scholarly journals Identification and validation of the high expression of pseudogene TCAM1P in cervical cancer via integrated bioinformatics analysis

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuanhang Zhu ◽  
Chenchen Ren ◽  
Li Yang ◽  
Zhenan Zhang ◽  
Meiyuan Gong ◽  
...  

Abstract Background HPV as the main cause of cervical cancer has long been revealed, but the detailed mechanism has not yet been elucidated. The role of testis/cancer antigen in cervical cancer has been revealed. However, there are no reports about the statement of testis/cancer-specific non-coding RNA. In this study, we first proposed TCAM1P as a testis/cancer-specific pseudogene, and used a series of experimental data to verify its relationship with HPV, and analyzed its diagnosis value of high-grade cervical lesions and the mechanism of their high expression in cervical cancer. This provides a new direction for the prevention and treatment of cervical cancer. Methods The specific expression of pseudogenes in each tissue was calculated by “TAU” formula. ROC curve was used to judge the diagnosed value of TCAM1P for high-grade lesions. The proliferation ability of cells was measured by CCK8. The expression of TCAM1P, HPV E6/E7 were detected by qRT-PCR. The binding for RBPs on TCAM1P was predicted by starbase v2.0 database, then RIP assay was used to verify. Besides, Gene Ontology (GO) and KEGG enrichment analysis were performed with “clusterprofiler” R package. Results TCAM1P was specifically high-expressed in normal testicular tissue and cervical cancer. Interesting, with the severity of cervical lesions increased, the expression of TCAM1P increased, and TCAM1P could effectively diagnose high-grade cervical lesions. Besides, the expression of TCAM1P was HPV dependent, with highest expression in HPV-positive cervical cancer tissues. Furthermore, RIP assay showed that EIF4A3 regulated the expression of TCAM1P through binding with it. CCK8 assay showed that TCAM1P promoted the proliferation and the Gene ontology (GO) and KEGG Pathway enrichment analysis same suggested that TCAM1P is involved in multiple ways in cell proliferation including Cell cycle, DNA replication and etc. Conclusions In this study, we firstly proposed that TCAM1P is cancer/testis pseudogene and is regulated by HPV E6/E7 and EIF4A3. TCAM1P promotes the proliferation of cervical cancer cells and acts as promoter in cervical cancer. Otherwise, TCAM1P promote proliferation through regulating cell cycle and DNA replication, but more evidence needs to be provided to reveal the mechanism by which TCAM1P plays a role in cervical cancer.

2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
Ana Rita Fernandes Miranda da Costa ◽  
Cláudia Sousa ◽  
Erica Isidoro ◽  
Regina Silva ◽  
Cristiana Mourato

Abstract Background Persistent infection by high-risk Human Papillomavirus (hrHPV) are the major cause of cervical cancer. Studies report disparities in the incidence of infection and the various genotypes of this virus in different age groups, suggesting a higher frequency of hrHPV in young women and low-risk subtypes being predominant in older women. This study aimed to investigate the incidence and distribution of hrHPV genotypes in postmenopausal women as well as the correlation with the cytological findings. Methods 16 859 women, aged 50–64 years, performed cervical cancer screening test in Friuri Venezia Giulia region, Italy. The infection was evaluated by the Polymerase Chain Reaction methodology and the positive samples were evaluated by Liquid Based Cytology according to the Bethesda System from 2014. A statistical analysis was performed to study the molecular and cytological data of this population. Results hrHPV infection were found in 5.8% of the women and 78.3% of these were caused by hrHPV other than HPV16 and HPV18 (). Also, 65.7% of the positive samples were negative for intraepithelial lesion or malignancy while low grade squamous intraepithelial lesion was the most frequent (22.4%). There was an increase in the number of high-grade intraepithelial lesions in the presence of HPV16 compared to that recorded when this genotype was absent (20.8% vs. 8.5%). No cervical cancers were detected. Conclusions Infection with hrHPV is uncommon in postmenopausal women and it is mostly caused by subtypes less associated with the development of cervical cancer. Yet, HPV16 infection triggers the development of high-grade lesions.


2019 ◽  
Vol 69 (9) ◽  
pp. 1555-1565 ◽  
Author(s):  
Pierre Debeaudrap ◽  
Joelle Sobngwi ◽  
Pierre-Marie Tebeu ◽  
Gary M Clifford

Abstract Background Screening and treating premalignant cervical lesions (cervical intraepithelial neoplasia 2+ [CIN2+]) is an effective way to prevent cervical cancer, and recommendations exist for the monitoring of treatment success. Yet, there is no specific recommendation for human immunodeficiency virus (HIV)-infected women, who are at a known, increased risk of cervical cancer. Methods A systematic review was performed by searching MEDLINE, EMBASE, and Web of Science for studies published from January 1980 through May 2018. Eligible studies described the prevalence of histologically- and/or cytologically-defined lesions in HIV-infected women at least 6 months post-treatment. The primary endpoint was treatment failure, defined as the presence of residual and/or recurrent high-grade CIN2+/high-grade squamous intraepithelial lesions post-treatment. The pooled prevalence in HIV-infected women and the odds ratios (ORs) for HIV-infected compared to HIV-uninfected women were estimated using random-effects models. Results Among 40 eligible studies, the pooled prevalence of treatment failure in HIV-infected women was 21.4% (95% confidence interval [CI] 15.8–27.0). There was no significant difference in the treatment failure prevalence for cryotherapy (13.9%, 95% CI 6.1–21.6) versus loop electrosurgical excision procedure (13.8%, 95% CI 8.9–18.7; P = .9), but the treatment failure prevalence was significantly higher in women with positive (47.2%, 95% CI 22.0–74.0) than with negative (19.4%, 95% CI 11.8–30.2) excision margin (OR 3.4, 95% CI 1.5–7.7). Treatment failure was significantly increased in HIV-infected versus HIV-uninfected women, both overall (OR 2.7, 95% CI 2.0–3.5) and in all sub-group analyses. Conclusions There is strong evidence for an increased risk of treatment failure in HIV-infected women, in comparison to their HIV-negative counterparts. The only significant predictor of treatment failure in HIV-infected women was a positive margin status, but further data is needed on long-term outcomes after ablative treatment in HIV-infected women.


2015 ◽  
Vol 143 (3) ◽  
pp. 344-351 ◽  
Author(s):  
Hye-Young Wang ◽  
Sunyoung Park ◽  
Sunghyun Kim ◽  
Dongsup Lee ◽  
Geehyuk Kim ◽  
...  

2017 ◽  
Vol 1 (1) ◽  
pp. 6
Author(s):  
Miftakh Nur Rahman ◽  
Chyntia Resti Wijaya ◽  
Maria Novalentina

Cervical cancer is the primary lethal malignancy for women worldwide, but because it develops over time, it would be one of the most preventable types of cancer. Dysregulation of apoptosis in cells plays a critical role in the malignancy development. Survivin is the smallest inhibitor apoptotic protein (IAP) which has an important part in regulating cell division and inhibitor of apoptosis. This review focused on survivin features in cervical cancer from mechanisms of malignancy relationship to human papillomavirus (HPV) infection through E6 oncogenic protein, role as a biomarker in diagnosis, prognosis, staging and prediction of metastasis, and also as a target for therapy. Regulation of survivin divided into two main groups; cell cycle dependent and cell cycle independent pathway to maintain life and death balance. Survivin expression is upregulated by E6 protein simultaneously repressing p53. Thus cancerous cervical tissue developed. Survivin is also upregulated in hypoxia, a common condition in many tumors and increased angiogenesis. Survivin plays a major role in chemotherapy and radiation resistance in many cases of cervical cancer. As a target of therapy, survivin has a promising performance, suggested very specific and no issue of resistance and also reducing resistance to chemo and radiation therapy. The goal of treatment is to lower survivin expression through transcription inhibition, immunotherapy based on cytotoxic T cell (CTL) activity and gene therapy.  Keywords: cervical cancer, survivin, HPV E6 oncoprotein, therapy


2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 33s-33s
Author(s):  
P. Gyawali ◽  
S.R. KC ◽  
S. Ghimire

Background: Age standardized cervical cancer incidence rate in Nepal is 19.2/100,000 woman, compared with 14.0 worldwide. Similarly, mortality rate is 12.0 women which is significant in comparison with 6.8 worldwide. Cervical intraepithelial neoplasm is a precursor lesion, having high transformation rate into the cervical carcinoma. Data clearly indicates that CIN 2 and 3 has more progression into cervical carcinoma. Despite the fact that Papanicolaou test has remained an important tool in the screening for cervical cancer and has contributed in significant decrease in cervical cancer, sensitivity and specificity of conventional Papanicolaou test is quite low. Colposcopy is visual inspection of cervix under magnification. Study revealed that the positive predictive rate of the colposcopic impression is better as the cervical lesion is more severe. Aim: To find out the significance of colposcopy in the detection of dysplastic cervical lesions and possible use of this method as a screening tool. Methods: This is an observational study done at Cancer Care Foundation, Nepal done from a period of January 2015 to February 2018. Permission was obtained from ethical committee and written consent was obtained from the patients. All the patients suspected having dysplastic or invasive lesions or in whom colposcopy-guided biopsy was performed; were included in the study. Relevant data were collected which included age, colposcopic diagnosis, histopathological diagnosis. Data were entered into Microsoft Excel and statistical analysis was done from statistical package SPSS 21. Results: 6109 females were screened through colposcopy. Out of these 900 patients underwent colposcopy-guided biopsy for being suspected of dysplastic lesions or inflammatory lesions. Mean age of females was 40.65 years. With colposcopy, 407 (45.2%) were suspected to have low grade lesion, followed by 401 (44.6%) high grade lesion and 15 (1.7%) carcinoma. Nonneoplastic lesions were suspected in 77 (8.6%) females. In the histopathological examination low grade dysplasia was observed in 403 (44.8%) followed by 250 (27.8%) high grade dysplasia and 8 (0.9%) carcinoma in-situ or invasive carcinoma. Similarly, 239 (26.6%) patients had nonneoplastic lesions. In colposcopy, high grade lesions were suspected more frequently in females of 41-50 years age group than in 31-40 years age group ( P < 0.01). Correlation between increasing age and dysplastic lesions were also observed ( P < 0.05). There was significant correlation between colposcopic diagnosis and histopathological diagnosis with a P value < 0.01. The sensitivity of colposcopy to diagnose dysplastic lesions were high 96.44% with positive predictive value of 62.65%. The specificity of colposcopy to diagnose various grades of dysplastic lesions is 34.98%. Conclusion: Colposcopy is highly sensitive method of screening dysplastic cervical lesions and should be used more frequently as a screening purpose.


2003 ◽  
Vol 89 (1) ◽  
pp. 101-105 ◽  
Author(s):  
G M Clifford ◽  
J S Smith ◽  
T Aguado ◽  
S Franceschi

2017 ◽  
Vol 139 (1) ◽  
pp. 90-94 ◽  
Author(s):  
Angela Pista ◽  
Carlos Freire de Oliveira ◽  
Carlos Lopes ◽  
Maria J. Cunha ◽  

2019 ◽  
Author(s):  
Awoke Derbie ◽  
Daniel Mekonnen ◽  
Yimtubeznash Woldeamanuel ◽  
Xaveer Van Ostade ◽  
Tamrat Abebe

Abstract Background: Genital infection with certain types of Human papillomavirus (HPV) is a major cause of cervical cancer globally. For early detection of premalignant dysplasia, evidences are coming out on the usefulness of HPV E6/E7 mRNA test as a potential tool compared with cytology and HPV DNA testing. Taking into account shortage of compiled data on this field, the aim of this systematic review was to describe the latest diagnostic performance of HPV E6/E7 mRNA testing to detect high grade cervical lesions (CIN2+) where by histology as was taken as a ‘gold standard’. Methods: Articles published in English were systematically searched using key words from PubMed/Medline and SCOPUS. In addition, Google Scholar and the Google database were searched manually for grey literature. Two reviewers independently assessed study eligibility, risk of bias and extracted the data. We performed a descriptive presentation of the performance of E6/E7 mRNA testings (interims of sensitivity, specificity, negative and positive predictive values) for the detection of CIN2+. Results: Out of 231 applicable citations, we have included 29 articles with a total of 23,576 study participants (age range, 15-84) who had different cervical pathologies. Among the participants who had cervical histology, the proportion of CIN2+ was between 10.6% and 90.6%. Using histology as a gold standard, 11 studies evaluated the PreTect HPV Proofer, 7 studies evaluated the APTIMA HPV assay (Gen-Probe) and 6 studies evaluated the Quantivirus® HPV assay. The diagnostic performance of those three most common mRNA testing tools to detect CIN2+ was; 1) PreTect Proofer; median sensitivity 83%, median specificity 73%, median PPV 70 and median NPV 88.9%. 2) APTIMA assay; median sensitivity 91.4%, median specificity 46.2%, median PPV 34.3% and median NPV 96.3%. 3) Quantivirus®: median sensitivity 86.1%, median specificity 54.6%, median PPV 54.3%, median NPV 89.3%. Further, the area under the receiver operating characteristics (AU-ROC) curve varied between 63.8% and 90.9%. Conclusions: The reported diagnostic accuracy implies that mRNA tests possess diagnostic relevance to detect CIN2+ and could potentially be considered in areas where there is no histology facility. Further studies including its cost should be considered.


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