JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE) ›› 2021, Vol. 41 ›› Issue (9): 1207-1214.doi: 10.3969/j.issn.1674-8115.2021.09.011

• Basic research • Previous Articles    

Expression and clinical significance of DNA polymerase θ in endometrial cancer

Bei-bei XUAN1(), Sai-nan GONG2, Jia-li LIU2, Quan QUAN2, Yu MENG2, Xiao-ling MU1()   

  1. 1.The First Clinical College, Chongqing Medical University, Chongqing 400016, China
    2.Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
  • Received:2021-03-26 Online:2021-08-24 Published:2021-08-24
  • Contact: Xiao-ling MU E-mail:xuanbeibei0806@163.com;mxl@hospital.cqmu.edu.cn
  • Supported by:
    Natural Science Foundation of Chongqing(cstc2017shmsA130034)

Abstract: Objective

·To explore and verify the differential expression of DNA polymerase θ (POLQ) in endometrial cancer (EC) and normal endometrial tissues, and analyze its relationship with clinical characteristics of EC patients and its value in prognostic judgement.

Methods

·Gene Expression Profiling Interactive Analysis (GEPIA) website was used to retrieve the expression of POLQ in cancer tissues and normal tissues in various parts of the human body. The POLQ gene expression profile and the clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. The gene expression matrix was obtained by Strawberry Perl software. The differences in the POLQ expression between EC and paracancerous tissues and the relationship between the POLQ expression and the clinical characteristics were analyzed by R software. Gene Set Enrichment Analysis (GSEA) was used to reveal the signaling pathways in which POLQ participated in EC. The clinical information of 127 patients diagnosed as having EC by histopathology, who underwent surgery in the First Affiliated Hospital of Chongqing Medical University from March 2011 to December 2014, were collected to analyze the differences in the POLQ expression among patients with different clinical characteristics. Immunohistochemical staining was performed on paraffin sections of tumor tissues from these patients to determine the expression of POLQ in the tumor tissues, and normal endometrium tissues from 22 patients with uterine fibroids were used as controls. Kaplan?Meier method and multivariate Cox regression model were used to analyze the correlation between POLQ expression and prognosis.

Results

·It was found that POLQ expression was relatively lower in testicular germ cell tumor, but increased in most cancers through GEPIA website. The expression of POLQ in EC tissues was significantly higher than that in paracancerous tissues in the TCGA database (P=0.000), and POLQ was more expressed in the patients with the age of 60 years and above and in the highly graded patients (both P<0.05). Overall survival of the patients with high expression of POLQ was shorter (P=0.000). The results of GSEA showed that POLQ gene was mainly enriched in the base resection repair pathway, homologous recombination pathway, P53 pathway, etc. The proportions of POLQ scores ≥1 and ≥5 in the normal endometrial paraffin sections were significantly lower than those in the EC tissues (both P<0.05). The proportion of POLQ score ≥5 showed statistically significant difference among the patients with different tumor stages or different conditions of lymph node metastasis (both P=0.038). The disease-free survival and overall survival of the patients with high POLQ expression were significantly shorter than those of the patients with low POLQ expression (both P<0.05). Multivariate Cox analysis showed that POLQ score could be used as an independent prognostic indicator.

Conclusion

·Compared with normal endometrium, the expression of POLQ significantly increase in EC tissues, especially in patients with advanced stage and lymph node metastasis, and high expression of POLQ is an independent predictor of poor prognosis in EC patients.

Key words: endometrial cancer (EC), DNA polymerase θ (POLQ), bioinformatics, The Cancer Genome Atlas (TCGA), prognosis

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