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Objective: This study aimed to explore the role of miRNAs in pathogenesis of endometriosis. Methodology: Endometrial samples from 57 females with endometriosis and 44 non-endometriotic controls were compared for the expression of a selected group of miRNAs. The regulatory function on downstream target was also explored. Results: The expression of miR-93 and miR106a was significantly reduced in endometriotic samples compared to that in non-endometriotic samples. High levels of MMP3 and VEGFA were detected in more than 50% ectopic endometrium tissues. A negative association was found between the expression of miR-93 and the protein levels of MMP3 (Pearson correlation, r=-0.39, P=0.0025) or VEGFA (Pearson correlation, r=-0.37, P=0.0047) in samples from endometriosis patients. Mechanistically, miR-93 targeted MMP3 and VEGFA by directly binding to the 3’UTR of MMP3 and VEGFA mRNAs, and thereby inhibited the proliferation, migration and invasive capability of endometrial stromal cells (ESCs). Conclusion: The finding of this study suggests that deregulation of miR-93 contribute to endometriosis by up-regulation of MMP3 and VEGFA and thus provide potential therapeutic targets for the treatment of endometriosis.
Endometriosis, microRNA, proliferation, migration, invasion
Down regulation of MiR-93 contributes to endometriosis through targeting MMP3 and VEGFA
Xuan Lv, Pei Chen, Wei Liu
Gastrointestinal stromal tumor (GIST) is known for its wide variability in biological behaviors and it is difficult to predict its malignant potential. The aim of this study is to explore the characteristics and prognostic factors of GIST.
Clinical and pathological data of 497 GIST patients in our center between 1997 and 2012 were reviewed.
Patients were categorized into very low-, low-, intermediate- and high-risk groups according to modified National Institutes of Health (NIH) consensus classification system. Among the 401 patients untreated with imatinib mesylate (IM), 5-year overall survival (OS) in very low-, low-, intermediate- and high-risk groups was 100%, 100%, 89.6% and 65.9%; and 5-year relapse-free survival (RFS) was 100%, 98.1%, 90.9% and 44.5%, respectively. Univariate analysis revealed that sex, tumor size, mitotic rate, risk grade, CD34 expression, and adjacent involvement were predictors of OS or RFS. COX hazard proportional model (Forward LR) showed that large tumor size, high mitotic rate, and high risk grade were independent risk factors to OS, whereas high mitotic rate, high risk grade and adjacent organ involvement were independent risk factors to RFS. The intermediate-high risk patients who received IM adjuvant therapy (n = 87) had better 5-year OS and RFS than those who did not (n = 188) (94.9% vs. 72.1; 82.3% vs. 56.3%, respectively). Similarly, advanced GIST patients underwent IM therapy (n = 45) had better 3-year OS and 1-year progression-free survival (PFS) than those who didn’t (n = 42) (75.6% vs. 6.8%; 87.6% vs. 12.4%, respectively).
Very low- and low-risk GISTs can be treated with surgery alone. Large tumor size, high mitotic rate, high risk grade, and adjacent organ involvement contribute to the poor outcome. IM therapy significantly improves the survival of intermediate-high risk or advanced GIST patients.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2482-14-93) contains supplementary material, which is available to authorized users.
Gastrointestinal stromal tumor, Survival, Imatinib
Gastrointestinal stromal tumor: 15-years’ experience in a single center
Ming Wang, Jia Xu, Yun Zhang, Lin Tu, Wei-Qing Qiu, Chao-Jie Wang, Yan-Ying Shen, Qiang Liu, Hui Cao
Juvenile myelomonocytic leukemia (JMML) is a heterogeneous childhood leukemia. The management of patients with JMML requires accurate assessment of genetic and clinical features to help in patient risk stratification. This study aimed to investigate the association between genomic alterations and prognosis in children with JMML. Genomic DNA was extracted from a total of 93 patients with JMML for targeted sequencing. Univariable and multivariable analysis were used to evaluate the correlation between gene mutations and prognosis of the patients. Patients with PTPN11 mutation exhibited significantly lower event-free survival (EFS) compared with non-PTPN11 mutations (P = 0.005). Patients without or with one somatic alteration at diagnosis showed significantly better prognosis in comparison with those with more than two alterations (P = 0.009). PTPN11 mutation with additional alterations showed significantly the poorest outcome in comparison with those with only one non-PTPN11 mutation, only one PTPN11 mutation, and combined mutations without PTPN11, respectively (P < 0.0001). Conclusion: Both PTPN11 mutation and the number of somatic alterations detected at diagnosis are likely to be the major determinant of outcome in JMML. The subgroup of patients with PTPN11 mutation showed the shortest survival which was even worsened when a secondary mutation was present.
Gene mutation, Juvenile myelomonocytic leukemia, PTPN11, Secondary mutation
PTPN11 mutation with additional somatic alteration indicates unfavorable outcome in juvenile myelomonocytic leukemia: a retrospective clinical study from a single center
Yan Miao, Benshang Li, Lixia Ding, Hua Zhu, Changying Luo, Jianmin Wang, Chengjuan Luo, Jing Chen