| Objective:(1)To study the prognostic factors related to endometrial cancer(EC)in order to guide clinical treatment and follow-up.(2)To investigate the clinicopathological characteristics of patients with EC complicated with diabetes mellitus(DM)or hypertension,and the effect of diabetes or hypertension on the prognosis of patients with endometrial cancer.(3)To study the influence of DM on the gene transcription level and metabolite level of EC,to screen out the genes and metabolites of DM that affect the prognosis of EC,and to analyze related metabolic pathways,so as to provide a basis for the prognosis evaluation of this disease,reduce the mortality rate of patients,and extend the progression-free survival of patients.Method:(1)The clinicopathological data of EC patients admitted to the Department of Gynecologic Oncology,Tianjin Central Hospital of Gynecology and Obstetrics from April 2011 to December 2013 were retrospectively analyzed,and the corresponding follow-up was conducted.Univariate analysis and Cox proportional risk regression model were used to analyze the prognostic factors of EC.(2)The clinicopathological data of patients with EC complicated with diabetes or hypertension were analyzed retrospectively.Univariate analysis and log-rank test were used to compare the difference in prognosis between patients with EC complicated with diabetes or hypertension and EC without comorbidity,and the effect of diabetes or hypertension on the prognosis of patients with endometrial cancer.(3)The transcriptome of EC patients and EC patients with DM were detected and analyzed by transcriptome technology,and the differentially expressed genes in the two groups of EC tissues were screened out.The pathway enrichment analysis was carried out to search for possible prognostic genes,so as to provide guidance for the treatment and prognosis of EC patients.(4)Metabolomics analysis was performed on EC patients without DM and EC patients with DM by liquid chromatography(LC/MS).Then,the data were analyzed and processed to screen out metabolites with differences,and related metabolic pathways were further analyzed by differential metabolites.Results:(1)The 5-year overall survival rate(OS)and 5-year progression-free survival(PFS)in 479 EC patients were 95.2% and 92.5%,respectively.COX proportional risk regression model multivariate analysis showed that age,combined with diabetes,hypertension,surgical pathological staging,histological type,and lymphovascular space invasion were independent prognostic factors for OS and PFS in endometrial cancer.(2)The prognosis of OS and PFS in EC patients with DM and EC patients with hypertension were worse than those in EC patients without DM or hypertension,respectively.The difference was statistically significant(OS: P<0.001,P =0.008;PFS:P<0.001,P =0.002).(P=0.041;P=0.012)(3)In subgroup analysis,OS and PFS of EC with DM were significantly lower than those of EC without DM(P =0.006;P =0.005),aged 60 or older(P =0.011;P =0.025),operative pathological stage I-II(P<0.001;P<0.001),histological grade G3(P=0.000;P =0.000),endometrioid adenocarcinoma((P=0.041;P=0.012)).In addition,there were statistically significant differences in PFS between histological grade G2(P =0.001)and non-intrauterine appearance adenocarcinoma(P=0.001).Compared with EC patients with hypertension and EC patients without hypertension,the OS and PFS of the two groups were significantly higher in surgical pathological stage I-II(P=0.001;P<0.001),histological grade G1(P =0.037;P =0.036),G3 grade(P =0.048;P=0.011),intrauterine adenocarcinoma(P=0.043;P=0.024)were statistically significant in all patients;In addition,in non-intrauterine adenocarcinoma(P=0.045),there was a statistically significant difference in PFS between the two groups.These results suggest that diabetes mellitus and hypertension have different effects on prognosis in the stratification of clinicopathological factors in EC patients.(4)Transcriptome sequencing analysis was performed in the two groups of tumor tissues,and 275 up-regulated and 490 down-regulated differential genes were obtained.The results showed that the GO functional annotation enrichment analysis showed that in the genes regulating biological processes,the differential genes are mainly concentrated in signal transduction,promoting the development of multicellular organisms,positive regulation of transcription by RNA polymerase II,and cell differentiation.The upgrade gene enrichment pathway was mainly in secretion of bile acid,protein digestion and absorption,cell adhesion molecules,endocrine and other system of regulating calcium absorption,pathway in the tumor,c AMP signal pathway,ABC transporters,the absorption of carbohydrate metabolism,PI3K-AKT signaling pathways,neural activity organization ligand receptor interaction,etc.Most of these pathways were involved in energy metabolism in tumors.The differential gene GPC4 was screened out as a possible prognostic factor of diabetes affecting endometrial cancer,and its specific mechanism needs further study.(5)Metabolomics was used to detect the differences in metabolites and metabolic pathways between the two groups,and a total of 176 differential metabolites were detected,mainly including carboxylic acids and derivatives,glycerolipids,lipids,and pyrimidines.The metabolic pathways with significant differences were mainly the central carbon metabolism,protein digestion and absorption,amino acid biosynthesis and amino acyl t RNA biosynthesis of tumor.Compared with EC without DM group,most of the differential metabolites in EC with DM were significantly up-regulated,and corresponding metabolic pathways were found.The up-regulation of these metabolic pathways can better promote the proliferation,metastasis and invasion of tumors,promote the occurrence and development of tumors,and thus affect the prognosis.This suggests that diabetes may affect the prognostic factors of endometrial cancer.Conclusion:(1)Age,diabetes mellitus,hypertension,surgical pathological stage,histological type and vascular emboli were independent prognostic factors for OS and PFS in endometrial cancer.(2)Patients with EC complicated with DM and patients with EC complicated with hypertension had statistically significant differences in OS and PFS compared with those without DM or hypertension.The former two patients had poor prognosis.(3)Transcriptome and metabonomics analysis showed that diabetes may be a prognostic factor for endometrial cancer. |
PDF Full Text Request