Comprehensive Analysis of Copy Number Variation, Nucleotide Mutation, and Transcription Level of PPAR Pathway-Related Genes in Endometrial Cancer.

Abstract

Endometrial cancer is a common malignant tumor in gynecology, and the prognosis of advanced patients is dismal. Recently, many studies on the peroxisome proliferator-activated receptor pathway have elucidated its crucial involvement in endometrial cancer. Copy number variation (CNA) and nucleotide mutations often occur in tumor tissues, leading to abnormal protein expression and changes in protein structure. We analyzed the exon sequencing data of endometrial cancer patients in the TCGA database and found that somatic changes in PPAR pathway-related genes (PPAR-related-gene) often occur in UCEC patients. Patients with CNA or mutation changes in the exon region of the PPAR-related-gene usually have different prognostic outcomes. Furthermore, we found that the mRNA transcription and protein translation levels of PPAR-related-gene in UCEC are significantly different from that of adjacent tissues/normal uterus. The transcription level of some PPAR-related-gene (DBI, CPT1A, CYP27A1, and ME1) is significantly linked to the prognosis of UCEC patients. We further constructed a prognostic predicting tool called PPAR Risk score, a prognostic prediction tool that is a strong independent risk factor for the overall survival rate of UCEC patients. Comparing to the typical TNM classification system, this tool has higher prediction accuracy. We created a nomogram by combining PPAR Risk score with clinical characteristics of patients in order to increase prediction accuracy and promote clinical use. In summary, our study demonstrated that PPAR-related-gene in UCEC had significant alterations in CNA, nucleotide mutations, and mRNA transcription levels. These findings can provide a fresh perspective for postoperative survival prediction and individualized therapy of UCEC patients.