Clinical analysis of 175 cases of vaginal intraepithelial neoplasia.

OBJECTIVE: To evaluate the risk factors related to vaginal intraepithelial neoplasia (VaIN) severity. STUDY DESIGN: This retrospective study included patients with histologically confirmed VaIN diagnosed at Hubei Provincial Maternal and Child Health Hospital, China, between January 2017 and October 2021. The primary outcomes were persistence, remission, progression, and recurrence. Multiple ordinal logistic regression analysis was used to analyze the risk factors of VaIN severity. RESULTS: A total of 175 patients were included, 135 (77.1%) with VaIN 1, 19 (10.9%) with VaIN 2, and 21 (12%) with VaIN 3. Patients with VaIN 3 were older than those with VaIN1 2 (P < 0.001). The ratio of patients with concomitant cervical lesions increased with VaIN grade (23.7%, 47.4%, and 47.6% for VaIN 1, 2, and 3, respectively). The proportion of patients with intraepithelial neoplasia (CIN) 3 increased with the VaIN grade (3.1%, 44.5%, and 80% for VaIN 1, 2, and 3, respectively, respectively; all P < 0.001). In patients with VaIN 1, 19.4% had regression (spontaneous regression in 90.5%) and 80.6% underwent laser ablation (regression in 93.1%). In patients with VaIN 2 and 3, 3.1% showed no regression, 53.1% underwent laser ablation (regression in 76.4%), and 73.8% underwent excision (regression in 78.7%). Age (OR = 1.05, 95 %CI: 1.01-1.10, P = 0.010) and concomitant cervical lesion (OR = 6.99, 95 %CI: 2.31-21.12, P = 0.001) were independent risk factors for the severity of VaIN. CONCLUSION: Age and cervical lesions might be the risk factors for VaIN severity.

Foxo3a-Mediated DNMT3B Impedes Cervical Cancer Cell Proliferation and Migration Capacities through Suppressing PTEN Promoter Methylation.

OBJECTIVE: Cervical cancer is linked with the constitutive activation of growth factors and gene mutations-induced pro-survival signaling pathways. Herein, we purposed to explore the possible molecular mechanism of Foxo3a-mediated DNMT3B in the proliferation and migration of cervical cancer cells via mediating the PTEN promoter methylation. METHODS: Foxo3a expression in cervical cancer was tested by qRT-PCR and western blot experiments. The cervical cancer cell biological functions with overexpression of Foxo3a were evaluated by CCK-8 assay, Transwell experiment, and flow cytometry, respectively. MS-PCR was utilized for testing the PTEN methylation levels, and ChIP experiment was implemented for evaluating the enrichment of DNMT3B in the PTEN promoter region and the binding of Foxo3a and DNMT3B. The PTEN methylation and interference with Foxo3a expression were performed in cervical cancer cells, and then their impacts on cervical cancer cell biological functions were observed. RESULTS: FOXO3a was expressed at a low level in cervical cancer, and its overexpression contributed to a reduction in cell proliferative, migratory and invasive capabilities, and an elevation in apoptosis rate. Foxo3a blocked its methylation with the PTEN promoter by repressing DNMT3B activity. Upon treatment with methyltransferase inhibitor (5-aza-dc), the malignant phenotypes of cervical cancer cells were diminished. 5-aza-dc neutralized the impacts of silencing Foxo3a on malignant phenotypes. CONCLUSION: This research underlines that Foxo3a blocks its methylation with the PTEN promoter by inhibiting DNMT3B activity, which subsequently impedes cervical cancer cell progression.

OTX1 promotes tumorigenesis and progression of cervical cancer by regulating the Wnt signaling pathway.

Cervical cancer is a common malignant tumor in females. Orthodenticle homolog 1 (OTX1) serves a key role in the occurrence and progression of tumors. The present study aimed to investigate the role and potential mechanism of OTX1 in cervical cancer. OTX1 expression was analyzed by western blotting, reverse transcription­quantitative PCR and immunohistochemistry. MTT assay was performed to assess cell viability. EdU and colony formation assay were used to measure cell proliferation. Wound healing and Transwell assays were performed to measure cell migration and invasion. Western blot assay was performed for the assessment of protein expression. Gene set enrichment analysis (GSEA) was performed to analyze signaling pathways regulated by OTX1. Co­Immunoprecipitation assay was performed to confirm the interaction between OTX1 and Wnt9b. In cervical cancer tissue and cells, OTX1 was significantly upregulated. OTX1 overexpression promoted proliferation, migration and invasion of cervical cancer cells. OTX1 silencing significantly decreased cell proliferation, migration and invasion of cervical cancer. GSEA showed that OTX1 activated the Wnt signaling pathway. OTX1 silencing inhibited the increased levels of adenomatous polyposis coli (APC), glycogen synthase kinase (GSK)­3ß and axis inhibition protein (AXIN)2 and decreased levels of Wnt9b and ß­catenin. OTX1 overexpression decreased the levels of APC, GSK­3ß and AXIN2 and increased levels of Wnt9b and ß­catenin. However, XAV939 (a Wnt signaling inhibitor) and ß­catenin silencing partly eliminated the effect of OTX1 overexpression on cervical cancer cells. OTX1 promoted the progression of cervical cancer by activating the Wnt signaling pathway.

dbCerEx: a web-based database for the analysis of cervical cancer transcriptomes.

BACKGROUND: Cervical cancers are ranked the second-most hazardous ailments among women worldwide. In the past two decades, microarray technologies have been applied to study genes involved in malignancy progress. However, in most of the published microarray studies, only a few genes were reported leaving rather a large amount of data unused. Also, RNA-Seq data has become more standard for transcriptome analysis and is widely applied in cancer studies. There is a growing demand for a tool to help the experimental researchers who are keen to explore cervical cancer gene therapy, but lack computer expertise to access and analyze the high throughput gene expression data. DESCRIPTION: The dbCerEx database is designed to retrieve and process gene expression data from cervical cancer samples. It includes the genome wide expression profiles of cervical cancer samples, as well as a web utility to cluster genes with similar expression patterns. This feature will help researchers conduct further research to uncover novel gene functions. CONCLUSION: The dbCerEx database is freely available for non-commercial use at http://128.135.207.10/dbCerEx/, and will be updated and integrated with more features as needed.

[Significance of DNA ploidy analysis in diagnosis of ASCUS].

OBJECTIVE: To investigate the significance of DNA ploidy analysis in diagnosis of atypical squamous cell of undetermined significance (ASCUS). METHODS: From Jan.2009 to Jul.2011, 875 women with ASCUS confirmed by liquid based thin layer cytology technique underwent DNA ploid analysis in Hubei Maternal and Child Health Hospital. Among 294 women underwent high risk HPV detection. All subjective were examined colposcopy directed biopsy at day 3 to 10 after menstruation. RESULTS: Among 875 ASCUS cases, 553 cases with histologically as chronic cervicitis (63.2%), 165 cases with cervical intraepithelial neoplasia (CIN)I (18.9%), 45 cases with CINII (5.1%), 79 cases with CINIII (9.0%) and 33 cases with cervical invasive cancer (3.8%) were confirmed by colposcopy. Totally 532 cases were observed with DNA heteroploid, and 343 were not observed with DNA heteroploid. When DNA heteroploid negative and more than or equal to three ploid were used to predict CINII or more severe cervical diseases, the sensitivity, specificity, positive predictive values and negative predictive values were 98.7% and 90.3%, 47.5% and 46.1%, 29.1% and 40.8%, 99.4% and 92.1%, respectively. The amount of heteroploid cells > 2.5c and > 5c among every 100 detected cells in chronic cervicitis and CINI, CINII, CINIII and cervix cancer were respectively 2.53 ± 1.99 and 0.10 ± 0.07, 2.24 ± 1.69 and 0.20 ± 0.11, 4.10 ± 1.91 and 0.28 ± 0.19, 7.97 ± 7.33 and 1.27 ± 1.23, 8.99 ± 7.33 and 0.36 ± 0.33, there was no statistical difference in amount of heteropolid cells between >2.5c and > 5c at group of chronic cervicitis and CINI, CINIII and cervix cancer (P > 0.05). However, the amount of heteroploid cells at > 2.5c and > 5c at group of chronic cervicitis, CINI, CINIII and cervical were higher than that of CINII significantly (P < 0.05). Among 294 cases with high risk (HR) HPV detection, 216 cases were HR-HPV positive, and 78 cases were HR-HPV negative. The pathology result by colposcopy at group of negative heteroploid, heteroploid < 3, or ≥ 3 showed statistical distribution (χ(2) = 115.2775, P < 0.01). CONCLUSION: DNA ploidy analysis can be used for ASCUS diagnosis, which can avoid excessive biopsy under colposcopy, in the mean time, CIN and cervical cancer could decrease missed diagnosis.