Predictive and prognostic significance of telomerase levels/telomere length in tissues and peripheral blood in head and neck squamous cell carcinoma

被引:10
作者
Boscolo-Rizzo, Paolo [1 ,2 ]
Rampazzo, Enrica [3 ]
Polesel, Jerry [4 ]
Giunco, Silvia [3 ]
Menegaldo, Anna [1 ,2 ]
Mantovani, Monica [1 ,2 ]
Stellin, Marco [1 ,2 ]
Bandolin, Luigia [1 ,2 ]
Spinato, Giacomo [1 ,2 ,3 ]
Del Mistro, Annarosa [5 ]
Borsetto, Daniele [6 ]
Fussey, Jonathan [7 ]
Tirelli, Giancarlo [8 ]
Da Mosto, Maria Cristina [1 ,2 ]
De Rossi, Anita [3 ,5 ]
机构
[1] Univ Padua, Sect Otolaryngol, Dept Neurosci, Treviso, Italy
[2] Univ Padua, Reg Ctr Head & Neck Canc, Treviso, Italy
[3] Univ Padua, Dept Surg Oncol & Gastroenterol, Sect Oncol & Immunol, Padua, Italy
[4] IRCCS, Ctr Riferimento Oncol Aviano CRO, Unit Canc Epidemiol, Aviano, Italy
[5] IRCCS, Ist Oncol Veneto IOV, Immunol & Mol Oncol Unit, Padua, Italy
[6] Cambridge Univ Hosp, Addenbrookes Hosp, Dept ENT, Cambridge, England
[7] Royal Devon & Exeter Hosp, Dept Otolaryngol, Exeter, Devon, England
[8] Univ Trieste, Hosp Cattinara, Head & Neck Dept, Trieste, Italy
关键词
FIELD CANCERIZATION; HUMAN-PAPILLOMAVIRUS; IONIZING-RADIATION; MESSENGER-RNA; CANCER; PLASMA; TUMOR; EXPRESSION; RESISTANCE; SENESCENCE;
D O I
10.1038/s41598-019-54028-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A growing body of evidence indicates that the expression of TERT, the catalytic subunit of telomerase, is a biological marker of progression in several cancers. We investigated the predictive and prognostic role of TERT levels and telomere length in tissues and peripheral blood in patients with head and neck squamous cell carcinoma (HNSCC). High TERT levels in cancer tissues were independently associated with worse response to therapy (odds ratio [OR]:6.26), regional failure (hazard ratio [HR]:5.75), progression (HR:2.12), and death (HR:3.53). Longer telomeres in the mucosa surrounding the tumor (SM) were independently associated with a lower risk of mucosal failure (HR:0.39). While telomere length in peripheral blood mononuclear cells (PBMC) significantly decreased with age, no correlation was found between age and telomere length in SM. No associations were found between TERT levels in plasma and telomere length in PBMC and the prognostic variables. High levels of TERT transcripts in cancer cells represent a reliable prognostic marker for identifying HNSCC patients with risk of progression. The altered relationship of telomere length to age in SM compared with PBMC suggests that in a subset of cases the phenotypically normal SM constitutes an acquired telomere-shortened epithelial field prone to genetic instability.
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收藏
页数:11
相关论文
共 44 条
  • [1] Telomere lengths in the oral epithelia with and without carcinoma
    Aida, Junko
    Izumo, Toshiyuki
    Shimomura, Naotaka
    Nakamura, Ken-ichi
    Ishikawa, Naoshi
    Matsuura, Masaaki
    Poon, Steven S.
    Fujiwara, Mutsunori
    Sawabe, Motoji
    Arai, Tomio
    Takubo, Kaiyo
    [J]. EUROPEAN JOURNAL OF CANCER, 2010, 46 (02) : 430 - 438
  • [2] Reactivation of telomerase in cancer
    Akincilar, Semih Can
    Unal, Bilal
    Tergaonkar, Vinay
    [J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2016, 73 (08) : 1659 - 1670
  • [3] Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer
    Ang, K. Kian
    Harris, Jonathan
    Wheeler, Richard
    Weber, Randal
    Rosenthal, David I.
    Nguyen-Tan, Phuc Felix
    Westra, William H.
    Chung, Christine H.
    Jordan, Richard C.
    Lu, Charles
    Kim, Harold
    Axelrod, Rita
    Silverman, C. Craig
    Redmond, Kevin P.
    Gillison, Maura L.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (01) : 24 - 35
  • [4] Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice
    Artandi, SE
    Chang, S
    Lee, SL
    Alson, S
    Gottlieb, GJ
    Chin, L
    DePinho, RA
    [J]. NATURE, 2000, 406 (6796) : 641 - 645
  • [5] Epigenetic field cancerization in gastrointestinal cancers
    Baba, Yoshifumi
    Ishimoto, Takatsugu
    Kurashige, Junji
    Iwatsuki, Masaaki
    Sakamoto, Yasuo
    Yoshida, Naoya
    Watanabe, Masayuki
    Baba, Hideo
    [J]. CANCER LETTERS, 2016, 375 (02) : 360 - 366
  • [6] Boscolo-Rizzo P, 2013, ACTA OTORHINOLARYNGO, V33, P77
  • [7] Telomeres and telomerase in head and neck squamous cell carcinoma: from pathogenesis to clinical implications
    Boscolo-Rizzo, Paolo
    Da Mosto, Maria Cristina
    Rampazzo, Enrica
    Giunco, Silvia
    Del Mistro, Annarosa
    Menegaldo, Anna
    Baboci, Lorena
    Mantovani, Monica
    Tirelli, Giancarlo
    De Rossi, Anita
    [J]. CANCER AND METASTASIS REVIEWS, 2016, 35 (03) : 457 - 474
  • [8] Telomere shortening in mucosa surrounding the tumor: Biosensor of field cancerization and prognostic marker of mucosal failure in head and neck squamous cell carcinoma
    Boscolo-Rizzo, Paolo
    Rampazzo, Enrica
    Perissinotto, Egle
    Piano, Maria Assunta
    Giunco, Silvia
    Baboci, Lorena
    Spinato, Giacomo
    Spinato, Roberto
    Tirelli, Giancarlo
    Da Mosto, Maria Cristina
    Del Mistro, Annarosa
    De Rossi, Anita
    [J]. ORAL ONCOLOGY, 2015, 51 (05) : 500 - 507
  • [9] Braakhuis BJM, 2003, CANCER RES, V63, P1727
  • [10] Califano J, 1999, CLIN CANCER RES, V5, P1862