The High Expression of RRM2 Can Predict the Malignant Transformation of Endometriosis.

INTRODUCTION: A large number of epidemiological studies have revealed that women with endometriosis (EMS) have a higher risk of developing endometriosis-associated ovarian cancer (EAOC). At present, there are few studies on predicting the malignant transformation of ovarian endometriosis (OE). The purpose of this study is to identify and verify the molecules that may be able to predict the malignant transformation of OE. METHODS: The gene expression profiles of ovarian cancer and OE were downloaded from Gene Expression Omnibus (GEO), and a common hub gene ribonucleotide reductase M2 (RRM2) was identified. A total of 44 patients with EAOC and 44 with OE were enrolled in this study. Immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression of RRM2, while the relationship between RRM2 and Ki-67 was analyzed by IHC co-localization. RESULTS: Bioinformatics analysis showed that the expression of RRM2 was low in EMS and high in ovarian cancer. RRM2 was obviously positively expressed in eutopic endometrium (EU), ectopic endometrium (EC), and cancer tissues of EAOC patients. The IHC signal and mRNA levels of RRM2 were higher in the EC of EAOC patients compared with OE patients (P < 0.01). In addition, there was a correlation between the expression of RRM2 and Ki-67 in EC of EAOC patients (P < 0.01). CONCLUSION: The upregulated expression of RRM2 in the EC of OE patients may indicate malignant transformation. High expression of RRM2 promotes abnormal proliferation of histiocytes. RRM2 can be used as a potential marker of malignant transformation of OE.

Distinct clinical and genetic mutation characteristics in sporadic and Lynch syndrome-associated endometrial cancer in a Chinese population.

BACKGROUND: The diagnosis of Lynch syndrome-associated endometrial cancer patients is significant for early warning of their relatives. The purpose of this study was to provide diagnostic indicators of Lynch syndrome-associated endometrial cancer by screening the differential clinical and genetic characteristics. METHODS: Clinical information and hysterectomy specimens were collected from 377 eligible patients with endometrial cancer. The MLH1 methylation level was detected by an EZ DNA Methylation-Gold Kit. According to the above experimental results, the patients were then divided into sporadic endometrial cancer and suspected Lynch syndrome-associated endometrial cancer groups. A total of 62 samples were randomly selected for whole-exome sequencing. IBM SPSS Statistics 21 was used to compare the clinical data between the sporadic and suspected Lynch syndrome-associated endometrial cancer groups, and the relationship between the specific high-frequency-mutation genes and the clinical data. RESULTS: According to the results of MMR immunohistochemistry and MLH1 methylation, the sporadic endometrial cancer group included 361 patients and the suspected Lynch syndrome-associated endometrial cancer group included 16 patients in this study. In the clinical analysis, the average age of the suspected Lynch syndrome-associated endometrial cancer patients was 45.50 ± 11.50 years, which was significantly younger than the 51.17 ± 10.03 years of the sporadic endometrial cancer patients (P = 0.028). The average BMI of the suspected Lynch syndrome-associated endometrial cancer patients was 23.43 kg/m2 (CI: 20, 30), which was lower than the 26.50 kg/m2 of the sporadic endometrial cancer patients (P = 0.028). Combined with the WES data, MASP2, NADK and RNF223 were identified as three specific mutation sites related to age, FIGO stage and histology. CONCLUSIONS: Compared with the suspected endometrial cancer patients, the Lynch syndrome-associated endometrial cancer patients were younger and less obese. Mutations in MASP2, NADK and RNF223 might be regarded as genetic endometrial cancer features related to clinical characteristics.

Clinicopathological characteristics and prognostic value of POLE mutations in endometrial cancer: A systematic review and meta-analysis.

BACKGROUND: The aim of this meta-analysis was to assess the clinicopathological features and to confirm prognostic value of POLE exonuclease domain mutations (EDM) in endometrial carcinoma patients. METHODS: The PubMed, Web of Science, the data of China National Knowledge Infrastructure, and Wan fang Medical Network were systematically searched for relevant articles without a cut-off date. The keywords for the search were "endometrial cancer," "endometrial carcinoma," "EC," "POLE mutations," "POLE exonuclease domain mutations," "POLE-mutant," "clinical characteristics" "prognostic." Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by using Review manager 5.3 and Stata 14.0 statistical software. RESULTS: Six cohort studies assessing 179 EC patients with POLE EDMs were included. The results indicated a favorable progression-free survival in POLE-mutant patients (HR = 0.32; 95% CI: = [0.09-1.18]). Furthermore, the overall survival was great in patients with POLE-mutant (HR = 0.68; 95% CI = [0.41-1.13]). It was shown that a significantly higher incidence of POLE mutations with Federation of International of Gynecologists and Obstetricians (FIGO) I group compared to FIGO II-IV group (pooled ORs: 0.34, 95% CI: [0.12-0.94], P = .04), POLE-mutant EC was not significantly associated with histology (OR = 0.56,95% CI: 0.29-1.23), tumor grade (OR = 1.22,95% CI:0.85-1.74), lymph-vascular space invasion (OR = 0.40,95% 0.06-2.42), depth of myometrial invasion (OR = 0.70,95% CI: 0.41-1.18), lymph node status (OR = 0.41, 95% 0.04-4.50), and European Society for Medical Oncology risk groups (OR = 0.68,95% CI: 0.37-1.26). CONCLUSION: This meta-analysis has confirmed POLE EDMs may serve as a predictive biomarker of favorable prognosis. Further studies are needed to explore the appropriate clinical utility of POLE EDMs in EC.