Identification of key molecules in miRNA-mRNA regulatory network associated with high-grade serous ovarian cancer recurrence using bioinformatic analysis / 南方医科大学学报

OBJECTIVE@#To investigate the correlation of the potential functional microRNA (miRNA)-mRNA regulatory network with recurrence of high-grade serous ovarian carcinoma (HGSOC) and its biological significance.@*METHODS@#This study was performed based on the data of 354 patients with HGSOC from the Cancer Genome Atlas database. In these patients, HGSOC was divided into different subtypes based on the pathways identified by GO analysis, and the correlations of the subtypes with HGSOC recurrence and differentially expressed miRNAs and mRNAs were assessed. Two relapse-related datasets were identified using the Gene Set Enrichment (GSE) database, from which the differentially expressed miRNAs were identified by intersection with the TCGA data. The target genes of these miRNAs were predicted using miRWalk 2.0 database, and these common differentially expressed miRNAs and mRNAs were used to construct the key miRNA-mRNA network associated with HGSOC recurrence. The expression of miR-506-3p and SNAI2 in two ovarian cancer cell lines was detected using RT-qPCR and Western blotting, and their targeted binding was verified using a double luciferase assay. The effect of miR-506-3p expression modulation on ovarian cancer cell migration was detected using scratch assay and Transwell assay.@*RESULTS@#We screened 303 GO terms of HGSOC-related pathways and identified two HGSOC subtypes (C1 and C2). The subtype C1 was associated with a significantly higher recurrence rate than C2. The differentially expressed genes between C1 and C2 subtypes were mainly enriched in epithelial-mesenchymal transition (EMT). Five miRNAs were identified as potential regulators of EMT, and a total of 41 target genes were found to be involved in the differential expressions of EMT pathway between C1 and C2 subtypes. The key miRNA-mRNA network associated with HGSOC recurrence was constructed based on these 5 miRNAs and 41 mRNAs. MiR-506-3p was confirmed to bind to SNAI2, and up-regulation of miR-506-3p significantly inhibited SNAI2 expression and reduced migration and invasion of SKOV3 and CAOV3 cells (P < 0.05), while miR-506-3p knockdown produced the opposite effects (P < 0.05).@*CONCLUSION@#MiR-506-3p and SNAI2 are the key molecules associated with HGSOC recurrence. MiR-506-3p may affect EMT of ovarian cancer cells by regulating cell migration and invasion via SNAI2, and its expression level has predictive value for HGSOC recurrence.

Carcinoma seroso de ovario. Serie de 14 casos y revisión de la bibliografía / Serous ovarian cancer. Report of 14 cases and review of the bibliography

Resumen OBJETIVO: Describir las características epidemiológicas, clínicas, de laboratorio, de tratamiento médico-quirúrgico y patología, en una serie de 14 pacientes con carcinoma seroso de ovario atendidas en un hospital de alta complejidad y revisión de la bibliografía con el fin de actualizar los conceptos. MATERIALES Y MÉTODOS: Estudio de serie de casos retrospectivo y descriptivo de pacientes con cáncer de ovario seroso confirmado por patología. Las pacientes se estudiaron en un hospital general de alta complejidad entre 2013 y 2016. Variables de estudio: epidemiológicas, clínicas, de laboratorio, del tratamiento médico quirúrgico, comorbilidades y patología. Revisión narrativa de la bibliografía correspondiente a la información relacionada con las variables evaluadas. RESULTADOS: Se diagnosticaron 14 mujeres, de 50 a 80 años; 3 casos con antecedente de histerectomía y 1 de salpingoclasia. Diagnóstico histológico: 10 con tumor seroso de alto grado, 2 moderadamente diferenciado, 1 seroso de bajo grado y otro no clasificado. Procedimientos quirúrgicos: histerectomía, salpingooforectomía bilateral, linfadenectomía, omentectomía en 8 casos. Clasificación en estadios: IV en 6, 3 IIIB, 2 IC, 1 IIIC y una 1 IB. Tratamiento: 10 mujeres con carboplatino y paclitaxel. Revisión de 2227 artículos encontrados, 41 seleccionados. CONCLUSIONES: El carcinoma seroso de ovario se clasifica, actualmente, en bajo y alto grado (más frecuente y agresivo). Este tipo fue el más frecuente, los factores de riesgo encontrados, por el número reducido de pacientes, no permiten emitir conclusiones.

Abstract OBJECTIVE: To describe the epidemiological, clinical, laboratory, surgical medical management and pathology characteristics in a series of 14 patients with serous ovarian carcinoma in a highly complex hospital and review of the literature in order to update the concepts. MATERIALS AND METHODS: Retrospective and descriptive case series study of a patient with serous ovarian cancer confirmed by pathology. The patients were studied in a highly complex general hospital between 2013 and 2016. Study variables: Epidemiological, clinical, laboratory surgical medical treatment, comorbidities, and pathology. Narrative review of the bibliography corresponding to information related to the evaluated variables. RESULTS: Fourteen women between the ages of 50 and 80 were diagnosed, 3 with a history of hysterectomy and 1 with tubal ligation. Histological diagnosis: 10 with high-grade serous tumor, 2 moderately differentiated, 1 low-grade serous and one not classified. Surgical procedures: hysterectomy, bilateral salpinges-oophorectomy, lymphadenectomy, omentectomy in 8 cases. They classified into states: IV in 6, 3 IIIB, 2 IC, 1 IIIC and 1 IB. Treatment 10 women with carboplatin and paclitaxel. Review 2227 articles were found, 41 sectioned. CONCLUSIONS: Serous ovarian carcinoma is currently classified as low and high grade (more frequent and aggressive). This type was the most frequent, the risk factors found by the reduced number do not allow conclusions to be drawn.

The relationship of serum levels of FSH, LH and PRL and clinicopathological features and prognosis in patients with serous ovarian cancer / 天津医药

Objective To investigate the relationship between serum follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and clinicopathological features and prognosis of serous ovarian cancer retrospectively. Methods A total of 73 patients with serous ovarian cancer treated in the Department of Obstetrics and Gynecology of Tianjin Medical University General Hospital from January 2000 to December 2015 were included in this study. The relationship between serum FSH, LH, PRL and clinicopathological features was analyzed by Mann-Whitney U method. Kaplan-Meier (K-M) method was used to analyze survival rates of patients with different clinical features. Multivariate Cox proportional hazards regression analysis was used to analyze prognostic factors of serous ovarian cancer patients. Results The mean concentrations of serum FSH and LH were significantly higher in the>50 year-old group than those in the0.05). There was no significant correlation between serum PRL concentration and clinicopathological features (P>0.05). Analysis results showed that poor prognosis of patients was related with high serum levels of FSH (>40.13 IU/L), PRL (>14.96 μg/L) and FIGO stage (Ⅲ+Ⅳ) (P0.05). COX regression analysis showed that the serum PRL>14.96 μg/L was risk factor for prognosis of serous ovarian cancer [HR(95%CI): 3.530(1.180-10.557),P=0.024]. Conclusion The serum levels of FSH and LH are significantly increased in postmenopausal women than those in menopause women. The serum level of PRL is correlated with the prognosis of serous ovarian cancer.

Expression of Beclin1, p62 and Atg5 in tissue of serous ovarian cancer and its significance / 中华内分泌外科杂志

Objective To investigate the expression of Beclin1,p62 and Atg5 in serous ovarian cancer and its clinical significance.Methods The expression of Beclin1,p62 and Atg5 was detected in 50 serous ovarian cancer tissues by immunohistochemical method,and the relationship between their expression levels and the clinical parameters of serous ovarian cancer patients were analyzed.Results The expression of Beclin1 and Atg5 in serous ovarian cancer tissue was significantly lower than that in normal ovarian tissue,but p62 was significantly higher than that in normal ovarian tissue,and the difference had statistically significance (P＜0.05).The expression of Beclin1 and Atg5 were correlated with degree of cell differentiation and clinical stage (P＜0.05),while the expression of p62 was associated with clinical stages and lymph node metastasis (P＜0.05).Conclusions The abnormal expression of Beclin1,p62,Atg5 in serous ovarian cancer,which can lead to reduced autophagy body formation and autophagy activity,may be involved in the occurrence and development of serous ovarian cancer.

Preoperative plasmic D-dimer levels predict the response to first-line chemotherapy and the prognosis of serous ovarian cancer / 中国肿瘤临床

Objective:To investigate the correlation of plasma D-dimer levels with the response to first-line chemotherapy and the prognosis of patients with serous ovarian cancer (SOC). Methods:The preoperative plasmic D-dimer levels of 143 patients with prima-ry SOC were retrospectively evaluated. The patients were admitted to Tianjin Medical University Cancer Institute and Hospital between January 2008 and May 2010. The patients were divided into two groups on the basis of plasmic D-dimer levels. Group A consisted of 100 patients with a normal plasmic D-dimer level of≤0.3 mg/L. Group B included 43 patients with an increased plasmic D-dimer level of>0.3 mg/L. The correlations of the different plasmic D-dimer levels with clinicopathological features, therapeutic effects, and surviv-al outcomes were further analyzed. Results:The plasmic D-dimer levels were positively correlated with the staging of the Federation of International Gynecology and Obstetrics, residual tumor size, presence of malignant ascites, preoperative serum CA125 level, and neo-adjuvant chemotherapy. Group B exhibited a significantly lower (P<0.001) complete response (CR) rate of 34.88%(15/43) than group A, which yielded a CR rate of 73.00%(73/100). The progression-free survival and overall survival rates of group B were significantly lower than those of group A (25.58%vs. 50.00%and 32.56%vs. 65.00%;P<0.05). Multivariate analysis revealed that the plasmic D-di-mer level is an independent prognostic factor associated with unfavorable prognosis. Conclusion:Increased preoperative plasmic D-di-mer levels may be a potential biomarker of weak responses to first-line chemotherapy and poor clinical outcomes in patients with SOC.

Expression and clinical significance of Claudin-4 in human serous ovarian cancer / 中华内分泌外科杂志

Objective To investigate the expression and clinical significance of Claudin-4 in human se-rous ovarian cancer.Methods 43 cases of serous ovarian cancer from Oct.2008 to May 2014 were studied.Re-al-time quantitative PCR( qRT-PCR) was applied to detect mRNA expression of Claudin-4 in serous ovarian cancer ( n=43 ) in comparison to the corresponding tumor-adjacent tissues.The protein expression of Claudin-4 was measured by immunohistochemistry( IHC) .Results mRNA and protein expression level of Claudin-4 was signif-icantly higher in serous ovarian cancer tissues than in adjacent normal tissues(P<0.05).The high expression of Claudin-4 protein was also associated with large tumor size, lymphatic metastasis, and advanced TNM stage( P<0.05 ) .Conclusions The expression of Claudin-4 is significantly higher in serous ovarian cancer tissues than in the adjacent normal tissues, and it is associated with clinicopathological features.Claudin-4 may become a new marker in early diagnosis and biological target therapy.

El cáncer de ovario, el asalto del homicida invisible / Ovarian cancer, the assault by an invisible murderer

El cáncer de ovario se origina de 3 tipos de células: células epiteliales, células germinales y células del estroma. Aproximadamente el 90% de los casos de cáncer de ovario son del tipo epitelial, que es la forma más frecuente de los 3 tipos histológicos y desafortunadamente una de las principales causas de muerte por cáncer del aparato reproductor femenino, al ser una enfermedad con sintomatología insidiosa e inespecífica, que lamentablemente tiene una mortalidad extremadamente alta. La incidencia de este tipo de estirpe aumenta con la edad, y a diferencia del de las células germinales y del estroma, son raros antes de los 40 años. Es importante saber que tanto en México como a nivel global, la variedad en incidencia del subtipo histológico del cáncer epitelial de ovario se da en las siguientes proporciones: seroso (60-80%), mucinoso (10-25%), endometrioide (8-20%), de células claras (5%), tumor de Brenner (< 1%) e indiferenciado. Esto nos muestra que el cáncer de ovario epitelial seroso es el más frecuente en el mundo, y por lo tanto, el que más asecha a las mujeres.

Ovarian cancer develops from three kinds of cells: epithelial cells, germ cells, and stromal cells. About 90% of ovarian cancer is of the epithelial kind, thus being the most frequent of the three histological types and, unfortunately, one of the main causes of death by female reproductive system cancer; due to the insidious and unspecific symptomatology of this disease, which, regrettably, has an extremely high mortality. The incidence of this kind of lineage increases with age and, unlike germ and stromal cancers, it is rare before the fifth decade of life. It is important to know that in Mexico as well as in the rest of the world, that the incidence of the different varieties of the histological subtype of ovarian epithelial cancer is as follows: serous (60-80%), mucinous (10-25%), endometrioid (8-20%), clear cells (5%), Brenner tumor (<1%) and not differentiated. Epithelial-serous ovarian cancer is the most frequent in the world; therefore, the one we fear hunts most of our women.

HE4 expression in serous ovarian cancer tissues and its relationship with clinicopathological features / 实用肿瘤学杂志

Objective To investigate the expression level of human epididymis protein 4 ( HE4 ) in se-rous ovarian cancer tissues and its relationship with clinicopathological features .Methods The expression level of HE4 in 140 serous ovarian cancer patients and its relationship with clinicopathological features were detected by immunohistochemistry.To compare the correlation between HE4 and CA125, the histological expressionOf CA125 was also detected by IHC .Results the positive expression rate of HE 4 and CA125 in moderately and poorly differentiated serous ovarian cancer tissues were respectively 89.76%and 81.89%;the positive expression rate in well differentiated group were respectively 46.61% and 15.38%,in the advanced stages were 92.44%and 83.19%,in the early stages were 47.62%and 33.33%.the positive expression rate of lymphatic metastasis were 95.65%and 84.35%,without lymphatic metastasis were 40.00%and 36.00%,the positive expression rate of peritoneal implantation were 90.00% and 87.27%, without peritoneal implantation were 70.00% and 33.33%;the positive expression rate of ascites were 89.76% and 79.53%,without ascites were 46.15% and 38.46%.Besides,the positive expression rates of HE4 and CA125 were 86%and 76%,the differences were sta-tistically significant.Both the positive expression in ovarian cancer are correlated positively (P0.05).Conclusion The expression of HE4 in serous ovarian cancer is related with FI-GO stages,the degree of tumor differentiation ,lymph node metastasis and ascites .

Differences of EDR Chemoresistance Assay and Prognosis between Recurrent Micropapillary Serous Ovarian Carcinoma and Serous Ovarian Carcinoma / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to identify chemoresistance and prognosis differences between recurrent micropapillary serous ovarian carcinoma (MPSC) and serous ovarian carcinoma. METHODS: The Extreme drug resistance (EDR) assay was performed in 13 recurrent micropapillary serous ovarian carcinoma and 56 recurrent serous ovarian carcinoma. RESULTS: Mean age of MPSC and Serous ovarian cancer were 41.1 and 58.0 respectively (p<0.05). Etoposide and Doxil were the two least resistance chemotherapeutic agents to recurrent MPSC but the most resistance agents to recurrent serous ovarian cancer. Taxol and cisplatin were the two most resistance agents to MPSC. The mean follow up was 42 months (range 1-173) The five-year overall survival rate of MPSC and serous ovarian carcinoma were 71.6% and 33.9% respectively. The mean survival were 136 months in MPSC compared with 72 months in serous ovarian carcinoma (p<0.035). CONCLUSION: In this retrospective analysis, MPSC showed very different in EDR results and favorable prognosis compare to serous ovarian carcinoma.