Telomere shortening in mucosa surrounding the tumor: Biosensor of field cancerization and prognostic marker of mucosal failure in head and neck squamous cell carcinoma
Telomere shortening in mucosa surrounding the tumor: Biosensor of field cancerization and prognostic marker of mucosal failure in head and neck squamous cell carcinoma
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DOI：
10.1016/j.oraloncology.2015.02.100
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发表时间：
2015-05-01
期刊：
影响因子：
4.8
通讯作者：
De Rossi, Anita
中科院分区：
文献类型：
--
作者：
Boscolo-Rizzo, Paolo;Rampazzo, Enrica;De Rossi, Anita
目的：本研究的目的是探讨端粒长度和端粒酶在癌组织和周围粘膜（SM）中的表达模式，作为头颈部鳞状细胞癌（HNSCC）成功治疗的患者野地癌变和临床结局的标志。材料和方法：本研究为前瞻性队列研究。采用实时荧光定量PCR技术对139例和90例HNSCC患者的癌组织和SM中端粒长度和端粒酶逆转录酶（TERT）转录物水平进行了定量分析。结果：SM患者端粒长度与年龄无相关性。端粒较短的SM患者发生粘膜衰竭的风险较高（调整后HR = 4.29）。肿瘤组织中TERT水平高的患者有较高的局部衰竭（HR = 2.88）、远处衰竭（HR = 7.27）、较差的疾病特异性生存（相关死亡HR = 2.62）的风险，但没有粘膜衰竭的风险。SM中端粒短、癌中TERT水平高的高危患者总体生存率显著降低（HR = 2.46）。结论：总的来说，这些发现表明，SM的端粒缩短是现场癌变的标志，可能先于TERT的再激活。SM中的短端粒是粘膜衰竭的强烈预后因素，而癌组织中的TERT水平随着疾病的侵袭性而增加，是肿瘤扩散的预后因素。(C) 2015 Elsevier Ltd.版权所有。
Objectives: The aim of the present study was to investigate the pattern of telomere length and telomerase expression in cancer tissues and the surrounding mucosa (SM), as markers of field cancerization and clinical outcome in patients successfully treated for with head and neck squamous cell carcinoma (HNSCC).Materials and methods: This investigation was a prospective cohort study. Telomere length and levels of telomerase reverse transcriptase (TERT) transcripts were quantified by real-time PCR in cancer tissues and SM from 139 and 90 patients with HNSCC, respectively.Results: No correlation was found between age and telomere length in SM. Patients with short telomeres in SM had a higher risk of mucosal failure (adjusted HR = 4.29). Patients with high TERT levels in cancer tissues had a higher risk of regional failure (HR = 2.88), distant failure (HR = 7.27), worse disease-specific survival (HR for related death = 2.62) but not mucosal failure. High-risk patients having both short telomeres in SM and high levels of TERT in cancer showed a significantly lower overall survival (HR = 2.46).Conclusions: Overall these findings suggest that telomere shortening in SM is a marker of field cancerization and may precede reactivation of TERT. Short telomeres in SM are strongly prognostic of mucosal failure, whereas TERT levels in cancer tissues increase with the aggressiveness of the disease and are prognostic of tumor spread. (C) 2015 Elsevier Ltd. All rights reserved.