TY - JOUR
T1 - Prognostic factors in resected stage I non-small-cell lung cancer
T2 - A multivariate analysis of six molecular markers
AU - Lu, Charles
AU - Soria, Jean Charles
AU - Tang, Ximing
AU - Xu, Xiao Chun
AU - Wang, Luo
AU - Mao, Li
AU - Lotan, Reuben
AU - Kemp, Bonnie
AU - Bekele, B. Nebiyou
AU - Feng, Lei
AU - Hong, Waun K.
AU - Khuri, Fadlo R.
PY - 2004
Y1 - 2004
N2 - Purpose: To analyze the prognostic significance of six molecular biomarkers (death-associated protein kinase [DAPK] promoter methylation, interleukin-10 [IL-10] protein expression, cyclooxygenase-2 [COX-2] mRNA expression, human telomerase reverse transcriptase catalytic subunit [hTERT] mRNA expression, retinoic acid receptor-beta [RAR-β] mRNA expression, and K-ras mutational status) in stage I non-small-cell lung cancer (NSCLC) patients. Patients and Methods: Biomarker analyses were performed on tumors from 94 patients with stage I NSCLC who underwent surgical resection at our institution. A minimum follow-up period of 5 years was required. DAPK methylation was assessed by methylation-specific polymerase chain reaction (PCR). RAR-β, COX-2, and hTERT mRNA levels were determined by in situ hybridization with digoxigenin-labeled antisense riboprobes. K-ras mutation status was determined by the PCR-primer introduced restriction with enrichment for mutant alleles method. IL-10 protein expression was analyzed by immunohistochemistry using a polyclonal antihuman IL-10 antibody. Cancer-specific survival was analyzed with a Cox proportional hazards model. To identify independent prognostic factors, a stepwise selection method was used. Results: DAPK methylation, IL-10 lack of expression, COX-2 expression, hTERT expression, RAR-β expression, and K-ras mutations were observed in 46.8%, 29.8%, 59.6%, 34.0%, 23.4%, and 34.0% of patients, respectively. In the final model, DAPK methylation and IL-10 lack of expression were significant negative prognostic factors for cancer-specific survival, whereas COX-2 expression was of borderline significance. Conclusion: In this cohort of resected stage I NSCLC patients, molecular markers that independently predict cancer-specific survival have been identified. The prognostic roles of DAPK methylation, IL-10, and other biomarkers in NSCLC merit further investigation.
AB - Purpose: To analyze the prognostic significance of six molecular biomarkers (death-associated protein kinase [DAPK] promoter methylation, interleukin-10 [IL-10] protein expression, cyclooxygenase-2 [COX-2] mRNA expression, human telomerase reverse transcriptase catalytic subunit [hTERT] mRNA expression, retinoic acid receptor-beta [RAR-β] mRNA expression, and K-ras mutational status) in stage I non-small-cell lung cancer (NSCLC) patients. Patients and Methods: Biomarker analyses were performed on tumors from 94 patients with stage I NSCLC who underwent surgical resection at our institution. A minimum follow-up period of 5 years was required. DAPK methylation was assessed by methylation-specific polymerase chain reaction (PCR). RAR-β, COX-2, and hTERT mRNA levels were determined by in situ hybridization with digoxigenin-labeled antisense riboprobes. K-ras mutation status was determined by the PCR-primer introduced restriction with enrichment for mutant alleles method. IL-10 protein expression was analyzed by immunohistochemistry using a polyclonal antihuman IL-10 antibody. Cancer-specific survival was analyzed with a Cox proportional hazards model. To identify independent prognostic factors, a stepwise selection method was used. Results: DAPK methylation, IL-10 lack of expression, COX-2 expression, hTERT expression, RAR-β expression, and K-ras mutations were observed in 46.8%, 29.8%, 59.6%, 34.0%, 23.4%, and 34.0% of patients, respectively. In the final model, DAPK methylation and IL-10 lack of expression were significant negative prognostic factors for cancer-specific survival, whereas COX-2 expression was of borderline significance. Conclusion: In this cohort of resected stage I NSCLC patients, molecular markers that independently predict cancer-specific survival have been identified. The prognostic roles of DAPK methylation, IL-10, and other biomarkers in NSCLC merit further investigation.
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U2 - 10.1200/JCO.2004.01.091
DO - 10.1200/JCO.2004.01.091
M3 - Article
C2 - 15542809
AN - SCOPUS:16544386625
SN - 0732-183X
VL - 22
SP - 4575
EP - 4583
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 22
ER -