Upregulated human telomerase reverse transcriptase (hTERT) expression is associated with spinal chordoma growth, invasion and poor prognosis

被引:1
作者
Zou, Ming-Xiang [1 ]
Lv, Guo-Hua [1 ]
Li, Jing [1 ]
She, Xiao-Ling [2 ]
Jiang, Yi [2 ]
机构
[1] Cent South Univ, Xiangya Hosp 2, Dept Spine Surg, 139 Middle Renmin Rd, Changsha 410011, Hunan, Peoples R China
[2] Cent South Univ, Xiangya Hosp 2, Dept Pathol, Changsha 410011, Hunan, Peoples R China
来源
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH | 2016年 / 8卷 / 02期
关键词
Chordoma; human telomerase reverse transcriptase (hTERT); biomarker; prognosis; TUMOR-INFILTRATING LYMPHOCYTES; TERT PROMOTER MUTATIONS; LIGAND; PD-L1; OPERATIVE MANAGEMENT; LOW-AFFINITY; SURVIVAL; CANCER; PEPTIDE; CELLS; RNA;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Altered expression or activity of human telomerase reverse transcriptase (hTERT) has been associated with human carcinogenesis. This study detected hTERT expression in spinal chordoma tissues and associated the level of hTERT expression with clinicopathological data and patient survival. Tissue samples from 54 patients and 20 controls were subjected to immunohistochemical analysis of hTERT protein levels. hTERT expression levels were then analyzed for associations with patient survival rates and clinicopathological parameters (such as age, gender, tumor size, location, tumor grade, tumor stage, muscle invasion, recurrence or not, type of resection, tumor hemorrhage, tumor necrosis, levels of tumor-infiltrating lymphocytes (TILs) and Ki-67 expression). hTERT expression was detected in all 54 spinal chordomas. Expression levels were weak in 7, moderate in 17 and strong in 30 spinal chordoma tissue samples. In contrast, hTERT was rarely expressed in nucleus pulposus tissues (20 samples). hTERT expression was significantly associated with the Ki-67-staining index (t = -6.616, p < 0.001), TIL levels (F = 5.27, p = 0.008) and tumor invasion of the surrounding muscle tissue (t = -4.49, p < 0.001). Kaplan-Meier curves indicated that high hTERT expression was significantly associated with poor local recurrence-free survival of patients (chi(2) = 19.07, p < 0.001 via the log-rank test), but not associated with overall patient survival. Multivariate analysis of local recurrence-free survival demonstrated that hTERT expression was an independent prognostic factor among spinal chordoma patients (HR = 1.013, 95% CI: 1.002-1.024, p = 0.016). High hTERT expression was associated with spinal chordoma growth, invasion and poor patient prognosis. Future studies will investigate the use of hTERT as a biomarker to predict patient prognosis and disease progression or as a potential spinal chordoma therapy target.
引用
收藏
页码:516 / 529
页数:14
相关论文
共 61 条
  • [1] Prognostic significance of immunohistochemical expression of VEGFR2 and iNOS in spinal chordoma
    Akhavan-Sigari, Reza
    Gaab, Michael Robert
    Rohde, Veit
    Abili, Mehdi
    Ostertag, Helmut
    [J]. EUROPEAN SPINE JOURNAL, 2014, 23 (11) : 2416 - 2422
  • [2] Akhavan-Sigari R, 2014, ANTICANCER RES, V34, P623
  • [3] Prognostic Factors in Surgical Resection of Sacral Chordoma
    Angelini, Andrea
    Pala, Elisa
    Calabro, Teresa
    Maraldi, Marco
    Ruggieri, Pietro
    [J]. JOURNAL OF SURGICAL ONCOLOGY, 2015, 112 (04) : 344 - 351
  • [4] ARIEL I M, 1975, Journal of Surgical Oncology, V7, P27, DOI 10.1002/jso.2930070106
  • [5] Genes and pathways downstream of telomerase in melanoma metastasis
    Bagheri, Sepideh
    Nosrati, Mehdi
    Li, Shang
    Fong, Sylvia
    Torabian, Sima
    Rangel, Javier
    Moore, Dan H.
    Federman, Scot
    LaPosa, Rebecca R.
    Baehner, Frederick L.
    Sagebiel, Richard W.
    Cleaver, James E.
    Haqq, Christopher
    Debs, Robert J.
    Blackburn, Elizabeth H.
    Kashani-Sabet, Mohammed
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (30) : 11306 - 11311
  • [6] Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma
    Berghoff, Anna Sophie
    Kiesel, Barbara
    Widhalm, Georg
    Rajky, Orsolya
    Ricken, Gerda
    Woehrer, Adelheid
    Dieckmann, Karin
    Filipits, Martin
    Brandstetter, Anita
    Weller, Michael
    Kurscheid, Sebastian
    Hegi, Monika E.
    Zielinski, Christoph C.
    Marosi, Christine
    Hainfellner, Johannes A.
    Preusser, Matthias
    Wick, Wolfgang
    [J]. NEURO-ONCOLOGY, 2015, 17 (08) : 1064 - 1075
  • [7] Tumour-infiltrating lymphocytes and expression of programmed death ligand 1 (PD-L1) in melanoma brain metastases
    Berghoff, Anna Sophie
    Ricken, Gerda
    Widhalm, Georg
    Rajky, Orsolya
    Dieckmann, Karin
    Birner, Peter
    Bartsch, Rupert
    Hoeller, Christoph
    Preusser, Matthias
    [J]. HISTOPATHOLOGY, 2015, 66 (02) : 289 - 299
  • [8] Telomerase is an independent prognostic marker of overall survival in patients with colorectal cancer
    Bertorelle, R.
    Briarava, M.
    Rampazzo, E.
    Biasini, L.
    Agostini, M.
    Maretto, I.
    Lonardi, S.
    Friso, M. L.
    Mescoli, C.
    Zagonel, V.
    Nitti, D.
    De Rossi, A.
    Pucciarelli, S.
    [J]. BRITISH JOURNAL OF CANCER, 2013, 108 (02) : 278 - 284
  • [9] Vaccination of patients with advanced non-small-cell lung cancer with an optimized cryptic human telomerase reverse transcriptase peptide
    Bolonaki, Irini
    Kotsakis, Athanassios
    Papadimitraki, Elsa
    Aggouraki, Despoina
    Konsolakis, George
    Vagia, Aphrodite
    Christophylakis, Charalambos
    Nikoloudi, Irini
    Magganas, Elefterios
    Galanis, Athanassios
    Cordopatis, Paul
    Kosmatopoulos, Kostas
    Georgoulias, Vassilis
    Mavroudis, Dimitris
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (19) : 2727 - 2734
  • [10] Sorafenib in patients with locally advanced and metastatic chordomas: a phase II trial of the French Sarcoma Group (GSF/GETO)
    Bompas, E.
    Le Cesne, A.
    Tresch-Bruneel, E.
    Lebellec, L.
    Laurence, V.
    Collard, O.
    Saada-Bouzid, E.
    Isambert, N.
    Blay, J. Y.
    Amela, E. Y.
    Salas, S.
    Chevreau, C.
    Bertucci, F.
    Italiano, A.
    Clisant, S.
    Penel, N.
    [J]. ANNALS OF ONCOLOGY, 2015, 26 (10) : 2168 - 2173