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TPP1 is associated with risk of advanced precursors and cervical cancer survival

Wang, Qiao-Li LU orcid ; Gong, Caifeng ; Meng, Xiang-Yu ; Fu, Min ; Yang, Hui ; Zhou, Fuxiang ; Wu, Qiuji and Zhou, Yunfeng (2024) In PLoS ONE 19(5).
Abstract

It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003-2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We... (More)

It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003-2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We further analyzed the impact of TPP1 expression on the overall survival of cervical cancer patients by calculating the hazard ratio (HR) with 95% confidence intervals (CIs) using the multivariable-adjusted Cox regression model. Compared to the normal cervix, high TPP1expression was significantly associated with CIN 3 and cervical cancers (P<0.001 for both). Expressions of TPP1 and hTERT were highly correlated in CIN 3 (Kappa statistics = 0.50, P = 0.005), squamous cell carcinoma (Kappa statistics = 0.22, P = 0.011), and adenocarcinoma/adenosquamous carcinoma (Kappa statistics = 0.77, P = 0.001). Mechanistically, knockdown of TPP1 inhibited the expression of hTERT in both mRNA and protein levels. High expression of TPP1 (HR = 2.61, 95% CI 1.23-5.51) and co-high expression of TPP1 and hTERT (HR = 2.38, 95% CI 1.28-4.43) were independently associated with worse survival in cervical cancer patients. TPP1 and hTERT expression was correlated and high expression of TPP1 was associated with high risk of CIN 3 and cervical cancer and could predict a worse survival in cervical cancer.

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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Adult, Female, Humans, Middle Aged, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Shelterin Complex, Telomerase/genetics, Telomere-Binding Proteins/metabolism, Uterine Cervical Dysplasia/genetics, Uterine Cervical Neoplasms/genetics
in
PLoS ONE
volume
19
issue
5
article number
e0298118
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:38722833
  • scopus:85192850416
ISSN
1932-6203
DOI
10.1371/journal.pone.0298118
language
English
LU publication?
no
additional info
Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
id
c0d1fb28-ae59-40bc-a7ad-3d46f7c6858c
date added to LUP
2025-05-12 17:12:47
date last changed
2025-07-08 09:54:03
@article{c0d1fb28-ae59-40bc-a7ad-3d46f7c6858c,
  abstract     = {{<p>It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003-2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We further analyzed the impact of TPP1 expression on the overall survival of cervical cancer patients by calculating the hazard ratio (HR) with 95% confidence intervals (CIs) using the multivariable-adjusted Cox regression model. Compared to the normal cervix, high TPP1expression was significantly associated with CIN 3 and cervical cancers (P&lt;0.001 for both). Expressions of TPP1 and hTERT were highly correlated in CIN 3 (Kappa statistics = 0.50, P = 0.005), squamous cell carcinoma (Kappa statistics = 0.22, P = 0.011), and adenocarcinoma/adenosquamous carcinoma (Kappa statistics = 0.77, P = 0.001). Mechanistically, knockdown of TPP1 inhibited the expression of hTERT in both mRNA and protein levels. High expression of TPP1 (HR = 2.61, 95% CI 1.23-5.51) and co-high expression of TPP1 and hTERT (HR = 2.38, 95% CI 1.28-4.43) were independently associated with worse survival in cervical cancer patients. TPP1 and hTERT expression was correlated and high expression of TPP1 was associated with high risk of CIN 3 and cervical cancer and could predict a worse survival in cervical cancer.</p>}},
  author       = {{Wang, Qiao-Li and Gong, Caifeng and Meng, Xiang-Yu and Fu, Min and Yang, Hui and Zhou, Fuxiang and Wu, Qiuji and Zhou, Yunfeng}},
  issn         = {{1932-6203}},
  keywords     = {{Adult; Female; Humans; Middle Aged; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Shelterin Complex; Telomerase/genetics; Telomere-Binding Proteins/metabolism; Uterine Cervical Dysplasia/genetics; Uterine Cervical Neoplasms/genetics}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{TPP1 is associated with risk of advanced precursors and cervical cancer survival}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0298118}},
  doi          = {{10.1371/journal.pone.0298118}},
  volume       = {{19}},
  year         = {{2024}},
}