Browsing by Author "Chen, Chih-Yi"

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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
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Wu, Jeng-Yuan
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Liu, Xiyong
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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.
Landscape of Mitochondria Genome and Clinical Outcomes in Stage 1 Lung Adenocarcinoma
(2020-03-01)
Raghav, Lovely
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Chang, Ya-Hsuan
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Hsu, Yi-Chiung
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Li, Yu-Cheng
;
Chen, Chih-Yi
Risk factors including genetic effects are still being investigated in lung adenocarcinoma (LUAD). Mitochondria play an important role in controlling imperative cellular parameters, and anomalies in mitochondrial function might be crucial for cancer development. The mitochondrial genomic aberrations found in lung adenocarcinoma and their associations with cancer development and progression are not yet clearly characterized. Here, we identified a spectrum of mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with prognosis and clinical outcomes. Next-generation sequencing was used to reveal the mitochondrial genomes of tumor and conditionally normal adjacent tissues from 61 Stage 1 LUADs. Mitochondrial somatic mutations and clinical outcomes including relapse-free survival (RFS) were analyzed. Patients with somatic mutations in the D-loop region had longer RFS (adjusted hazard ratio, adjHR = 0.18, p = 0.027), whereas somatic mutations in mitochondrial Complex IV and Complex V genes were associated with shorter RFS (adjHR = 3.69, p = 0.012, and adjHR = 6.63, p = 0.002, respectively). The risk scores derived from mitochondrial somatic mutations were predictive of RFS (adjHR = 9.10, 95%CI: 2.93-28.32, p < 0.001). Our findings demonstrated the vulnerability of the mitochondrial genome to mutations and the potential prediction ability of somatic mutations. This research may contribute to improving molecular guidance for patient treatment in precision medicine.
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
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Chen, Po-Ming
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Cheng, Ya-Wen
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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.