; protein-protein interaction (PPI) network of 20 m6A regulators and correlation analysis of the DEGs were performed using STRING database and R software, respectively. The correlations between the expression levels of hub genes and the clinicopathological features of UCEC were analyzed using the UALCAN database; the correlations between the target genes and immune infiltration degrees and the markers of immune cells were explored via Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) database. Furthermore, survival analysis based on the expression of target genes was conducted in the related immune cell subgroup using Kaplan-Meier Plotter database.

Results

Most of the 20 m6A regulators were significantly differentially expressed in UCEC tissue compared with the adjacent normal tissue (P<0.05); the IGF2BP3 mRNA was highly expressed in UCEC tissue (P<0.05).High IGF2BP3 expression was correlated with shorter OS (P<0.05). Furthermore, both univariate [hazard ratio (HR)=1.106, 95% condifence interval (CI): 1.019-1.202, P=0.016] and multivariate (HR=1.097, 95% CI: 1.003-1.199,P=0.043) Cox regression analysis results showed that IGF2BP3 could be used as an independent risk factor for OS evaluation. IGF2BP3 mRNA exhibited higher expression in the UCEC tissue of advanced stage and pre-menopause patients and endometrial serous adenocarcinoma tissue (P<0.05). The expression level of IGF2BP3 mRNA was positively associated with the degrees of immune infiltration by CD8+T cells (r=0.126, P<0.05),neutrophils (r=0.324,P<0.01) and dendritic cells (DC)(r=0.120, P<0.05) in UCEC. The expression level of IGF2BP3 mRNA was positively associated with the markers of tumor-associated macrophages(TAMs), macrophages (M1 and M2), helper T cells (Th1, Th2, and Th17) and regulatory T cells (Treg) in UCEC (0.1≤r ≤1,P<0.05). The patients with high expression of IGF2BP3 mRNA had a shorter OS than those with low expression of IGF2BP3 mRNA in the low infiltration subgroup of B cells, Treg cells, and Th2 cells (P<0.05).

Conclusion

The expression level of IGF2BP3 mRNA in UCEC tissue is significantly increased, which promotes the immune infiltration of UCEC and indicates the poor prognosis of UCEC patients. IGF2BP3 could be served as a prognostic molecular biomarker of UCEC and indicate the poor prognosis of UCEC patients, and may become a novel target for cancer therapy.

Key words: endometrial cancer, N6-methyladenosine, immune infiltration, bioinformatics

CLC Number: 

  • R737.33