Abstract B11: Viral and host gene methylation in liquid prep: novel molecular screening and triage tools to reduce cervical cancer disparities

Abstract Background This study aimed to determine whether ZNF582 gene methylation and tissue protein expression can be used as a tool with high sensitivity and specificity for cervical cancer screening. We analyzed the correlation between promoter methylation of the zinc finger protein 582 (ZNF582) gene and cervical cancer and high risk HPV16/18 infection. Methods Tissue samples of normal cervical or chronic cervicitis (n=51), CIN (cervical intraepithelial neoplasia) (n=35), and cervical carcinoma (n=68) were tested for HPV16/18 infection by polymerase chain reaction (PCR). We also detected the methylation status of the ZNF582 gene promoter in the same tissues by methylation specific PCR (MSP), then analyzed the correlation between ZNF582 promoter methylation and HPV16/18 infection. Immunohistochemistry was used to analyze ZNF582 gene expression in 152 cervical tissues. We detected ZNF582 mRNA expression in cervical tissues (including cancer and non-cancer) by real-time fluorescence quantitative PCR (qRT-PCR).Results Among 93 high grade cervical lesions (CINII and above) and cervical cancer samples, 57 cases were positive for HPV16/18 infection and 36 cases were negative. ZNF582 gene methylation occurred in 9 out of 51 cases in normal cervical tissues (17.6%), 16 of 35 cases in CIN tissues (45.7%), and 50 of 68 cases in cervical cancer (73.5%). The differences in methylation rate of the three groups were statistically significant (P<0.05). The ZNF582 methylation rate in the positive HPV16/18 infection group was 73.7%, while the negative group was 63.9%. Compared with normal tissues, ZNF582 protein was highly expressed in cervical cancer tissues, but mRNA expression was low.Conclusion While ZNF582 protein is highly expressed in cervical cancer tissues, it was not sufficient for use as a standard for cervical cancer staging. On the other hand, ZNF582 promoter methylation had high specificity and sensitivity in detecting CINII and highly diseased cervical lesions and could be used as a diagnostic marker for cervical cancer of women.

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Upregulation of Long Non-Coding RNA Small Nucleolar RNA Host Gene 12 Contributes to Cell Growth and Invasion in Cervical Cancer by Acting as a Sponge for MiR-424-5p

Cellular Physiology and Biochemistry ◽

10.1159/000488045 ◽

2018 ◽

Vol 45 (5) ◽

pp. 2086-2094 ◽

Cited By ~ 33

Author(s):

Jing Dong ◽

Qing Wang ◽

Li Li ◽

Zhang Xiao-jin

Keyword(s):

Cervical Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Host Gene ◽

Migration And Invasion ◽

Small Nucleolar Rna ◽

Cervical Cancer Cells ◽

Cancer Tissues ◽

Nucleolar Rna

Background/Aims: Cervical cancer, which is one of the most aggressive cancers affecting females, has high rates of recurrence and mortality. Small nucleolar RNA host gene 12 (SNHG12) is known to promote the progression of several cancers; however, its exact effects and molecular mechanisms in cervical cancer remain unknown. Methods: Real-time quantitative PCR was used to determine the expression level of SNHG12 in cervical cancer tissues and cell lines. Loss-of-function assays were performed to examine the effect of SNHG12 on the proliferation, apoptosis, migration and invasion of cervical cancer cells in vitro and tumor growth in vivo. Luciferase experiments were employed to explore the interactions between SNHG12 and miR-424-5p. Results: SNHG12 was found to be abnormally elevated in human cervical cancer tissues compared with paired adjacent normal tissues. Moreover, high SNHG12 expression in tumor tissues was significantly correlated with vascular involvement, lymph node metastasis, advanced FIGO stage and poor prognosis. Furthermore, the knockdown of SNHG12 was found to inhibit proliferation, migration and invasion of cervical cancer cells in vitro, and silencing SNHG12 was shown to suppress tumor growth in a nude mouse model. Mechanistic studies showed that SNHG12 functioned as an endogenous sponge for miR-424-5p, thereby downregulating the expression of miR-424-5p in cervical cancer. Furthermore, the inhibition of miR-424-5p in SNHG12-depleted cells partially reversed the effects on cervical cancer cell apoptosis, adhesion and invasion. Conclusion: In summary, our findings suggest that the tumor-promoting role of SNHG12 is to function as a molecular sponge, which negatively regulates miR-424-5p. These findings may provide a potent therapeutic target for cervical cancer.

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The application value of PAX1 and ZNF582 gene methylation in high grade intraepithelial lesion and cervical cancer

Clinical & Translational Oncology ◽

10.1007/s12094-020-02416-5 ◽

2020 ◽

Author(s):

H. Liang ◽

G. L. Li ◽

J. Liu ◽

M. Fu ◽

H. Huang ◽

...

Keyword(s):

Cervical Cancer ◽

High Grade ◽

Gene Methylation ◽

Intraepithelial Lesion

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The Intersection between Oral Microbiota, Host Gene Methylation and Patient Outcomes in Head and Neck Squamous Cell Carcinoma

Cancers ◽

10.3390/cancers12113425 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3425

Author(s):

Zigui Chen ◽

Po Yee Wong ◽

Cherrie W. K. Ng ◽

Linlin Lan ◽

Sherwood Fung ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Early Detection ◽

Patient Outcomes ◽

Host Gene ◽

Oral Microbiota ◽

Gene Methylation ◽

Normal Tissues ◽

Oral Rinse ◽

Tumor Tissues

The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of Fusobacterium and Peptostreptococcus in HNSCC tumor tissues when compared to the adjacent normal tissues, and in HNSCC oral rinses when compared to healthy subjects, while ten other bacterial genera were largely depleted. These HNSCC-related bacteria were discriminative for HNSCC and controls with area under the receiver operating curves (AUCs) of 0.84 and 0.86 in tissue and oral rinse samples, respectively. Moreover, Fusobacterium nucleatum abundance in HNSCC cases was strongly associated with non-smokers, lower tumor stage, lower rate of recurrence, and improved disease-specific survival. An integrative analysis identified that enrichment of F. nucleatum was associated with host gene promoter methylation, including hypermethylation of tumor suppressor genes LXN and SMARCA2, for which gene expressions were downregulated in the HNSCC cohort from The Cancer Genome Atlas. In conclusion, we identified a taxonomically defined microbial consortium associated with HNSCC that may have clinical potential regarding biomarkers for early detection or intervention. Host–microbe interactions between F. nucleatum enrichment and clinical outcomes or host gene methylation imply a potential role of F. nucleatum as a pro-inflammatory driver in initiating HNSCC without traditional risk factors, which warrants further investigation for the underlying mechanisms.

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Abstract IA12: Addressing cervical cancer disparities in Appalachia: From biology to policy

10.1158/1538-7755.disp15-ia12 ◽

2016 ◽

Author(s):

Electra D. Paskett

Keyword(s):

Cervical Cancer ◽

Cancer Disparities

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Abstract B008: South Carolina's National Breast and Cervical Cancer Early Detection Program narrows the gap in South Carolina breast cancer disparities

10.1158/1538-7755.disp18-b008 ◽

2020 ◽

Author(s):

Swann Arp Adams ◽

Samantha C. Truman ◽

Oluwole Babatunde ◽

Tisha M. Felder ◽

Jan M. Eberth ◽

...

Keyword(s):

Breast Cancer ◽

Cervical Cancer ◽

South Carolina ◽

Cancer Disparities ◽

Cancer Early Detection ◽

Breast And Cervical Cancer ◽

National Breast ◽

Detection Program ◽

Early Detection Program ◽

Breast Cancer Disparities

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A Multi-level Model to Understand Cervical Cancer Disparities in Appalachia

Cancer Prevention Research ◽

10.1158/1940-6207.capr-19-0239 ◽

2020 ◽

Vol 13 (3) ◽

pp. 223-228 ◽

Cited By ~ 3

Author(s):

Electra D. Paskett ◽

Michael L. Pennell ◽

Mack T. Ruffin ◽

Christopher M. Weghorst ◽

Bo Lu ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Disparities ◽

Level Model ◽

Multi Level

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PAX1 Methylation as a Potential Biomarker to Predict the Progression of Cervical Intraepithelial Neoplasia: A Meta-analysis of Related Studies

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001011 ◽

2017 ◽

Vol 27 (7) ◽

pp. 1480-1488 ◽

Cited By ~ 5

Author(s):

Ting Luan ◽

Quan Hua ◽

Xia Liu ◽

Pengfei Xu ◽

Yun Gu ◽

...

Keyword(s):

Cervical Cancer ◽

Cervical Intraepithelial Neoplasia ◽

Web Of Science ◽

Meta Analysis ◽

Great Influence ◽

Intraepithelial Neoplasia ◽

Cochrane Library ◽

Gene Methylation ◽

Potential Biomarker ◽

Number Of Patients

ObjectiveThe methylation of paired box gene 1 (PAX1) has a great influence on the process of cervical lesion. However, available evidence for the association between PAX1 methylation and cervical intraepithelial neoplasia (CIN) are inconsistent. Here, we systematically reviewed and analyzed PAX1 methylation in progress of CIN.MethodsTwo investigators independently searched eligible studies of PAX1 methylation and CIN that were published in PubMed, Cochrane Library, EMBASE, and Web of Science databases until November 30, 2016. We extracted clinicopathologic features of CIN and cervical cancel relevant to PAX1 methylation. Odds ratios (ORs) with their 95% confidence intervals (CIs) were used to assess the association between PAX1 methylation and progression of patients with CIN.ResultsSeven studies composed of 1055 patients with various stages of CIN and cervical cancel were eventually included. The results revealed that PAX1 methylation was associated with transition of CIN I to CIN II/III (OR, 0.09; 95% CI, 0.04–0.19) and CIN II/III to cervical cancer (OR, 0.16; 95% CI, 0.05–0.46), and similar results were produced in sensitivity analysis. Also, we found that the OR value was associated with average age and number of patients, publication year, and study location of included articles.ConclusionsPAX1 gene methylation was associated with the transition of CIN I to CIN II/III and CIN II/III to cervical cancer, so that it could be an auxiliary biomarker to estimate the risk of CIN progress. Moreover, PAX1 may help to determine appropriate reexaminations and treatment for patients with various stages of CIN.

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