Clinical significance of NQO1 polymorphism and expression of p53, SOD2, PARP1 in limited-stage small cell lung cancer

局限期小细胞肺癌NQO1基因多态性及p53、SOD2、PARP1表达的临床意义

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作者:Ho-Cheol Kim, Joon Seon Song, Jae Cheol Lee, Dae Ho Lee, Sang-We Kim, Jung-Shin Lee, Woo Sung Kim, Jin Kyung Rho, Sun Ye Kim, Chang-Min Choi

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).

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.

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.

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