DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer.
BACKGROUND
RRM1, the regulatory subunit of ribonucleotide reductase, is involved in carcinogenesis, tumor progression, and the response of non-small-cell lung cancer to treatment.


METHODS
We developed an automated quantitative determination of the RRM1 protein in routinely processed histologic specimens. In these specimens, we measured the expression of RRM1 and two other proteins that are relevant to non-small-cell lung cancer: the excision repair cross-complementation group 1 (ERCC1) protein and the phosphatase and tensin homologue (PTEN). We compared the results with the clinical outcomes in 187 patients with early-stage non-small-cell lung cancer who had received only surgical treatment.


RESULTS
RRM1 expression correlated with the expression of ERCC1 (P<0.001) but not with the expression of PTEN (P=0.37). The median disease-free survival exceeded 120 months in the group of patients with tumors that had high expression of RRM1 and was 54.5 months in the group with low expression of RRM1 (hazard ratio for disease progression or death in the high-expression group, 0.46; P=0.004). The overall survival was more than 120 months for patients with tumors with high expression of RRM1 and 60.2 months for those with low expression of RRM1 (hazard ratio for death, 0.61; P=0.02). Among these 187 patients, the survival advantage was limited to the 30% of patients with tumors that had a high expression of both RRM1 and ERCC1.


CONCLUSIONS
RRM1 and ERCC1 are determinants of survival after surgical treatment of early-stage, non-small-cell lung cancer.
Zheng
Zhong
Z
From the Division of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
Chen
Tingan
T
Li
Xueli
X
Haura
Eric
E
Sharma
Anupama
A
Bepler
Gerold
G
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011379:Prognosis; D040081:Protein Array Analysis; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012262:Ribonucleoside Diphosphate Reductase; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D012313:RNA; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C071447:ERCC1 protein, human; D004720:Endonucleases; D051059:PTEN Phosphohydrolase