Relevance research between the expression of p16INK4a , Notch1, and hTERC genes: The development of HPV16-positive cervical cancer.

BACKGROUND: GLOBOCAN 2018 latest data show cervical cancer ranks fourth in morbidity and mortality among women. Many genes in cervical lesions differ in sensitivity and specificity. However, the diagnostic molecules for early cervical cancer are not very clear. This paper screens biomarkers for early molecular diagnosis of Mongolian patients with cervical cancer. METHODS: Immunohistochemical SP method was used to detect the expression of p16INK4a and Notch1 protein in paraffin sections of 226 Mongolian patients with HPV16-positive cervical lesions after pathological examination, and 100 of them were randomly selected by fluorescence in situ hybridization to detect hTERC gene. The HPV16-binding human cervical cancer SiHa cell line was used to silence the expression of HPV16 E6/E7 gene by RNA interference, and the expression of p16INK4a , Notch1, and hTERC genes and protein expression levels were detected by RT-PCR and Western blot. RESULTS: The positive expression rates of p16INK4a , Notch1, and hTERC genes in HPV16-positive cervical cancer, CIN-III, CIN-II, CIN-I, uterine leiomyoma, and chronic cervicitis were significantly different (P < .05); the positive expression rates of the three genes were also significantly different in the same type of cervical lesions (P < .05); RNA interference can effectively inhibit HPV16 E6/E7, p16INK4a and Notch1 gene expression, but has no effect on hTERC gene expression. CONCLUSION: The p16INK4a gene can be used as a biomarker for early screening of cervical cancer, and the hTERC gene can be used to confirm the clinical diagnosis of cervical cancer.

Diagnostic value of hTERC gene expression in cervical intraepithelial neoplasia in gynecologic cytology / 肿瘤研究与临床

Objective To investigate the expression of human telomerase RNA component (hTERC)gene in cervical scraping samples, and the relationship between hTERC gene and cervical lesions. Methods The fluorescent in situ hybridization (FISH) was used to detect the expression of hTERC oncogene in cervical scraping samples in 100 cases, including 76 cases with cervical intraepithelial neoplasia, meanwhile, high risk human papillomavirus (HR-HPV) were detected by Hybrid Capture 2 (HC2) . The other 24 cases were negative for intraepithelial lesion (NILM). Results The positive expression rates of the hTERC gene in NILM,ASCUS, ASC-H, LSIL, HSIL and cervical cancer were 0, 32.25 %, 75.00 %, 35.71 %, 81.81 % and 100.00 % respectively. hTERC gene positive expression in normal group was less significantly than that in abnormal groups (P <0.05). There was a significantly difference between HSIL and ASCUS, LSIL (x2 = 6.1736, x2 =5.0004, P <0.05). The positive expression rates of the HR-HPV in ASCUS, ASC-H, LSIL and HSIL or higher lesions were 54.80 %, 75.00 %, 60.70 %, 90.90 % and 100.00 % respectively. HR-HPV positive expression in HSIL or higher lesions were more significantly than that in ASCUS group (x2=4.1767, P<0.05). Conclusion The overexpression of hTERC gene may play an important role in cervical carcinogenesis, therefore it can be used as a better tumor marker for prospective in early cervical cancer progresses.

Relationship of human telomerase mRNA component gene expression in cervical exfoliated cells with cervical lesions and human papilloma virus infection / 第二军医大学学报

Objective: To explore the relationship of human telomerase mRNA component gene (hTERC) expression with the degree of cervical lesions and the infection of different genotypes of human papilloma virus(HPV). Methods: The thinprep cytologic test (TCT) specimens from 34 pathologically confirmed cervical intraepithelial neoplasia (CIN, including 8 CIN I, 9. CIN II, 17 CIN III), 36 invasive squamous cervical carcinoma (ISCC), and 20 chronic cervicitis patients were included in the present study. HPV subtype infection was detected by channelization hybridization gene chip and hTERC expression was tested by fluorescence in situ hybridization(FISH). The relationship between hTERC expression, the degree of cervical lesions and the infection with HPV was analyzed. Results: The positive rates of hTERC in chronic cervicitis, CIN I, CIN II, CIN III, and ISCC specimens were 0.00% (0/20), 50. 00% (4/8), 77.78% (7/9), 82.35% (14/17), and 97.22% (35/36), respectively. The positive rates of hTERC increased with the increase of cervical lesion degree, and there were significant differences between the three subgroups(P<0.05). The HPV infection rates were 10.00% (2/20), 37.50% (3/8), 66.67% (6/9), 88.24% (15/17), and 91.67% (33/36), respectively. The positive rates of hTERC in HPV16 type-positive, other high-risk type positive and negative/low-risk type positive groups were 90.38% (47/52), 66.67% (4/6), and 28.13% (9/32), respectively, with significant difference found between each two groups (P<0.01). Conclusion: The progress of cervical lesions and HPV infection are closely related to the positive rates of hTERC. HPV16 infection is the main cause for the high-level cervical lesions, and HPV58, 33, 52 have some advantages in CIN or ISCC.

Clinical Significance of hTERC Gene Amplification Detection by FISH in the Screening of Cervical Lesions / 华中科技大学学报（医学）（英德文版）

adjunct to cytology screening, especially high-risk patients.

Predictive Value of Detection of hTERC Gene Copy Number in Cervical Epithelial Cells by means of Fluorescence in situ Hybridization and Human Papilloma Virus Testing for Cervical Intraepithelial Neoplasia / 中华医院感染学杂志

OBJECTIVE To explore the predictive value of human telomerase RNA gene component(hTERC) gene amplification and high-risk human papilomavirus(HR-HPV) testing in cervical intraepithelial neoplasia(CIN) as a marker for early diagnosis of cervix carcinoma.METHODS Fluorescence in situ hybridization(FISH) was used to detect the amplification of hTERC of cervical epithelial cells in 72 cases.By using hybrid capture 2(HC-2),two types of the HR-HPV DNA(HPV16/18) of each case were detected.Then,the results were compared with the pathologic diagnosis.The dual-color probe we used was GLP TERC/CSP 3.HeLa cells and lymphocytes from normal marrow were the positive control,while the cervical specimens from healthy outpatients were the negative control.RESULTS hTERC Gene amplification of specimens was tested in 72 cases,the positive amplification rate of hTERC gene in the cervicitis/CINⅠgroup and normal,compared to the cervical carcinomas(100%) and CIN Ⅱ/Ⅲ(68.75%),which showed a significant difference.The rates in CINⅡ and CINⅢ were 60.00% and 83.33%,respectively,which showed a significant difference compared with normal and CINⅠ/inflammation groups.hTERC gene amplification was positive in both HeLa cells and lymphocytes from normal marrow and HC-2 testing was positive in 32 cases of patients containing 11 cases of CINⅡ/Ⅲ,3 cases of cervical cancer,18 cases of cervicitis/CIN1 diagnosed.The positive predictive value(PPV) and specificity(Sp) of hTERC for the high-grade CIN was significantly higher than the PPV and Sp of HC-2 HR-HPV testing.CONCLUSIONS hTERC Gene involves in the progression and occurrence of cervical intraepithelial neoplasia and cervical squamous carcinoma.As a marker for early diagnosis of cervical intraepithelial neoplasia and cervical squamous carcinoma,the FISH method for hTERC gene is more reliable to differentiate the malignant diseases from the benign ones in cervixes than HC-2 HR-HPV DNA testing.The combined detection of HR-HPV and hTERC gene will provide more effective and suitable management to enhance the early diagnosis rate of cervical intraepithelial neoplasia and cervical squamous carcinoma.