Clinical significance of NQO1 polymorphism and expression of p53, SOD2, PARP1 in limited-stage small cell lung cancer.
BACKGROUND
Small cell lung cancer (SCLC) is one of highly aggressive cancers with poor prognosis. Unfortunately, there are as yet no molecular targets that can be exploited to prolong survival in patients with SCLC. This study aimed to investigate possible molecular markers associated with prognosis in limited-stage small cell lung cancer (LS-SCLC).


METHODS
The demographic and clinical data for LS-SCLC patients treated in a tertiary care hospital between January 2008 and December 2012 were retrospectively reviewed. NQO1 polymorphism and the expression of p53, SOD2, PARP1 were examined in biopsy specimens, and the factors affecting prognosis were identified.


RESULTS
79 patients with LS-SCLC having available pathologic tissues were analyzed. 84.8% of them received both chemotherapy and radiotherapy. NQO1 polymorphism was detected in 60.0% (45/79; heterozygous in 26 patients, homozygous in 19 patients). Over-expression of p53, SOD2, PARP1 was seen in 45.6% (36/79), 38.0% (30/79) and 41.8% (33/79) of the patients, respectively. The univariate Cox proportional hazards model revealed that serum lactate dehydrogenase (LDH) levels and PARP1 expression were associated with disease progression. In the multivariate analysis, only PARP1 expression was a significant independent prognostic factor for progression-free survival (hazard ratio: 0.494; 95% CI, 0.267-0.913, P = 0.025).


CONCLUSIONS
PARP1 expression is correlated with longer progression-free survival in LS-SCLC requiring further studies to clarify the precise role of PARP1 and the relevance of PARP1-targeted therapy.
Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine Seoul, South Korea.
Ho-Cheol
HC
Kim
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine Seoul, South Korea.
Joon Seon
JS
Song
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine Seoul, South Korea.
Jae Cheol
JC
Lee
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine Seoul, South Korea.
Dae Ho
DH
Lee
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine Seoul, South Korea.
Sang-We
SW
Kim
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine Seoul, South Korea.
Jung-Shin
JS
Lee
Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine Seoul, South Korea.
Woo Sung
WS
Kim
Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine Seoul, South Korea ; Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine Seoul, South Korea.
Jin Kyung
JK
Rho
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine Seoul, South Korea.
Sun Ye
SY
Kim
Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine Seoul, South Korea ; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine Seoul, South Korea.
Chang-Min
CM
Choi
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood / Q000235:genetics; D001706:Biopsy; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D009367:Neoplasm Staging; D010641:Phenotype; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000097:blood / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013482:Superoxide Dismutase / Q000032:analysis*; D062606:Tertiary Care Centers; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D000099156:Superoxide Dismutase 2
D014408:Biomarkers, Tumor; D007770:L-Lactate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D013482:Superoxide Dismutase; D016159:Tumor Suppressor Protein p53; D000099156:Superoxide Dismutase 2; C495901:TP53 protein, human; C447479:NQO1 protein, human; C499320:PARP1 protein, human
NQO1 polymorphism; PARP1; Small cell lung cancer; prognosis