&lt;b&gt;&lt;i&gt;c-myc&lt;/i&gt;&lt;/b&gt; Gene Copy Number Variation in Cervical Exfoliated Cells Detected on Fluorescence in situ Hybridization for Cervical Cancer Screening

Zhao, Weihong; Hao, Min; Cheng, Xiaotong; Yang, Xin; Wang, Zhi-lian; Cheng, Ke-Yan; Liu, Fangli; Bai, Yao-Xian

doi:10.1159/000442286

Cited by 7 publications

(11 citation statements)

References 27 publications

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“…Although loop electrosurgical excision (LEEP) procedures can be performed on LSIL patients to avoid LSIL progression, this treatment can be considered excessive in addition to causing an economic burden on the healthcare system (5). Therefore, it is of medical and economical relevance to identify biomarkers that can distinguish patients with LSIL that are at high risk of progressing into HSIL and cervical cancer (6,7).…”

Section: Introductionmentioning

confidence: 99%

Predictive value of p16INK4a, Ki‑67 and ProExC immuno‑qualitative features in LSIL progression into HSIL

et al. 2020

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The current nested case-control study was conducted to explore the prognostic value of cyclin-dependent kinase inhibitor 2A (p16 INK4a), marker of proliferation Ki-67 (Ki-67) and immunohistochemical cocktail containing antibodies directed against topoisomerase IIα (TOP2A) and minichromosome maintenance 2 (MCM2) proteins (ProExC) immuno-qualitative features to predict low-grade squamous intraepithelial lesion (LSIL) progression. A total of 92 LSIL patients were followed-up for 2 years, where those with high-grade squamous intraepithelial lesion (HSIL) or persistent LSIL were designated as the case group and those who spontaneously regressed were designated as the control group. The infection status of human papillomavirus (HPV) was evaluated using flow-through hybridization and gene chip, whilst the expression of p16 INK4a , Ki-67 and ProExC were tested in LSIL patient biopsies by immunohistochemistry. All data were collected at the beginning of the follow-up and patient outcomes were diagnosed by histopathological examination. To analyze the risk factors for LSIL progression, sensitivity, specificity, positive-negative predictive value (PPV-NPV), positive-negative likelihood ratio (PLR-NLR), Youden's index (YI) and multinomial logistic regression analysis was performed. The expression rates of p16 INK4a , Ki-67, and ProExC were found to be higher in the progression group compared with those in the persistence and regression groups. Only p16 INK4a expression significantly associated with high-risk HPV infection. With respect to predicting HSIL, p16 INK4a staining was the most sensitive but Ki-67 staining was found to be the most specific. YI was the highest (42.1%) for p16 INK4a expression in the present study, followed by ProExC (39.5%) and Ki-67 (28.3%). However, the expression of ProExC was found to be an independent risk factor for LSIL progression into HSIL. In conclusion, whilst immunohistochemical staining for p16 INK4a , Ki-67, and ProExC can be used to predict HSIL progression, only ProExC expression can be applied an independent risk factor for LSIL progression.

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Section: Introductionmentioning

confidence: 99%

Predictive value of p16INK4a, Ki‑67 and ProExC immuno‑qualitative features in LSIL progression into HSIL

et al. 2020

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“…Therefore, c-MYC may also be an important oncogene involved in tumor progression, and hence may be a potential biomarker for cervical cancer (17). Previously, there have been studies to evaluate the diagnostic value of h-TERC (18) or c-MYC (19) alone in TCT and HPV, or a combination of h-TERC and c-MYC (11) in CIN and cancer. However, limited studies have been performed in order to determine which is the most efficient and practical method based on the four tests (TCT, HPV DNA, h-TERC and c-MYC) (8).…”

Section: Introductionmentioning

confidence: 99%

“…However, limited studies have been performed in order to determine which is the most efficient and practical method based on the four tests (TCT, HPV DNA, h-TERC and c-MYC) (8). Additionally, the majority of studies are aimed at demonstrating the sensitivity and specificity of the aforementioned biomarkers in distinguishing high-grade cervical lesions (>CIN2 + or ≥CIN2) and invasive cancer types from low-grade lesions (11,18,19); consequently, studies rarely focus on the difference between normal and all precursor lesions as well as ICC. Furthermore, the conclusions remain inconsistent between different studies.…”

Section: Introductionmentioning

confidence: 99%

Genomic amplification of HPV, h‑TERC and c‑MYC in liquid‑based cytological specimens for screening of cervical intraepithelial neoplasia and cancer

Lou

Hong

et al. 2018

Oncol Lett

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Cervical cancer is one of the most prevalent female cancer types in developing countries. ThinPrep cytological test (TCT) and human papillomavirus (HPV) detection are canonical screening methods for cervical cancer currently. However, there are limitations to these techniques. The aim of the present study was to identify efficient and practical methods for the screening of cervical intraepithelial neoplasia (CIN) and carcinoma. Residual PreservCyt specimens were obtained from 1,000 women who were admitted between August 2013 and December 2015. TCT, human telomerase RNA component (h-TERC) fluorescent in situ hybridization (FISH), MYC-specific FISH and surface plasmon resonance (SPR)-HPV genotyping were performed, followed by histopathology for those patients with positive results in any of the four tests. As a result, 106, 64, 56 and 112 patients were positive in the TCT, h-TERC, c-MYC and SPR-HPV tests, respectively, resulting in 213 being scheduled for histopathology; inflammation was identified in 159 patients, CIN I in 31, CIN II in 14, CIN III in seven and invasive cervical cancer in two patients. Using histopathology as the gold standard, TCT exhibited the highest sensitivity (87.04%), while h-TERC analysis had the highest specificity (81.76%). Parallel tests demonstrated that the Youden's index of TCT + h-TERC was the highest (0.49), while the serial analysis reported that TCT + HPV had the highest Youden's index (0.53) compared with any of the biomarkers alone (TCT, 0.50; HPV, 0.29; h-TERC, 0.47). In conclusion, dual positive TCT and HPV may be an efficient approach for basic screening of cervical lesions. h-TERC amplification may serve as an auxiliary test to improve the specificity.

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“…Protooncogenes such as c-Myc direct changes in metabolism and protein synthesis supporting enhanced proliferation rates. The gene copy number gain of c-Myc was significantly higher in the cervical lesion of advanced histologic grade [ 33 , 34 ]. In our research, c-Myc expression dropped in cervical cancer cells as a result of IFN α -overexpressing MSC treatment, while neither p53 nor bcl-2 is related.…”

Section: Discussionmentioning

confidence: 99%

IFNα-Expressing Amniotic Fluid-Derived Mesenchymal Stem Cells Migrate to and Suppress HeLa Cell-Derived Tumors in a Mouse Model

Zhou

Tian

Wang

et al. 2018

Stem Cells International

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Background Immunotherapy for cervical cancer with type I interferon (IFN) is limited because of the cytotoxicity that accompanies the high doses that are administered. In this study, we investigated the utilization of amniotic fluid-derived mesenchymal stem cells (AF-MSCs) as a means for delivering IFNα to local tumor sites for the suppression of cervical cancer in a mouse model using HeLa cell xenografts. Methods The tumor tropism ability of AF-MSCs and AF-MSCs genetically modified to overexpress IFNα (IFNα-AF-MSCs) was examined through Transwell in vitro and through fluorescent images and immunohistochemistry in a mouse model. Tumor size and tumor apoptosis were observed to evaluate the efficacy of the targeting therapy. Mechanistically, tumor cell apoptosis was detected by cytometry and TUNEL, and oncogenic proteins c-Myc, p53, and Bcl-2 as well as microvessel density were detected by immunohistochemistry. Results In this model, intravenously injected AF-MSCs selectively migrated to the tumor sites, participated in tumor construction, and promoted tumor growth. After being genetically modified to overexpress IFNα, the IFNα-AF-MSCs maintained their tumor tropism but could significantly suppress tumor growth. The restrictive efficacy of IFNα-AF-MSCs was associated with the suppression of angiogenesis, inhibition of tumor cell proliferation, and induction of apoptosis in tumor cells. Neither AF-MSCs nor IFNα-AF-MSCs trigger tumor formation. Conclusions IFNα-AF-MSC-based therapy is feasible and shows potential for treating cervical cancer, suggesting that AF-MSCs may be promising vehicles for delivering targeted anticancer therapy.

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<b><i>c-myc</i></b> Gene Copy Number Variation in Cervical Exfoliated Cells Detected on Fluorescence in situ Hybridization for Cervical Cancer Screening

Cited by 7 publications

References 27 publications

Predictive value of p16INK4a, Ki‑67 and ProExC immuno‑qualitative features in LSIL progression into HSIL

Predictive value of p16INK4a, Ki‑67 and ProExC immuno‑qualitative features in LSIL progression into HSIL

Genomic amplification of HPV, h‑TERC and c‑MYC in liquid‑based cytological specimens for screening of cervical intraepithelial neoplasia and cancer

IFNα-Expressing Amniotic Fluid-Derived Mesenchymal Stem Cells Migrate to and Suppress HeLa Cell-Derived Tumors in a Mouse Model

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