Endometriosis And Related Research Of Cancer

Objective:Male mice bone marrow mesenchymal stem cells (BMSCs) have been demonstrated to differentiate into female endometrial epithelial cells (EECs) in vivo. Our group has demonstrated that BMSCs can differentiate in the direction of EECs in condition of co-culture with endometrial stromal cells in vitro. Here we tend to obtain information in the process of differentiation of BMSCs into EEC by isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis and discern some potential pathways in the process.Methods:A0.4μm pore size indirect co-culture system was established with female mice endometrial stromal cells (EStCs) restricted in Transwell chamber into BMSCs. After indirect co-culture for several days, BMSCs were revealed to progressively differentiate towards epithelial like cells in vitro. Then five groups were divided according to different co-culture days with EECs and BMSCs single culture groups as control. Differential candidate proteins were analysed through proteomic approach of based iTRAQ quantitative differential LC-MS/MS. Four proteins were verified by Western blot. Gene ontology (GO) analysis and pathway analysis were applied.Results:A total number of208proteins were identified,100of which proteins were differentially expressed with1.2-fold difference, with52up-regulated and48proteins down-regulated. Four proteins verified by Western blot were in general accordance with the results of iTRAQ proteomics. Gene ontology analysis of differential proteins revealed that cellular morphogenesis, motility, adhesion and development of differentiated cells are based on the metabolic process. Ingenuity IPA software analysis demonstrated differential proteins such as Nes, Sod2、Krt8、HSP90、 Anxal play a potential important role in promoting BMSCs to differentiate into EEC by directly and indirectly regulating signaling pathway including NF-κB, MAPK/ERK and P13K/Akt etc.Conclusion:Our study demonstrated the detailed alteration of proteins and signaling pathways during mice BMSCs differentiating into EECs in vitro. More mature autologous EECs could be induced from BMSCs by targetting these important proteins and signaling pathways, which was of potential clinical significance in providing new treatment for Asherman syndrome and endometriosis. Choriocarcinoma is a kind of malignant gestational trophoblastic neoplasia with low incidence. The incidence of choriocarcinoma is estimated to be0.133per100,000woman-years.[l] Most choriocarcinoma lesions located in uterus, however, there were extremely few primary lesions locating in fallopian tubes, cervix or broad ligment etc. The etiology of choriocarcinoma is still unkown to date. Persisting pregnancy of unknown location means women have a plateau or increase in serial serum HCG concentrationsless than500mlU/mL or less than2,000mIU/mL, but no evidence of intrauterine or ectopic pregancy can be found by transvaginal sonography.[2-4] In this article, we present information concerning a rare ectopic choriocarcinoma characterized by invisible primary lesions and low levels of serum human chorionic gonadotropin (hCG) that masqueraded as a persisting pregnancy of unknown location (PPUL). Genomic DNA was extracted from peripheral blood leukocytes of the patient. All ERBB2and P53coding exons were amplified by polymerase chain reaction and subjected to automatic DNA sequencing. In TP53, a SNP rs1042522in codon72(C/G at position119in exon4) was identified. On this basis, a study of SNP rs1042522and susceptiblity of choriocarcinoma was performed.In the first part, we reported the the rare ectopic choriocarcinoma characterized by invisible primary lesions and low levels of serum HCG that masqueraded as a PPUL and the DNA sequencing results of all ERBB2and P53coding exons. No evidence of intrauterine or ectopic pregancy had been found by transvaginal sonography and serum HCG still increased in case of MTX therapy twice. TV assisted laparoscopy, uterine curretage and pathology examination provided no evidence of lesion. It was not until the chest X-ray revealed a nodule in the left lower lobe that we considered the possibility of choriocarcinoma. Pelvic, abdominal and cranial MRI were used to additionally detect a primary left adnexal lesion and a metastatic nodule of choriocarcinoma in the left lower lobe. To our knowledge, this case was the first case of ectopic choriocarcinoma masquerading as PPUL in which the primary and metastatic lesions were timely treated by a combination of chemotherapy and surgery before systemic metastasis. The results of DNA sequencing showed a heterozygous synonymous mutation in codon793(G>A at position116in exon20) in ERBB2and the protein codon did not change. In TP53, a SNP rs1042522in codon72(C/G at position119in exon4) was identified. TP53rs1042522with probablepathogenic allele in Reference SNP Cluster Report, so we hypothesized that rs1042522C/G heterozygosity might be the genetic basis of choriocarcinoma susceptibility.In the second part, we further performed the study of rs1042522and susceptibility of choriocarcinoma on previous basis. Genomic DNA were extracted from peripheral blood leukocytes of23choriocarcinoma patients and84healthy women as control to sequence rs1042522. The chosen population fit Hardy-Weinberg equilibrium. Both the odds ratio (OR) of allele C compared to allele G and the OR of genotype C/C, C/G, C/G+C/C compared to G/G were larger than1, but the differences are of no significance, which suggested rs1042522might not correlate with susceptibility of choriocarcinoma. We presumed the small number of choriocarcinoma patients might affect the statistic analysis. Thus, more patients should be enrolled to explore the rs1042522and susceptibility of choriocarcinoma.In summary, we performed the study of rs1042522and susceptibility of choriocarcinoma on basis of the rare ectopic choriocarcinoma masqueraded as a PPUL. The present result suggested rs1042522might not correlate with susceptibility of choriocarcinoma, but might be affected by the small number of choriocarcinoma patients. Therefore, more patients will be enrolled to continue exploring the study.