BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer.
Lung cancer is the most common cancer, with dismal outcome. Treatment approaches, including cisplatin-based chemotherapy and surgery, are currently based on the clinical classification of the tumor, without genetic assessment for predicting differential chemosensitivity. BRCA1 plays a central role in DNA repair, and decreased BRCA1 mRNA expression in the human breast cancer HCC1937 cell line caused cisplatin hypersensitivity, but the relation between BRCA1 and survival in lung cancer patients has never been examined. We used real-time quantitative polymerase chain reaction to determine BRCA1 mRNA levels in 55 surgically resected tumors of non-small-cell lung cancer patients who had received neoadjuvant gemcitabine/cisplatin chemotherapy, and divided the gene expression values into quartiles. When results were correlated with outcome, two cut-offs were observed; patients with levels <0.61 had better outcome, and those >2.45 had poorer outcome. Median survival was not reached for the 15 patients in the bottom quartile, whereas for the 28 in the two middle quartiles, it was 37.8 months (95% CI, 10.6-65), and for the 12 patients in the top quartile, it was 12.7 months (95% CI, 0.28-28.8) (P=0.01). Moreover, when patients were stratified by pathologic stage, those in the bottom quartile had a decreased risk of death (HR=0.206; 95% CI, 0.05-0.83; P=0.026) compared with those in the top quartile, and those in the two middle quartiles also had a decreased risk of death (HR=0.294; 95% CI, 0.10-0.83; P=0.020) compared with those in the top quartile. BRCA1 expression is potentially an important tool for use in cancer management and should be assessed for predicting differential chemosensitivity and tailoring chemotherapy in lung cancer.
Taron
Miquel
M
Medical Oncology Service, Institut Catala d'Oncologia, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
Rosell
Rafael
R
Felip
Enriqueta
E
Mendez
Pedro
P
Souglakos
John
J
Ronco
Maria Sanchez
MS
Queralt
Cristina
C
Majo
Joaquim
J
Sanchez
Jose Miguel
JM
Sanchez
Jose Javier
JJ
Maestre
Jose
J
D000368:Aged; D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D000093542:Gemcitabine
D019313:BRCA1 Protein; D012333:RNA, Messenger; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine