Yuting Hu

Expression of Sox2 in human ovarian epithelial carcinoma

ObjectivesThe aim of this study was to investigate the expression of Sox2, a transcription factor, in a series of benign, borderline, and malignant ovarian tumors and to evaluate whether Sox2 expression levels correlate with clinicopathological characteristics in ovarian epithelial carcinoma.MethodsThis study investigated immunohistochemical expressions of Sox2 in 43 species of normal ovarian epithelia, 284 species of serous epithelial lesions, and 164 species of mucinous epithelial lesions to assess their clinicopathological relevance.ResultsImmunohistochemical results showed that the positive ratio of Sox2 expression gradually increased from benign and borderline to malignant ovarian tumors; 55.81% of normal ovarian epithelia, ~65% of serous and mucinous cystadenoma, ~70% of borderline serous and mucinous cystadenoma, and ~91% of serous and mucinous cystadenocarcinoma expressed Sox2, respectively. However, there was no significant correlation between Sox2 expression and the age and level of CA125 in patients with either serous or mucinous tumors. Positive correlations between Sox2 expression levels and FIGO stage or pathological stage were identified in both serous and mucinous cystadenocarcinoma samples.ConclusionThe expression level of Sox2 in human ovarian tumors was directly proportional to their degree of malignancy, implying that Sox2 overexpression may be closely related to the malignant transformation of ovarian tumors.

Nanog Is Highly Expressed in Ovarian Serous Cystadenocarcinoma and Correlated with Clinical Stage and Pathological Grade

Objective: Nanog is overexpressed in embryonic stem cells for cell self-renewal and differentiation. We investigated whether the Nanog expression is associated with the occurrence and development of ovarian cancer. Methods: Immunohistochemistry was used to examine the expression of Nanog in 43 normal ovarian epithelia, 110 serous cystadenomas, 80 borderline serous cystadenomas, and 107 serous cystadenocarcinomas. In the meantime, their association with various clinicopathologic features was assessed. Results: The expression intensity of Nanog in normal ovarian tissue, benign, borderline, and malignant tumors showed a gradual rising trend. Among the serous cystadenocarcinomas, 42.86% were detected to be positive for stage I, 70.97% for stage II, 95.31% for stage III, and 100% for stage IV. There was a strong correlation between Nanog and clinical stage (r = 0.418, p = 0.000). Besides, there was a 55.56% positive expression of grade I, 73.68% of grade II, and 96.67% of grade III. The correlation between Nanog and differentiation grade was dramatic (r = 0.692, p = 0.000). Conclusions: Nanog was highly expressed in ovarian serous cystadenocarcinoma, and showed a positive correlation with clinical stage and grade. Nanog may play an important role in the development of dedifferentiation and progression of serous ovarian carcinoma.

Gene silencing of HPV16 E6/E7 induced by promoter-targeting siRNA in SiHa cells.

Background:Recently, transcriptional gene silencing induced by small interfering RNA (siRNA) was found in mammalian and human cells. However, previous studies focused on endogenous genes.Methods:In this study, we designed siRNA targeting the promoter of human papillomavirus 16 E6/E7 and transfected it into the cervical cancer cell line, SiHa. E6 and E7 mRNA and protein expression were detected in cells treated by promoter-targeting siRNA. Futhermore, cellular growth, proliferation, apoptosis and senescence were detected. Thereafter, we investigated promoter DNA methylation and histone methylation status in cells treated with promoter-targeting siRNA.Results:We found that E6/E7 mRNA and protein were simultaneously reduced, cell growth and proliferation were inhibited and cell death, especially senescence, was remarkably increased. Meanwhile, we also found a significantly increasing histone H3-Lys9 methylation on the promoter when E6/E7 gene expression was inhibited.Interpretation:Our findings suggest that promoter-targeting siRNA effectively and simultaneously knocks down both extraneous HPV 16 E6 and E7 at the transcriptional level, and consequently inhibits proliferation and induces death in HPV 16-infected cells. This transcriptional repression is probably induced by histone modification rather than by alteration of DNA methylation.

Stage-specific embryonic antigen 4 expression in epithelial ovarian carcinoma.

Introduction: Stage-specific embryonic antigen 4 (SSEA-4) is a widely used marker to monitor the differentiation of pluripotent embryonic stem cells. Little is known about the expression pattern of SSEA-4 in solid tumors up to now. Methods: In this study, we investigated the expression of SSEA-4 in 479 cases of various degrees of ovarian epithelial lesions by immunohistochemistry, consisting of 45 normal ovarian epithelia, 110 benign serous ovarian cystadenomas, 68 borderline serous ovarian cystadenomas, 104 invasive serous ovarian carcinomas, 64 benign serous mucinous cystadenomas, 48 borderline mucinous ovarian cystadenomas, and 40 invasive mucinous carcinomas. Moreover, the association between SSEA-4 expression and clinicopathological parameters was also evaluated. Results: The expression of SSEA-4 was found to be increased from normal epithelium to benign cystadenoma and to borderline cystadenoma and adenocarcinoma in both serous and mucinous group. The loss or reduction of the expression of SSEA-4 was significantly correlated with more advanced tumor stage and poorer tumor cell differentiation. Conclusions: We therefore proposed that SSEA-4 may play a role during the oncogenesis of epithelial ovarian carcinoma and posses a tumor suppressor effect during malignancy promotion. It could be a potential therapy target in patients with epithelial ovarian carcinoma.

PARP-1 Val762Ala Polymorphism Is Associated with Risk of Cervical Carcinoma

PARP-1 is a nuclear enzyme that plays an important role in DNA repair, recombination, proliferation and the genome stability. The PARP-1 Val762Ala polymorphism has been associated with increased risk of developing cancers of the prostate, esophagus and lung. The aim of this study was to determine whether the PARP-1 Val762Ala polymorphism is associated with the risk of cervical carcinoma. MA-PCR was used to genotype the PARP-1 Val762Ala polymorphism in 539 women with cervical carcinoma, 480 women with CIN and 800 controls. The genotyping method was confirmed by the DNA sequencing analysis. The PARP-1 Val762Ala polymorphism was not associated with the risk of CIN. However, women carrying the PARP-1 Ala762Ala genotype were significantly susceptible to cervical carcinoma (OR: 2.70, 95% CI: 1.47–3.70), and the similar results were also found in squamous cell carcinoma (OR: 2.56, 95% CI: 1.47–3.70). In HPV positive population, the PARP-1 Ala762Ala genotype was also associated with increased risk of cervical carcinoma (OR: 5.56, 95% CI: 2.08–14.3). Our results indicate that the PARP-1 Ala762Ala genotype increases the risk of cervical carcinoma.

Expression of octamer-4 in serous and mucinous ovarian carcinoma

Background Octamer-4 (Oct4) is a well known regulator of self-renewal in embryonic stem cells; it has been detected in several human cancers and may play a critical role in carcinogenesis. Aims To assess the expression of Oct4 in epithelial ovarian tumours. Methods Expression of Oct4 was evaluated by immunohistochemistry in 460 cases of various epithelial ovarian lesions as well as 35 cases of normal fallopian tube epithelium. The association between Oct4 expression and various clinical pathological parameters was analysed. Results Oct4 expression was significantly increased from normal epithelium (both ovarian epithelium and fallopian tube epithelium) to benign and borderline cystadenoma to carcinoma in the serous lesion subgroup. Oct4 overexpression was associated with more advanced FIGO stage and higher histological grade in serous adenocarcinoma. Conversely, Oct4 expression did not differ among mucinous lesions or correlate with clinicopathological parameters in patients with mucinous adenocarcinoma. Conclusion Results suggest that Oct4 expression may contribute to the initiation, promotion and progression of serous ovarian carcinoma; it might be a useful biomarker for the diagnosis and outcome prediction of serous ovarian carcinoma.

Expression of leukaemia inhibitory factor in epithelial ovarian carcinoma: correlation with clinical characteristics.

Sir: Leukaemia inhibitory factor (LIF) is a polyfunctional glycoprotein of the interleukin-6 family of cytokines, which has been shown to induce macrophage maturation and terminate self-renewal of the undifferentiated and highly clonogenic murine myeloid leukaemia M1, resulting in suppression of the leukaemia population. Subsequent studies have revealed that LIF is essential for maintenance of the totipotentiality of normal embryonic stem (ES) cells via inhibition of differentiation and maintenance of proliferation. Abnormal expression of key molecules has the potential to alter the balance between cell proliferation and differentiation, resulting in tumorigenesis. Hence, the ability of LIF to regulate both cell proliferation and differentiation suggests that it might be involved in the carcinogenesis of some tumours, though contradictory results have been reported. Previous studies have detected stem cells in tumour tissues, including ovarian cancer. Since LIF sustains the totipotentiality of ES cells, it is possible that LIF could be involved in the transformation of ovarian epithelial cells and the occurrence and development of epithelial ovarian carcinoma. LIF expression was examined by immunohistochemistry in 401 cases of ovarian epithelial lesions, including 49 normal ovarian epithelia, 91 serous cystadenomas,

The LIG4 Ile658Val polymorphism does not affect the risk of cervical carcinoma

The aim of this study was to investigate whether gene LIG4 genetic polymorphism affects the risk of cervical carcinoma. We studied 500 cervical carcinoma patients and 800 normal women as controls. Demographic and epidemiologic risk factors were recorded. Single nucleotide polymorphisms (SNPs) (LIG4 Ile658Val) were genotyped. Compared to LIG4 Ile658Ile (AA) genotype, LIG4 Ile658Val (AG) did not increase or decrease the risk of cervical carcinoma or cervical squamous cell carcinoma [ORs and 95% CIs being 1.07 (0.70-1.63) and 1.01 (0.65-1.55)], while no homozygous LIG4 Val658Val (GG) was found in the cervical carcinoma group. Analyzing the risk of variant LIG4 Ile658Val genotypes for cervical carcinoma of different histologic types or HPV infection status, we found striking similarities between the squamous cell carcinoma group and the HPV-positive group and the overall carcinoma. In conclusion, in the Chinese population, LIG4 Ile658Val has only a slight impact on the risk of developing cervical carcinoma.

Podocalyxin-like protein 1 expression and correlation with clinical characteristics in epithelial serous and mucinous ovarian carcinoma and tumor-like lesions.

Objective: Podocalyxin-like protein 1 (PCLP1) may be involved in the invasion and metastasis of tumors. However, to date the role of PCLP1 in the progression of epithelial ovarian carcinoma has not been investigated. Methods: PCLP1 expression was examined by immunohistochemistry in 471 cases with various degrees of ovarian epithelial lesions, including 46 cases of normal ovarian epithelial tissue, 105 benign serous tumors, 74 borderline serous tumors, 94 serous carcinomas, 58 benign mucinous tumors, 50 borderline mucinous tumors and 44 mucinous carcinomas. Associations between PCLP1 expression and various clinical characteristics were analyzed. Results: PCLP1 expression in mucinous carcinoma and borderline mucinous tumor tissues was found to be significantly lower than that observed in normal and benign mucinous tumor tissue. In addition, PCLP1 expression was significantly lower in mucinous carcinoma patients in advanced clinical stage and with poor differentiation of tumor cells. No positive results were observed in serous carcinomas. Conclusions: Our findings suggest that PCLP1 may be involved in the progression of ovarian mucinous lesions but not in serous lesions. Low PCLP1 expression may be a potential predictor of a poor prognosis in mucinous carcinomas.