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Distribution of HPV16 E6 295T/G and E7 647A/G variants in cervical cancer and effects on IFNκ and its pathway
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  • Zemin Pan,
  • Binxuan Guo,
  • Le Wang,
  • Xian Zhao,
  • Xiangyi Zhe,
  • Jing Tuo,
  • Dongmei Li,
  • Hongtao Li,
  • Renfu Shao
Zemin Pan
Shihezi University

Corresponding Author:[email protected]

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Binxuan Guo
Shihezi University
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Le Wang
Shihezi University
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Xian Zhao
Shihezi University
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Xiangyi Zhe
Shihezi University
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Jing Tuo
Shihezi University
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Dongmei Li
Shihezi University
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Hongtao Li
Shihezi University
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Renfu Shao
University of the Sunshine Coast School of Science Technology and Engineering
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Abstract

Objective: To investigate the distribution characteristics of HPV16 E6 gene 295T/G and E7 gene 647A/G variants in different cervical tissues in Xinjiang, to study the effects of these two loci on the expression of molecules in IFNκ and its pathway, to explore the molecular mechanism of their roles, and to analyse the relationship between these two variants and the occurrence and development of cervical cancer. Methods: (1) A total of 461 cervical paraffin-embedded tissue samples were collected and tissue DNA was extracted to detect the type of HPV infection by PCR, and the distribution of HPV16 viral E6-T295G and E7-A647G variants in cervical tissues was analysed by Sanger sequencing. Immunohistochemistry was used to detect the expression of IFNκ and molecules on its pathway including IFNκ, STAT1, IRF9, IFI27, IFI44L,OAS1 in cervical cancer and normal cervical tissues. Results: (1) The HPV16 infection rate of cervical paraffin-embedded tissue samples from women in Xinjiang region was 64.0% by PCR. And the HPV16 infection rate of Uyghur was 75.7%, of which the infection rate of Uyghur CIN1 and CIN2 with HPV16 was 60.6%, and the infection rate of CIN3 and cervical cancer was 82.9%. The HPV16 infection rate of Han ethnic group was 54.5%, among which the infection rate of Han ethnic group CIN1 and CIN2 of HPV16 was 34.0%, and the infection rate of CIN3 and cervical cancer was 66.5%. (2) The variant rate of Uyghur CIN1 patients presenting with E6-295T/G variant was 41.7%, and the variant rate of squamous cervical cancer patients presenting with E6-295T/G variant was 43.4%. The variant rate of Han ethnic group CIN1 patients presenting with the E6-295T/G variant was 33.3%, and the variant rate of squamous cervical cancer patients presenting with the E6-295T/G variant was 16.1%. The variant rate of Uyghur CIN1 patients presenting with the E7-647A/G variant was 41.7%, and the variant rate of squamous cervical cancer patients presenting with the E7-647A/G variant was 9.2%. The variant rate of E7-647A/G variant was 45.8% in Han ethnic group of CIN1 patients and 50.0% in squamous cervical cancer patients. (3) The results showed that the expression of IFNκ, IRF9, OAS1, IFI27, and IFI44L molecules on the IFNκ pathway was higher in normal cervical tissues uninfected with HPV than that of CIN1 with HPV infection, and the difference was statistically significant ( P<0.05). The expression of IFNκ, STAT1, IRF9, OAS1, IFI27, IFI44L molecules in CIN3, moderately differentiated, poorly differentiated cervical squamous carcinoma and adenocarcinoma were higher than that of CIN1, and the molecular expression of IFN-κ and its pathway in cervical squamous cell carcinoma and adenocarcinoma was higher than that in normal tissues, and the difference was statistically significant ( P<0.05). Conclusion: The rate of E6-295T/G variation in cervical cancer patients infected with HPV16 in Uyghur is higher than that in Han, while the rate of E7-647A/G variation in cervical cancer patients infected with HPV16 in Han is higher than that in Uyghur.
27 Mar 2024Submitted to Journal of Medical Virology
28 Mar 2024Submission Checks Completed
28 Mar 2024Assigned to Editor
28 Mar 2024Review(s) Completed, Editorial Evaluation Pending
30 Mar 2024Reviewer(s) Assigned
29 Jun 2024Editorial Decision: Revise Major
14 Nov 20241st Revision Received
15 Nov 2024Submission Checks Completed
15 Nov 2024Assigned to Editor
15 Nov 2024Review(s) Completed, Editorial Evaluation Pending
21 Nov 2024Reviewer(s) Assigned