title: Expression status of ribonucleotide reductase small subunits hRRM2/p53R2 as prognostic biomarkers in stage I and II non-small cell lung cancer.
abstract: 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.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, No. 110. Sec. 1, Jianguo N. Rd., Taichung 4020, Taiwan, R.O.C.
authors.forename: Nan-Yung
authors.initials: NY
authors.lastname: Hsu
authors.forename: Jeng-Yuan
authors.initials: JY
authors.lastname: Wu
authors.forename: Xiyong
authors.initials: X
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Chou
authors.forename: Chun-Hsuan
authors.initials: CH
authors.lastname: Lin
authors.forename: Huei
authors.initials: H
authors.lastname: Lee
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D021122:Protein Subunits / Q000378:metabolism*; D012262:Ribonucleoside Diphosphate Reductase / Q000378:metabolism*; D012264:Ribonucleotide Reductases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D021122:Protein Subunits; C405947:RRM2B protein, human; D012264:Ribonucleotide Reductases; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase