title: Concomitant underexpression of TGFBR2 and overexpression of hTERT are associated with poor prognosis in cervical cancer.
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 = 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/hTERThighcould 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.
authors.affiliation: Hubei Key Laboratory of Tumor Biological Behavior, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Hubei Key Laboratory of Tumor Biological Behavior, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China.|Department of Radiation Oncology &Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, P.R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Hubei Key Laboratory of Tumor Biological Behavior, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China.|Department of Radiation Oncology &Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, P.R. China.
authors.forename: Yahua
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Hubei Key Laboratory of Tumor Biological Behavior, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Hubei Key Laboratory of Tumor Biological Behavior, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China.|Department of Radiation Oncology &Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Hubei Key Laboratory of Tumor Biological Behavior, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Kang
authors.affiliation: Hubei Key Laboratory of Tumor Biological Behavior, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Gao
authors.affiliation: Hubei Key Laboratory of Tumor Biological Behavior, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China.|Department of Radiation Oncology &Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, P.R. China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.affiliation: Hubei Key Laboratory of Tumor Biological Behavior, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China.|Department of Radiation Oncology &Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, P.R. China.
authors.forename: Conghua
authors.initials: C
authors.lastname: Xie
authors.affiliation: Hubei Key Laboratory of Tumor Biological Behavior, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China.|Department of Radiation Oncology &Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, P.R. China.
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Hubei Key Laboratory of Tumor Biological Behavior, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China.|Department of Radiation Oncology &Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, P.R. China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012372:ROC Curve; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000235:genetics; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; C509186:TERT protein, human; D019098:Telomerase