Browsing by Author "Lin, Chun-Hsuan"

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Expression Status of Ribonucleotide Reductase Small Subunits hRRM2/p53R2 as Prognostic Biomarkers in Stage I and II Non-small Cell Lung Cancer
(2011-10-01)
Hsu, Nan-Yung
;
Wu, Jeng-Yuan
;
Liu, Xiyong
;
Yen, Yun
;
Chen, Chih-Yi
Overexpression of ribonucleotide reductase M2 (hRRM2) and p53-dependent RR small subunit (p53R2) has been correlated with tumor malignancy and progression in several types of cancer. The aim of this study was to determine the association of p53R2/hRRM2 expression with clinicopathological characteristics of stage I and II non-small cell lung cancer (NSCLC). Immunohistochemistry was conducted on a tissue array that included 92 samples. Correlations between hRRM2 and p53R2 expression and clinicopathological factors, recurrence/metastasis, and outcomes were analyzed. The analyses revealed that there was no correlation between p53R2 expression and clinicopathological factors; hRRM2 was only positively related to poor tumor differentiation (p=0.006). Regarding overall survival during the follow-up period, patients with p53R2+/hRRM2- tumors had the best outcomes (p<0.01). Multivariant Cox analysis revealed that p53R2 (risk=0.232, 95% CI=0.086-0.626, p=0.004) not only served as a prognostic biomarker to predict survival, but also as an independent biomarker to predict disease-free survival (risk=0.545, 95% CI=0.301-0.987, p=0.045) of patients with NSCLC. Therefore, we consider that the expression of p53R2 can be used not only as a biomarker for overall survival, but also as an indicator for tumor recurrence. Based on our finding, p53R2 expression seems more important than that of hRRM2 in prognosis of early-stage lung cancer.
The APE1 Asp/Asp Genotype and the Combination of APE1 Asp/Asp and hOGG1-Cys Variants Are Associated With Increased p53 Mutation in Non-Small Cell Lung Cancer
(2012-11-01)
Lin, Chun-Hsuan
;
Chen, Po-Ming
;
Cheng, Ya-Wen
;
Chen, Chih-Yi
;
Yuan, Chiun-Jye
Background: The hOGG1 Ser326Cys polymorphism is associated with lung cancer risk, but there are limited data regarding an association between the APE1 Asp148Glu polymorphism and lung cancer. Biological evidence shows that the hOGG1-Cys allele results in less DNA repair activity; however, this is not associated with p53 mutation in lung cancer. Therefore, we investigated whether an interaction between 110001 and APE1 is associated with the frequency of p53 mutation in lung cancer. Methods: We studied 217 Taiwanese adults with primary lung cancer. DNA polymorphisms of hOGG1 and APE1 were determined by polymerase chain reaction (PCR)-based restriction fragment length polymorphism. Mutations in p53 exons 5-8 were detected by direct sequencing. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% CIs for the risk of p53 mutation associated with polymorphisms of hOGG1 and APE I in lung cancer. Results: As expected, no association between hOGG1 polymorphism and p53 mutation was observed in this population. However, a higher risk of p53 mutation was found in participants with the APE I Asp/Asp genotype than in those with the APE1-Glu allele (OR, 2.15; 95% CI, 1.19-3.87; P = 0.011). The risk of p53 mutation was also higher in participants with APEI Asp/Asp plus hOGG1-Cys than in those with APE1-Glu plus hOGG1 Ser/Ser (OR, 3.72; 95% Cl, 1.33-10.40; P = 0.012). Conclusions: These results suggest that the APE I Asp/Asp genotype and the combination of the APE I Asp/Asp and hOGG1-Cys variants are associated with increased risk of p53 mutation in non small cell lung cancer.