PCNA in Cervical Intraepithelial Neoplasia and Cervical Cancer: An Interaction Network Analysis of Differentially Expressed Genes

The investigation of differentially expressed genes (DEGs) and their interactome could provide valuable insights for the development of markers to optimize cervical intraepithelial neoplasia (CIN) screening and treatment. This study investigated patients with cervical disease to identify gene markers whose dysregulated expression and protein interaction interface were linked with CIN and cervical cancer (CC). Literature search of microarray datasets containing cervical epithelial samples was conducted in Gene Expression Omnibus and Pubmed/Medline from inception until March 2021. Retrieved DEGs were used to construct two protein-protein interaction (PPI) networks. Module DEGs that overlapped between CIN and CC samples, were ranked based on 11 topological algorithms. The highest-ranked hub gene was retrieved and its correlation with prognosis, tissue expression and tumor purity in patients with CC, was evaluated. Screening of the literature yielded 9 microarray datasets (GSE7803, GSE27678, GSE63514, GSE6791, GSE9750, GSE29570, GSE39001, GSE63678, GSE67522). Two PPI networks from CIN and CC samples were constructed and consisted of 1704 and 3748 DEGs along 21393 and 79828 interactions, respectively. Two gene clusters were retrieved in the CIN network and three in the CC network. Multi-algorithmic topological analysis revealed PCNA as the highest ranked hub gene between the two networks, both in terms of expression and interactions. Further analysis revealed that while PCNA was overexpressed in CC tissues, it was correlated with favorable prognosis (log-rank P=0.022, HR=0.58) and tumor purity (P=9.86 × 10-4, partial rho=0.197) in CC patients. This study identified that cervical PCNA exhibited multi-algorithmic topological significance among DEGs from CIN and CC samples. Overall, PCNA may serve as a potential gene marker of CIN progression. Experimental validation is necessary to examine its value in patients with cervical disease.

Plicae Palmatae on MR in Uterus Didelphys: the Incidence and Morphological Characteristics

Objective: To investigate the incidence of plicae palmatae in uterus didelphys and its morphological characteristics on MR imaging. Methods: We retrospectively collected 37 consecutive female pelvic MR images diagnosed with uterus didelphys between August 2012 and November 2020. Patients with the following conditions were excluded: (a) repeated examination; (b) poor image quality; (c) cervical disease. Axial and coronal T2-weight images and axial three-dimensional (3D) volumetric isotropic T2-weighted acquisition (VISTA) were used to evaluate the ridge of plicae palmatae (RPP). A multiplanar reformation of the cervical axis from 3D-VISTA sequence was performed to measure the height and width of RPP. Non-normal variables based on the Kruskal-Wallis H test was used for statistical analysis. A two-tailed test where P < 0.05 was considered statistically significant. Results: Twenty-six cases were finally included in the statistics. The average age was 25.7±9.0 years (range, 10-45 years). RPP was observed on both cervices in 16 patients (61.5%), only on the left cervix in 3 patients (11.5%), and only on the right cervix in 4 patients (15.4%). There were 3 cases with no RPP observed in any of their cervix (11.5%).All RPP appear symmetrically on the anterior and posterior walls of the cervix. There was no statistically significant difference in height, width, and height/width of the RPP in the left and right cervix (p＞0.05). Conclusions: RPP is encountered in 88.5% patients with duplicated uterine cervices in our cohort. This incidence is similar to that reported in women with normal uterus of reproductive age.

Metabolic reprogramming in cervical cancer and metabolomics perspectives

Cumulative studies have shown that metabolic reprogramming is a hallmark of malignant tumors. The emergence of technological advances, such as omics studies, has strongly contributed to the knowledge of cancer metabolism. Cervical cancer is among the most common cancers in women worldwide. Because cervical cancer is a virus-associated cancer and can exist in a precancerous state for years, investigations targeting the metabolic phenotypes of cervical cancer will enhance our understanding of the interference of viruses on host cells and the progression of cervical carcinogenesis. The purpose of this review was to illustrate metabolic perturbations in cervical cancer, the role that human papillomavirus (HPV) plays in remodeling cervical cell metabolism and recent approaches toward application of metabolomics in cervical disease research. Cervical cancer displays typical cancer metabolic profiles, including glycolytic switching, high lactate levels, lipid accumulation and abnormal kynurenine/tryptophan levels. HPV, at least in part, contributes to these alterations. Furthermore, emerging metabolomics data provide global information on the metabolic traits of cervical diseases and may aid in the discovery of biomarkers for diagnosis and therapy.

Human Papillomavirus E6E7 mRNA and TERC lncRNA in Situ Detection in Cervical Scraped Cells and Cervical Disease Progression Assessment

BackgroundHuman papillomavirus screen in female cervical cells has demonstrated values in clinical diagnosis of precancerous lesions and cervical cancers. Human papillomavirus tests of cervical cells by utilizing Polymerase Chain Reaction (PCR) method provides human papillomavirus infection status however no further virus in situ information. Although it is well known that the tests of human papillomavirus E6/E7 RNA location in infected cervical cells and cell internal malignancy molecular will provide clues for gynecologists to evaluate disease progression, there are technique difficulties to preserve RNAs in cervical scraped cells for in situ hybridization. MethodsIn current study, after developing a cervical cell collection and preparation methods for RNA in situ hybridization, we captured the chance to screen 98 patient cervical cell samples and detected human papillomavirus E6/E7 mRNAs of high-risk subtypes, low-risk subtypes and lncRNA TERC in the cells. ResultsThere are 70% consistence between human papillomavirus PCR and human papillomavirus RNA in situ hybridization results in cervical collected cells. Viral E6/E7 mRNAs were observed to distribute in cervical cell nuclear and cytoplasm. Moreover, viral gathered clusters were observed outside of cells through human papillomavirus RNA in situ hybridization. Varied numbers of human papillomavirus infective cells were detected by RNAscope assay in different patients even though they are all human papillomavirus high-risk subtype positive discovered by human papillomavirus PCR results. A cell malignancy related long non-coding RNA, TERC, has been detected in seven patient samples. The patient follow-up information was further analyzed with RNAscope results which indicated a combination of RNAscope positive signals of TERC and human papillomavirus high risk signals in more than 10 cells (cytoplasm or nucleus) may connect with cervical lesion fast progression which deserves further studies in the future.ConclusionsTaken together, current study has provided an observable clue for gynecologists to evaluate human papillomavirus infection stage and cell malignancy status which may contribute for assessment of cervical disease progression.

The structure of cervical diseases in women suffering from pelvic floor dysfunction

Background. The prevalence of pelvic floor dysfunction (PFD) is soaring steadily. The protrusion of the cervix beyond vaginal opening when exposed to environmental factors can lead to the development of dystrophic, sclerotic and neoplastic processes of the cervix, which are mediated by changes in the pH, biocenosis of the vagina and environmental factors. Aim. To study the pathogenesis of cervical diseases in patients with PFD. Materials and methods. The study design is an open-label prospective observational study. The study included 40 patients of reproductive age: 26 patients with cervical disease with PFD (PFD group), 14 patients without cervical disease and PFD made up the second group. Results. The patients included in the study were comparable in terms of age and body mass index. Pap smear analysis revealed that the average number of leukocytes is significantly higher in patients with PFD compared to patients in the group without PFD 5.5 (1.520.0) and 1.5 (1.56.5) respectively (p=0.040). In PFD group, a high prevalence of the following conditions was observed: cervical leukoplakia (15%), CIN1 (38.5%), CIN2 (8%), chronic cervicitis (38.5%). Onco-cytological test results reviewed where the high prevalence of parakeratosis and hyperkeratosis (15%), ASCUS (15%), LSIL (23%) and HSIL (8%) were also noteworthy. It was observed that human papillomavirus type 16 was predominant in PFD patient group. Conclusion. The data obtained indicates an increased risk of developing cervical diseases in patients with PFD.

In-vitro Anti-Cancer and Anti-Inflammatory Screening of Dodonaea viscosa

Background: The current investigation was done to assess the in vitro anticancer property of Dodonaea viscosa (D. viscosa) in three malignant growth cell lines and mitigating impact in RAW 264.7 macrophages. Methods: The hydroalcoholic remove D. viscosa was ready and tried against HCT-116 colon malignancy, MCF-7 bosom disease HeLa cervical disease cell lines. The cytotoxicity of concentrate was affirmed by MTT cheeky. The calming movement of concentrate was assessed utilizing LPS invigorated RAW 264.7 macrophages and the degree of incendiary middle people was estimated. Results: The anticancer impact of D. viscosa onHCT-116, MCF-7 and HeLa cell line with the IC50 worth of 60.43 ± 0.76 μg/ml,75.26 ± 0.45 μg/ml and 72.12 ± 0.87μg/ml individually. Further, in LPS stimulatedRAW264.7 macrophage cells, treatment with D. viscosa extract altogether decreased the raised level of NO, TNF-α and PGE2. Conclusion: This examination gave the proof to D. viscosa an anticancer and mitigating specialist. Further bioactive confinement and atomic examinations are needed to prove the impact of plant remove.

HPV Catch-up Vaccination is Effective but Cervical Screening Should Continue

This short communication reports additional research that extends the previously published article - Commentary: HPV Catch-Up Vaccination Reduces the Prevalence of HPV 16 and 18 Infections and Cervical Disease: A Retrospective Study.1 One limitation of that study was uncertainty as to whether the catch-up cohort had actually received HPV (human papillomavirus) vaccination. That information has now been obtained. 87 (59%) of the 147 patients in the catch-up cohort had received at least one dose of HPV bivalent vaccine. 69 of these (representing 79% of those vaccinated) had received three doses (as recommended at the time). Both the vaccinated and unvaccinated subsets of the catch-up cohort show a significant reduction in the prevalence of HPV 16 and/or 18 (with/without other high-risk types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) and of high grade cervical disease compared to an earlier unvaccinated cohort. These results confirm the efficacy of HPV catch-up vaccination and the existence of herd immunity following the introduction of national HPV vaccination campaigns. However, 34 patients (23%) in the catch-up cohort had high grade disease (cervical intraepithelial neoplasia [CIN] 2 or worse), 16 of whom had been vaccinated (12 with three doses, one with two doses and three with one dose of HPV bivalent vaccine) and four of those vaccinated had HPV 16 and/or 18 (with/without other high-risk types), the rest had other HPV high risk types. This emphasises the importance of maintaining cervical screening alongside HPV vaccination.