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Concomitant underexpression of TGFBR2 and overexpression of hTERT are associated with poor prognosis in cervical cancer

Yang, Hui ; Zhang, Hongyan ; Zhong, Yahua ; Wang, Qiaoli LU orcid ; Yang, Lei ; Kang, Hong ; Gao, Xiaojia ; Yu, Haijun ; Xie, Conghua and Zhou, Fuxiang , et al. (2017) In Scientific Reports 7.
Abstract

The human telomerase reverse transcriptase (hTERT) is highly expressed in a variety of tumors. The transforming growth factor beta receptor type II (TGFBR2) is a downstream protein of transforming growth factor beta (TGF-β) which suppresses telomerase activity. However, the relevance of survival to the expression of TGFBR2, hTERT or TGFBR2/hTERT has not been previously investigated in cervical cancer tissues. Our study showed that patients with low level of TGFBR2 were associated with poor prognosis (HR = 1.704, P = 0.021), but no significant relevance between hTERT expression and survival (HR = 1.390, P = 0.181). However, a combination of low level of TGFBR2 and high level of hTERT was associated with a worse survival (HR = 1.892, P =... (More)

The human telomerase reverse transcriptase (hTERT) is highly expressed in a variety of tumors. The transforming growth factor beta receptor type II (TGFBR2) is a downstream protein of transforming growth factor beta (TGF-β) which suppresses telomerase activity. However, the relevance of survival to the expression of TGFBR2, hTERT or TGFBR2/hTERT has not been previously investigated in cervical cancer tissues. Our study showed that patients with low level of TGFBR2 were associated with poor prognosis (HR = 1.704, P = 0.021), but no significant relevance between hTERT expression and survival (HR = 1.390, P = 0.181). However, a combination of low level of TGFBR2 and high level of hTERT was associated with a worse survival (HR = 1.892, P = 0.020), which had higher impact of hazard ratio (HR) on the overall survival (OS) than the low TGFBR2 expression alone. Knockdown of TGFBR2 expression by shRNA in Hela cells increased cell proliferation, cell invasion, G1/S transition and telomere homeostasis but decreased cell apoptosis. Overexpressing TGFBR2 and inhibiting hTERT suppressed Hela cell growth. These results would lead us to further explore whether a phenotype of TGFBR2low/hTERThigh could be considered as a predictor of poor prognosis, and whether simultaneous use of TGFBR2 agonist and hTERT inhibitor could be developed as a therapeutic strategy.

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publishing date
type
Contribution to journal
publication status
published
keywords
Adult, Aged, Apoptosis/genetics, Biomarkers, Tumor, Cell Cycle/genetics, Cell Line, Tumor, Cell Proliferation, Disease Progression, Female, Gene Expression Regulation, Neoplastic, HeLa Cells, Humans, Immunohistochemistry, Middle Aged, Neoplasm Grading, Neoplasm Metastasis, Neoplasm Staging, Prognosis, Protein Serine-Threonine Kinases/genetics, ROC Curve, Receptor, Transforming Growth Factor-beta Type II, Receptors, Transforming Growth Factor beta/genetics, Risk Factors, Telomerase/genetics, Telomere/genetics, Tissue Array Analysis, Uterine Cervical Neoplasms/genetics
in
Scientific Reports
volume
7
article number
41670
publisher
Nature Publishing Group
external identifiers
  • scopus:85012299423
  • pmid:28195144
ISSN
2045-2322
DOI
10.1038/srep41670
language
English
LU publication?
no
id
2b8ec4c8-6760-4e29-bb46-b4e635e6a729
date added to LUP
2025-05-12 16:58:40
date last changed
2025-05-27 06:15:19
@article{2b8ec4c8-6760-4e29-bb46-b4e635e6a729,
  abstract     = {{<p>The human telomerase reverse transcriptase (hTERT) is highly expressed in a variety of tumors. The transforming growth factor beta receptor type II (TGFBR2) is a downstream protein of transforming growth factor beta (TGF-β) which suppresses telomerase activity. However, the relevance of survival to the expression of TGFBR2, hTERT or TGFBR2/hTERT has not been previously investigated in cervical cancer tissues. Our study showed that patients with low level of TGFBR2 were associated with poor prognosis (HR = 1.704, P = 0.021), but no significant relevance between hTERT expression and survival (HR = 1.390, P = 0.181). However, a combination of low level of TGFBR2 and high level of hTERT was associated with a worse survival (HR = 1.892, P = 0.020), which had higher impact of hazard ratio (HR) on the overall survival (OS) than the low TGFBR2 expression alone. Knockdown of TGFBR2 expression by shRNA in Hela cells increased cell proliferation, cell invasion, G1/S transition and telomere homeostasis but decreased cell apoptosis. Overexpressing TGFBR2 and inhibiting hTERT suppressed Hela cell growth. These results would lead us to further explore whether a phenotype of TGFBR2low/hTERThigh could be considered as a predictor of poor prognosis, and whether simultaneous use of TGFBR2 agonist and hTERT inhibitor could be developed as a therapeutic strategy.</p>}},
  author       = {{Yang, Hui and Zhang, Hongyan and Zhong, Yahua and Wang, Qiaoli and Yang, Lei and Kang, Hong and Gao, Xiaojia and Yu, Haijun and Xie, Conghua and Zhou, Fuxiang and Zhou, Yunfeng}},
  issn         = {{2045-2322}},
  keywords     = {{Adult; Aged; Apoptosis/genetics; Biomarkers, Tumor; Cell Cycle/genetics; Cell Line, Tumor; Cell Proliferation; Disease Progression; Female; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Immunohistochemistry; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Protein Serine-Threonine Kinases/genetics; ROC Curve; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta/genetics; Risk Factors; Telomerase/genetics; Telomere/genetics; Tissue Array Analysis; Uterine Cervical Neoplasms/genetics}},
  language     = {{eng}},
  month        = {{02}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Concomitant underexpression of TGFBR2 and overexpression of hTERT are associated with poor prognosis in cervical cancer}},
  url          = {{http://dx.doi.org/10.1038/srep41670}},
  doi          = {{10.1038/srep41670}},
  volume       = {{7}},
  year         = {{2017}},
}