Lower ataxia telangiectasia mutated (ATM) mRNA expression is correlated with poor outcome of laryngeal and pharyngeal cancer patients.
BACKGROUND
Ataxia telangiectasia mutated (ATM) kinase is a critical regulator in initiating DNA damage response and activating DNA repair. However, the correlation between ATM expression and the outcome of laryngopharyngeal cancer patients is unknown. We hypothesize that ATM expression is correlated with a worse outcome in laryngopharyngeal cancer patients.


METHODS
The ATM messenger RNA (mRNA) expression of 80 tumors of laryngeal and pharyngeal cancer was examined by real-time quantitative RT-PCR. Overall survival rates were measured using Kaplan-Meier estimates and the log-rank tests. The adjusted hazard rate ratios (HRRs) were computed by multivariate Cox regressions.


RESULTS
Reduced ATM mRNA was found in 65 of 80 studied cases. Lower ATM expression [tumor/normal <0.3, HRR = 2.49; 95% confidence interval (CI) 1.27-4.88], younger age (<55 years, HRR = 2.71; 95% CI 1.16-6.32), and larger tumor (T(3)/T(4), HRR = 2.21; 95% CI 1.10-4.44) were independent risk factors for survival. Patients with lower ATM and younger age (HRR = 6.51; 95% CI 2.05-20.66) or with lower ATM and T(3)/T(4) tumor (HRR = 5.23; 95% CI 2.04-13.40) exhibited the poorest outcome.


CONCLUSIONS
The expression of ATM mRNA, which is frequently downregulated in laryngeal and pharyngeal cancers, could be a valuable prognostic marker.
Department of Otolaryngology, Kaohsiung Medical University Hospital, Kaohsiung; Department of Otolaryngology, Faculty of Medicine, College of Medicine; Kaohsiung Medical University, Kaohsiung; Department of Otolaryngology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung.
K-W
KW
Lee
Graduate Institute of Medicine, College of Medicine, Kaohsiung; Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung.
Y-S
YS
Tsai
Department of Otolaryngology, Kaohsiung Medical University Hospital, Kaohsiung; Department of Otolaryngology, Faculty of Medicine, College of Medicine; Kaohsiung Medical University, Kaohsiung.
F-Y
FY
Chiang
Department of Bioscience Technology, Chang Jung Christian University, Tainan.
J-L
JL
Huang
Department of Otolaryngology, Kaohsiung Medical University Hospital, Kaohsiung; Department of Otolaryngology, Faculty of Medicine, College of Medicine; Kaohsiung Medical University, Kaohsiung.
K-Y
KY
Ho
Department of Dental Hygiene, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung.
Y-H
YH
Yang
Department of Otolaryngology, Kaohsiung Medical University Hospital, Kaohsiung; Department of Otolaryngology, Faculty of Medicine, College of Medicine; Kaohsiung Medical University, Kaohsiung.
W-R
WR
Kuo
Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua; School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
M-K
MK
Chen
Graduate Institute of Medicine, College of Medicine, Kaohsiung; Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung. Electronic address: csl@kmu.edu.tw.
C-S
CS
Lin
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007822:Laryngeal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010610:Pharyngeal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases