Expressions of CD44,CD47,and c-met in Ovarian Clear Cell Carcinoma and Their Clinical Significance.

Objective To investigate the expressions of CD44,CD47,and c-met in ovarian clear cell carcinoma (OCCC) tissue and their correlations with clinical variables and prognosis. Methods Immunohistochemical method was used to investigate the expressions of CD44,CD47,and c-met in tissues from 86 OCCC patients and the relationships of their expressions with the clinicopathological factors of OCCC were analyzed. Results The expressions of CD44,CD47,and c-met were significantly high in OCCC tissues (90.7%,91.9%,and 94.2%,respectively). The strong positive expressions of CD44 and CD47 were significantly correlated with advanced International Federation of Gynecology and Obstetrics stages,chemotherapeutic resistance,and poor prognosis (all P<0.05),the strong positive expression of c-met was significantly correlated with chemotherapeutic resistance and poor prognosis (all P<0.05),whereas there was no correlation between the strong positive expressions of CD44,CD47,and c-met and the lymphatic node metastasis. COX survival analysis revealed that advanced International Federation of Gynecology and Obstetrics stages and high expressions of CD44,CD47 and c-met were independent risk factors for poor prognosis (P<0.05). There was a positive correlation between CD44 (or CD47) and c-met and between CD44 and CD47 (the Spearman correlation coefficient rs was 0.783,0.776,and 0.835,respectively,all P<0.01). Conclusions The expressions of CD44,CD47,and c-met increase in OCCC tissues and are correlated with each other. High expressions of CD44,CD47,and c-met are independent factors for poor prognosis.

Expression and significance of CD44, CD47 and c-met in ovarian clear cell carcinoma.

AIMS: The aim of the present study is to investigate the differential expression of CD44, CD47 and c-met in ovarian clear cell carcinoma (OCCC), the correlation in their expression and their relationship with the biological behavior of OCCC. METHODS: We used immunohistochemistry to examine the expression of CD44, CD47 and c-met in OCCC (86 cases) and investigated the effects of the expression and interaction of these molecules on the development of OCCC. RESULTS: CD44, CD47 and c-met expression was significantly high in OCCC. Expression of CD44 and CD47 correlated with patient surgical stage, chemotherapy resistance and prognosis (all p<0.05), and expression of c-met correlated with chemotherapy resistance and prognosis (all p<0.05), but did not correlate with lymph node metastasis (all p>0.05). The surgical stage, CD44, CD47 and c-met expression were independent risk factors for OCCC prognosis (all p<0.05). Patients with low levels of CD44, CD47 and c-met showed better survival than those with high levels (all p<0.05). There was a positive correlation between CD44 (or CD47) and c-met, as well as between CD44 and CD47 (the Spearman correlation coefficient rs was 0.783, 0.776 and 0.835, respectively, all p<0.01). Additionally, pairwise correlation analysis of these three markers shows that the high expression of CD44/CD47, CD44/c-met and CD47/c-met were correlated with patient surgical stage, chemotherapy resistance and prognosis (all p<0.05), but did not correlate with lymph node metastasis (all p>0.05). CONCLUSIONS: Expression of CD44, CD47 and c-met was upregulated in OCCC and pairwise correlation. CD44, CD47 and c-met may have synergistic effects on the development of OCCC and are prognostic factors for ovarian cancer.

Beclin 1 expression in ovarian tissues and its effects on ovarian cancer prognosis.

Beclin 1 is an autophagy-associated protein involved in apoptosis and drug resistance, as well as various malignancies. We investigated the expression of Beclin 1 protein in ovarian epithelial tissues and correlated it with the prognosis of ovarian cancer. Beclin 1 protein expression was determined using immunohistochemistry in 148 patients with ovarian epithelial cancer, 26 with ovarian borderline tumor, 25 with benign ovarian tumor, and 30 with normal ovarian tissue. The relationships between Beclin 1 protein expression and ovarian cancer pathological characteristics were analyzed. The risk factors for ovarian cancer prognosis were analyzed using Cox's regression model. A survival curve was plotted from the follow-up data of 93 patients with ovarian cancer to analyze the effects of Beclin 1 expression on the prognosis of ovarian cancer. The positive rates of Beclin 1 were significantly higher in ovarian epithelial cancer (148) and borderline tumor (26) than in benign ovarian tumor (25) or normal ovarian tissue (30) (all p<0.001). The surgical stage and Beclin 1 expression were both independent risk factors for ovarian cancer prognosis (both p<0.05). Patients with high Beclin 1 levels showed better survival than those with low Beclin 1 levels (p=0.009). Beclin 1 protein is upregulated in ovarian epithelial cancer and is a prognostic factor of ovarian cancer.

Chemoresistance is associated with MUC1 and Lewis y antigen expression in ovarian epithelial cancers.

OBJECTIVE: The aim of this study was to analyze the correlation and clinical significance between the expression of Mucin-1 (MUC1) and the Lewis y antigen with chemoresistance in ovarian epithelial cancers. METHODS: Ovarian cancer patients (n = 92) treated at our hospital from May 2005 to July 2009 were divided, according to their treatment and follow-up outcomes, into a resistant group (n = 37) or sensitive group (n = 55). The expression of MUC1 and Lewis y antigen in ovarian cancer tissues was detected using immunohistochemistry and correlated with chemoresistance. RESULTS: The positive rates of MUC1 and Lewis y antigen in the resistant group were both 91.89%, significantly higher than their positive rates in the sensitive group (65.45% and 69.09%, respectively, and both p < 0.05). MUC1 or Lewis y expression and the pathological stage of the tissue were independent risk factors for chemoresistance (all p < 0.05). CONCLUSION: The increased expression of MUC1 and the Lewis y antigen is a significant risk factor for chemoresistance in patients with ovarian epithelial cancer.

Systematic Analysis of the Clinical Relevance of Cell Division Cycle Associated Family in Endometrial Carcinoma.

Background: Endometrial carcinoma (EC) is the most common cancer of female reproductive system, thus requiring for new effective biomarkers which could predict the onset of EC and worse prognosis. Cell Division Cycle Associated (CDCA) family plays indispensable roles in cell cycle process. However, no study has been focused on the role of CDCAs in EC. Our study aims to investigate the clinical relevance, potential biologic functions and molecular mechanisms of CDCAs in EC. Methods: GEPIA, cBioPortal, GeneMANIA, Networkanalyst, TCGA-UCEC cohort were utilized in this study. Results: NUF2 and CDCA2/3/4/5/7/8 were significantly highly expressed in EC compared with normal tissues. The patients with high NUF2 and CDCA2/3/4/5/8 expression tended to develop to advanced FIGO stages, poor differentiation and worse prognosis(in both OS and RFS analyses) than those with low expression. By contrast, elevated CDCA7 was significantly associated with better prognosis. CBX2 exerted no significant prognostic impact on EC patients. Distinct patterns of the genetic alterations of CDCAs were observed in various histological subtypes of EC. The biological functions of NUF2 and CDCA2/3/4/5/8 were mainly related with the activation of the following pathway: cell cycle, DNA replication, base excision repair, mismatch repair, nucleotide excision repair, cellular senescence and p53 signaling pathway. Conclusions: Our study provides new insight into the onset and progression of EC and proposes NUF2 and CDCA2/3/4/5/8 could act as oncogenes and have shown great diagnostic and prognostic promise in improving EC patient detection and survival prediction with accuracy.

Lewis(y) antigen promotes the progression of epithelial ovarian cancer by stimulating MUC1 expression.

MUC1 is a type I transmembrane glycoprotein and is overexpressed in various epithelial tumor tissues. Some researchers have demonstrated that the glycosylation status of MUC1 can affect MUC1-mediated tumor growth and cell differentiation. In our previous study, we proved that the abilities of cell proliferation, adhesion, invasion and metastasis, and drug resistance were enhanced in ovarian cancer cells stably expressing Lewis(y). Therefore, we hypothesized that Lewis(y) antigen may play a central role in regulating MUC1 expression, and MUC1-mediated cell growth and differentiation may be closely associated with Lewis(y) antigen. This study aimed to examine the correlation between MUC1 expression and Lewis(y) antigen levels in ovarian cancer cell lines and tissue samples. A series of techniques, including RT-qPCR, western blot anlaysis, immunoprecipitation, immunohistochemistry and double-labeling immunofluorescence were applied to detect the expression of Lewis(y) and MUC1. In malignant epithelial ovarian tumors, the positive expression rates of Lewis(y) antigen and MUC1 were 88.33 and 86.67%, respectively, which were markedly higher than those in borderline (60.00 and 53.33%, P<0.05), benign (33.33 and 30%, P<0.01) and normal (0 and 25%, P<0.01) ovarian samples. There was no correlation between the positive expression rates of Lewis(y) or MUC1 and clinicopathological parameters in ovarian cancers (P>0.05). The expression levels of Lewis(y) and MUC1 correlated with the clinical FIGO stage (P<0.05). Both MUC1 and Lewis(y) were highly expressed in ovarian cancer tissues, and their expression levels were positively correlated (P<0.01). In α1,2-fucosyltransferase (α1,2-FT)-transfected cells, the gene and protein expression levels of MUC1 were significantly upregulated compared with the cells that did not overexpress α1,2-FT (P<0.05). The ratio of Lewis(y) immunoprecipitated with MUC1 to total MUC1 increased 1.55-fold in α1,2-FT-overexpressing cells (P<0.05). The overexpression of Lewis(y) resulted in the upregulation of MUC1. On the whole, our data indicate that both MUC1 and Lewis(y) are associated with the occurrence and development of ovarian cancers.

Expression of hMOF in different ovarian tissues and its effects on ovarian cancer prognosis.

Human MOF (hMOF) is a major acetylase of human H4K16 involved in the regulation of physiological and pathological processes. We investigated the expression of hMOF in different ovarian tissues and its correlation with ovarian cancer prognosis. Reverse transcription PCR and western blot analysis were used to detect hMOF mRNA and protein expression, respectively, in different ovarian tissues. Immunohistochemistry was also performed to detect hMOF expression in different ovarian tissues, including ovarian epithelial cancer, borderline tumor, benign tumor and normal ovarian tissues. In addition, the relationships between hMOF expression and clinicopathological ovarian cancer data were analyzed. The Cox proportional-hazards regression model was used to analyze the factors associated with ovarian cancer prognosis. To analyze the effects of hMOF expression on ovarian cancer prognosis, a survival curve was plotted from the follow-up data of 77 patients with ovarian cancer. Compared with normal ovarian tissues, hMOF mRNA and protein expression was significantly decreased in ovarian epithelial cancer tissues. The proportions of high hMOF expression in normal and benign ovarian epithelial tumor tissues, were much higher than those in ovarian epithelial cancer tissues. Furthermore, hMOF protein expression was closely associated with the ovarian cancer stage. The expression of hMOF protein was determined as an independent risk factor influencing ovarian cancer prognosis. Patients with high hMOF levels showed improved survival than those with low hMOF levels. hMOF mRNA and protein expression decreased in ovarian epithelial cancer, thus the hMOF protein potentially serves as a new clinical marker of ovarian cancer prognosis.

Membranous expressions of Lewis y and CAM-DR-related markers are independent factors of chemotherapy resistance and poor prognosis in epithelial ovarian cancer.

BACKGROUND: Chemotherapy resistance is a common problem faced by patients diagnosed with epithelial ovarian cancer (EOC). Currently there are no specific or sensitive clinical biomarkers that maybe implemented to identify chemotherapy resistance and give insight to prognosis. The aim of this study is to investigate the roles of Lewis y antigen and the markers associated with cell-adhesion-mediated drug resistance (CAM-DR) in patients with EOC. METHODS: 92 EOC patients who were treated with systemic chemotherapy after cytoreductive surgery were included in this analysis. Patients were divided into two groups, chemotherapy sensitive (n = 56) and resistant (n = 36). Immunohistochemical (IHC) staining for Lewis y and CAM-DR-related cell surface proteins including CD44, CD147, HE4 (Human epididymis protein 4), integrin α5, ß1, αv and ß3 were conducted on tissues collected during primary debulking surgery. Using multivariate logistic regressions, IHC results were compared to clinical variables and chemotherapy resistance to determine possible correlations. The relationships between IHC expression and progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox regression analysis. RESULTS: Membranous expression of Lewis y and all these CAM-DR-related markers were significantly higher in the resistant group than that of the sensitive group (all P < 0.01). Multivariate regression analysis revealed that high expression of Lewis y, CD44, HE4, integrin α5 and ß1 as well as advanced FIGO stage were independent risk factors for chemotherapy resistance (all P < 0.05). Advanced FIGO stage, lymph node metastasis and high expression of Lewis y, CD44, CD147, HE4, integrin α5, ß1 were associated with a shorter PFS and OS (all P < 0.05). Moreover, multivariate COX analysis demonstrated that the following variates were independent predictors of worse PFS and OS survival: late FIGO stage (P = 0.013, 0.049), high expressions of Lewis y (P = 0.010, 0.036), HE4 (P = 0.006, 0.013) and integrin ß1 (PFS, P = 0.003), integrin α5 (OS, P = 0.019). CONCLUSION: Membranous expression of Lewis y and CAM-DR-related markers including CD44, CD147, HE4, integrin α5, ß1, αv and ß3 are associated with the development of chemotherapy resistance. High expression of Lewis y antigen and CAM-DR-related markers including CD44, CD147, HE4, integrin α5 and ß1 are independent markers for PFS and OS, in which Lewis y and HE4 are the most significant.

Expression of CD147 and Lewis y antigen in ovarian cancer and their relationship to drug resistance.

The purpose of this study was to investigate the relationship between the expression of CD147 and Lewis y antigen in epithelial ovarian carcinoma tissues and resistance to chemotherapeutic drugs, and its underlying clinical significance, and to analyze the correlation between the expression of CD147 and Lewis y antigen. Ninety-two ovarian cancer patients were divided into a chemotherapeutic-drug-resistant group (34 patients) and a drug-sensitive group (58 patients). Immunohistochemical assays were used to measure CD147, and Lewis y antigen to investigate their correlation with chemotherapy resistance. Multivariate logistic regression was used to analyze the relationships between risk factors and resistance to chemotherapy in ovarian cancer. Cox's model was used to analyze the relationships between risk factors and prognosis. The proportion of tissues expressing CD147 and Lewis y antigen in the drug-resistant group were 94.12 and 91.67%, respectively, which were significantly higher than those in the sensitive group (77.59 and 60.34%, respectively). The multivariate analysis indicated that the expression of CD147 and Lewis y antigen and the pathological stage of the ovarian cancer were all independent risk factors for drug resistance. Expression of CD147 and Lewis y antigen was high in the resistant group, and they correlated positively with each other. The expression of CD147 and Lewis y antigen was significantly higher in the drug-resistant group and their expression correlated positively in the ovarian epithelium. The expression of CD147 and Lewis y antigen and the pathological stage of ovarian cancer were all independent risk factors for drug resistance and prognosis in ovarian cancer.

Expression of Lewis y antigen and integrin αv, ß3 in ovarian cancer and their relationship with chemotherapeutic drug resistance.

OBJECTIVE: This study investigates the expression of Lewis y antigen, integrin αv, ß3 in epithelial ovarian cancer tissues. We further evaluate the relationship between their expression and chemotherapy resistance of ovarian cancer and its possible clinical significance. METHODS: Tissues of 92 patients with ovarian cancer meeting the inclusion criteria with complete follow-up data were enrolled and divided into chemotherapy resistant group and sensitive group. The expression and relationship of Lewis y antigen and integrin αv, ß3 are assessed in paraffin sections using immunohistochemistry and double-labeling immunofluorescence method. Multivariate logistic regression analysis was used to investigate the relationship between age, clinical stage, differentiation, histologic subtype, Lewis y antigen and integrin αv, ß3 expression in ovarian cancer patients. RESULTS: The expression rates of Lewis y antigen and integrin αv in the resistant group, significantly higher than the rates found in the sensitive group (p <0.05). Multivariate analysis showed that the expression of Lewis y antigen, integrin αv and ovarian cancer's clinical stage were independent, drug resistance-related risk factors. The expression levels of Lewis y antigen and integrin αv, ß3 were positively correlated with each other. CONCLUSIONS: A close correlation between Lewis y antigen, integrin αv, ß3 and ovarian cancer was observed. Lewis y antigen can influence the biological behavior of a tumor cell as an important composition of integrin αv, ß3 by some signal pathway. And the expression of Lewis y antigen, integrin αv and ovarian cancer's clinical stage are both independent, drug resistance-related risk factors.

High expression of Lewis y antigen and CD44 is correlated with resistance to chemotherapy in epithelial ovarian cancers.

OBJECTIVES: To measure Lewis y antigen and CD44 antigen expression in epithelial ovarian carcinoma and to correlate the levels of these antigens with clinical response to chemotherapy. METHODS: The study cases included 34 cases of ovarian carcinoma with resistance to chemotherapeutic drugs, 6 partially drug-sensitive cases, and 52 drug-sensitive cases (92 total). RESULTS: The rates of expression of Lewis y antigen and CD44 antigen were significantly greater in the drug-resistant group than that in the partially-sensitive or sensitive groups. Surgical stage, residual tumor size and expression of CD44 and Lewis y antigen in ovarian carcinoma tissues were independent risk factors for chemotherapeutic drug resistance. CONCLUSIONS: Over-expression of Lewis y and CD44 antigen are strong risk factors for chemotherapeutic drug resistance in ovarian carcinoma patients.

Three novel CYP17A1 gene mutations (A82D, R125X, and C442R) found in combined 17α-hydroxylase/17,20-lyase deficiency.

The aim of this study was to analyze the structure and functional consequences of 3 novel mutations (A82D, R125X, and C442R) of the CYP17A1 gene found in 2 patients with combined 17α-hydroxylase/17,20-lyase deficiency (17OHD). Two Chinese 46, XY female patients were diagnosed with 17OHD based on clinical findings and biochemical results. The CYP17A1 gene was analyzed by polymerase chain reaction direct sequencing. An in vitro expression system was performed in HEK293 cells to analyze the mutant P450c17 activity compared with the wild type. Analysis of the CYP17A1 gene sequences in patient 1 showed compound heterozygous mutations A82D (g.417 C > A) in exon 1 and Y329fs (g.4869 T > A, 4871del) in exon 6; DNA sequencing analysis in patient 2 revealed compound heterozygous mutations R125X (g.2045 C > T) in exon 2 and C442R (g.6457 T > C) in exon 8. The mutations A82D, R125X, and C442R have not been reported previously. The functional study demonstrated that the A82D, R125X, and C442R mutations almost completely eliminate enzymatic activity. These results, which indicate that Ala 82 and Cys 442 are crucial for both 17-hydroxylase and 17,20-lyase activities, help define the structure-function relationship of the CYP17A1 gene. The novel mutations A82D, R125X, and C442R further clarify the patients' clinical manifestations of combined 17OHD.