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10.1245/s10434-007-9755-3
Annals of Surgical Oncology 15:889-899 (2008)
© 2008 Society of Surgical Oncology
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Original Article

Expression Status of Folate Receptor {alpha} Is Significantly Correlated with Prognosis in Non-Small-Cell Lung Cancers

Shotaro Iwakiri, MD , Makoto Sonobe, MD, PhD , Shinjiro Nagai, MD , Toshiki Hirata, MD, PhD , Hiromi Wada, MD, PhD and Ryo Miyahara, MD, PhD

Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Shogoin-Kawara-cho 54, Sakyo-ku, Kyoto, 606-8507, Japan

Correspondence: Address correspondence and reprint requests to: Ryo Miyahara, MD, PhD; E-mail: . rmiyahar{at}kuhp.kyoto-u.ac.jp

Background: To evaluate the prognostic value of folate receptor {alpha} (FOLR1) and/or reduced folate carrier (RFC1) expression, which are well-characterized folate transporters, in completely resected non-small-cell lung cancer (NSCLC).

Methods: We quantitatively examined gene expression of FOLR1 and RFC1 in surgical specimens resected from NSCLC patients. A total of 119 consecutive patients from January 2003 to June 2004 were included.

Results: In adenocarcinoma, the FOLR1 gene expression was downregulated in smokers and male patients (P = 0.006 and P < 0.001, respectively). In addition, FOLR1 expression values in patients with well-differentiated, early p-stage, pT1, pN0, EGFR mutant, and p53 wild-type cancers were significantly higher than those for poorly differentiated, advanced p-stage, pT2-4, pN1-3, EGFR wild-type, and p53 mutant (P < 0.001, P < 0.001, P < 0.001, P = 0.002, P < 0.001 and P = 0.023, respectively). In squamous cell carcinoma, FOLR1 expression values in patients with pN1-3 was significantly higher than those with pN0 (P = 0.037). Moreover, the 3-year survival rate and disease-free survival rate of high-FOLR1-expressing patients (94.7% and 75.4%) were significantly higher than those of low-FOLR1-expressing patients (80.9% and 60.8%) (P = 0.008 and P = 0.038). A multivariate analysis confirmed that high FOLR1 expression was an independent and significant factor predicting a favorable prognosis (P = 0.043).

Conclusions: Higher levels of FOLR1 appear to be associated with better prognoses for patients with lung adenocarcinomas.

Key Words: Folate receptor {alpha}(FOLR1) • Reduced folate carrier (RFC1) • Epidermal growth factor receptor (EGFR) • Prognosis • Real-time quantitative RT-PCR • Non-small-cell lung cancer (NSCLC)






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