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

• Published in: PloS one Vol. 19; no. 5; p. e0298118
• Main Authors: Wang, Qiao-Li, Gong, Caifeng, Meng, Xiang-Yu, Fu, Min, Yang, Hui, Zhou, Fuxiang, Wu, Qiuji, Zhou, Yunfeng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.05.2024; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Adenosquamous; Adult; Binding proteins; Biology and Life Sciences; Biomarkers; Cancer; Cell Line, Tumor; Cervical cancer; Cervix; Confidence intervals; Correlation; Datasets; Development and progression; Ethylenediaminetetraacetic acid; Female; Gastric cancer; Gene expression; Gene Expression Regulation, Neoplastic; Hospitals; Humans; Immunohistochemistry; Impact analysis; Liver cancer; Medical prognosis; Medical records; Medicine and Health Sciences; Middle Aged; Oncology, Experimental; Pathogenesis; Patients; Physiological aspects; Polymerase chain reaction; Protein arrays; Protein binding; Protein expression; Proteins; Radiation therapy; Real time; Regression models; Research and Analysis Methods; Risk factors; RNA; RNA-directed DNA polymerase; Shelterin Complex; siRNA; Squamous cell carcinoma; Statistical analysis; Statistics; Survival; Telomerase; Telomerase - genetics; Telomerase - metabolism; Telomerase reverse transcriptase; Telomere-binding protein; Telomere-Binding Proteins - genetics; Telomere-Binding Proteins - metabolism; Telomeres; Tripeptidyl-Peptidase 1; Tumor cell lines; Uterine Cervical Dysplasia - genetics; Uterine Cervical Dysplasia - metabolism; Uterine Cervical Dysplasia - mortality; Uterine Cervical Dysplasia - pathology; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - mortality; Uterine Cervical Neoplasms - pathology; Yeast; China; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0298118

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.