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Wnt-11 is a positive regulator of the Wnt signaling pathway, which plays a crucial role in carcinogenesis. However, Wnt-11 expression in cervical cancer has not been well investigated. The aim of this study was to investigate the role of Wnt-11 in cervical tumor proliferation and invasion. This study examined 24 normal cervical squamous epithelia, 29 cervical intraepithelial neoplasia (CIN), and 78 cervical cancer samples. The expression of Wnt-11 was investigated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction analysis. The expression of the high-risk human papilloma virus (HR-HPV) E6 oncoprotein was also investigated by immunohistochemistry. In addition, the expression of Wnt-11, HR-HPV E6, JNK-1, phosphorylated JNK-1(P-JNK1), and β-catenin was examined by western blot analysis following Wnt-11 knockdown or overexpression in HeLa or SiHa cells, respectively. The promotion of cervical cancer cell proliferation and invasion was investigated using the cell counting kit-8 and Matrigel invasion assay, respectively. Wnt-11 and HR-HPV E6 expression increased in a manner that corresponded with the progression of cervical cancer and was significantly correlated with the International Federation of Gynecology and Obstetrics cancer stage, lymph node metastasis, tumor size, and HPV infection. Wnt-11 protein expression was positively associated with HR-HPV E6 protein expression in all 78 cervical cancer samples (P < 0.001). Furthermore, Wnt-11 was positively associated with P-JNK1 expression and promoted cervical cancer cell proliferation and invasion. These observations suggest that the increased Wnt-11 expression observed in cervical cancer cells may lead to the phosphorylation and activation of JNK-1 and significantly promote tumor cell proliferation and cell migration/invasion through activation of the Wnt/JNK pathway. Consequently, Wnt-11 may serve as a novel target for cervical cancer therapy.

The purpose of the study was to determine the expression patterns of Wnt-11 and squamous cell carcinoma antigen in cervical cancer tissues and to explore their clinical significance and correlation with clinicopathological parameters. The expression of Wnt-11 and squamous cell carcinoma antigen was detected in 127 cervical cancer tissues, 21 cervical intraepithelial neoplasia, as well as in 20 healthy controls by immunohistochemistry, and the relationship of Wnt-11 and squamous cell carcinoma antigen expression with clinicopathological parameters was analyzed. Both Wnt-11 and squamous cell carcinoma antigen were more commonly expressed in cervical cancer than in cervical intraepithelial neoplasia and in normal cervical tissue (respectively; P < 0.05); further, Wnt-11 and squamous cell carcinoma antigen expression in cervical cancer were positively correlated (r = 0.271, P < 0.05). In comparing the expression with clinicopathological parameters of tumor samples, Wnt-11 and squamous cell carcinoma antigen were both associated with FIGO stage, lymph node metastasis, and tumor size (P < 0.05), but not with patient age, pathological type, or differentiation. Increased Wnt-11 protein levels in cervical carcinoma samples were associated with a poor outcome in univariate and multivariate analysis. Wnt-11 and squamous cell carcinoma antigen are related to the malignancy degree and metastasis of cervical cancer, and thus may play a coordinating role in the occurrence and progression of cervical cancer. The study indicated that Wnt-11 may be a useful prognostic indicator for cervical carcinoma.

Background: The p21 codon 31 single nucleotide polymorphism (SNP), rs1801270, has been linked to cervical cancer but with controversial results. The aims of this study were to investigate the role of p21 SNP-rs1801270 and other untested p21 SNPs in the risk of cervical cancer in a Chinese population., Methods: We genotyped five p21 SNPs (rs762623, rs2395655, rs1801270, rs3176352, and rs1059234) using peripheral blood DNA from 393 cervical cancer patients and 434 controls., Results: The frequency of the rs1801270 A allele in patients (0.421) was significantly lower than that in controls (0.494, p = 0.003). The frequency of the rs3176352 C allele in cases (0.319) was significantly lower than that in controls (0.417, p < 0.001).The allele frequency of other three p21 SNPs showed not statistically significantly different between patients and controls. The rs1801270 AA genotype was associated with a decreased risk for the development of cervical cancer (OR = 0.583, 95%CI: 0.399 - 0.853, P = 0.005). We observed that the three p21 SNPs (rs1801270, rs3176352, and rs1059234) was in linkage disequilibrium (LD) and thus haplotype analysis was performed. The AGT haplotype (which includes the rs1801270A allele) was the most frequent haplotype among all subjects, and both homozygosity and heterozygosity for the AGT haplotype provided a protective effect from development of cervical cancer., Conclusions: We show an association between the p21 SNP rs1801270A allele and a decreased risk for cervical cancer in a population of Chinese women. The AGT haplotype formed by three p21 SNPs in LD (rs1801270, rs3176352 and rs1059234) also provided a protective effect in development of cervical cancer in this population.

Background: Studies have shown that type-specific persistence of high-risk human papillomavirus (HPV) infection contributed significantly to cervical carcinogenesis., Methods: In this population-based study (on 24041 women), we report on the prevalent genotypes of HPVs and the prevalent genotypes of HPV persistent infection in the northeast of China., Results: Our results showed that in HPV infected women (45.6% in total), (95% CI, 44.97%-46.23%), 17.35% (95%CI, 16.87%-17.83%) suffered persistent infection. The most common high-risk HPV types in persistent positivity were HPV-16 (18.21%; 95%CI, 17.04%-19.38%), HPV-58 (13.2%; 95%CI, 12.17%-14.23%), HPV-18 (8.66%; 95%CI, 7.81%-9.51%), HPV-52 (7.06%; 95% CI, 6.28%-7.84%) and HPV-33 (6.78%; 95% CI, 6.02%-7.54%). The prevalence of persistent infections with HPV-16,-58, -18, -52 and 33 in cervicitis were lower compared to those in CIN (all P < 0.05). HPV-58, -33 and multiple HPV persistent positivity were significantly associated with older age (all P < 0.05). HPV-18 persistent positivity was significantly associated with adenocarcinoma and lymphatic metastasis (all P < 0.05). HPV-18 persistent positivity was associated with cervical cancer prognosis (P <0.0001). Multivariate analyses showed that HPV-18 persistent positivity, (RR = 1.704, 95%CI = 1.095-2.654, p = 0.028) and lymphatic metastasis (RR = 2.304, 95%CI = 1.354-3.254, P = 0.015) were independent predictors for 3-year survival in cervical cancer., Conclusions: we provided extensive results of HPV genotype prevalence and distribution in the northeast of China. HPV genotyping is worthwhile to perform because of its independent prognostic value in cervical cancer.

Cyclin D1, with a common G/A polymorphism in rs9344, is an essential regulator of the G1 phase in cell cycles and plays an important role in several tumor types, and the homology of cyclin D1 with human papillomavirus (HPV)-16 E7 brought our attention to CCND1 gene in cervical cancer. A total of 738 native Chinese subjects consist of 327 cases and 411 controls were enrolled in this study. CCND1 genotyping was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and partially verified by sequencing of genomic DNA and cDNA. The transcription of cyclin D1 mRNA isoforms was analyzed by quantitative PCR; expression of protein isoforms by immunohistochemistry and Western blotting. We observed that the AA genotype had decreased risk of developing cervical cancer (odds ratio [OR] = 0.332; 95% confidence interval [CI] = 0.113-0.978; P = 0.045). The two mRNA isoforms were both transcripted from A and G allele. Transcript b decreased in squamous cell carcinoma of the uterine cervix (SCCUC) group (P = 0.004), especially poorly differentiated group (P = 0.004), and in G allele group of normal subjects (P = 0.001). In immunohistochemistry analysis, cyclins D1, D1a, and D1b failed to correlate with cervical cancer (P = 0.808, 0.445, and 0.095). However, cyclin D1b was downregulated in SCCUC group analyzed by Western blotting (P = 0.039). This study indicates that CCND1 rs9344 polymorphisms confer host susceptibility to cervical cancer. A allele possesses a relative protective effect probably through the cyclin D1b's inhibition on HPV carcinogenesis., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: While HPV infection is the main cause of cervical cancer, genetic susceptibility to HPV infection is not well understood. Tumor necrosis factor alpha (TNF-alpha), involved in the defense against HPV infection, plays an important role in cervical cancer progression and regression. The aim of this study was to investigate the relationship between the TNF-alpha rs1800629 polymorphism and risk of HPV infection or cervical cancer., Methods: Three groups were involved in this study of Chinese women. Group 1 consisted of 285 high risk HPV positive cervical cancer patients, Group 2, 225 high risk HPV positive patients without cervical cancer, and Group 3, 318 HPV negative women with no cervical cancer. Blood samples were obtained from all patients and genotyped by PCR-RLFP. Fifty randomly selected samples were further sequenced., Results: The allele and genotype distributions of the TNF-alpha rs1800629 polymorphism were not significantly different between each of the groups (P>0.05). There are no significant relationship between rs1800629 polymorphism and high risk HPV infection (OR = 0.649, 95% CI: 0.253-1.670, P = 0.371), cervical cancer (OR = 0.993, 95% CI: 0.376-2.618, P = 0.988), or cervical cancer with HPV infection (OR = 0.663, 95% CI: 0.250-1.758, P = 0.409)., Conclusions: We demonstrated that there is no association between TNF rs1800629 polymorphism and the HPV infection, or cervical cancer with HPV infection.

Aim: The expression of Dkk-3, as a number of the Dkk family was different in different cancer. Because Dkk-3 encodes a secreted protein, we investigated whether the Dkk-3 protein is secreted into the sera of patients with gynecological cancer., Material & Methods: The levels of Dkk-3 protein were assessed by enzyme-linked immunosorbent assay in the sera of 104 patients with gynecological cancer: 36 with ovarian, 40 with cervical and 28 with endometrial cancers., Results: The serum levels of Dkk-3 protein in patients with ovarian cancer [25.54 (7.99) pg/mL] was lower than in normal individuals [42.08 (14.89) pg/mL] (P = 0.000). But serum levels of Dkk-3 protein in patients with cervical [166.39 (300.68) pg/mL] (P = 0.013) and endometrial cancers [73.64 (23.36) pg/mL] (P = 0.000) were higher than in normal individuals. The serum levels of Dkk-3 protein were associated with clinical stage in patients with cervical and endometrial cancers. In patients with ovarian cancer, the serum levels of Dkk-3 protein were associated with lymphatic metastasis. In patients with cervical cancer, the serum levels of Dkk-3 protein were associated with tumor diameters., Conclusion: Dkk-3 protein detection using enzyme-linked immunosorbent assay as molecular markers can contribute to detection and diagnosis of gynecological cancer, especially for ovarian cancer and endometrial cancer.