Expression status of folate receptor α is significantly correlated with prognosis in non-small-cell lung cancers

被引:103
作者
Iwakiri, Shotaro [1 ]
Sonobe, Makoto [1 ]
Nagai, Shinjiro [1 ]
Hirata, Toshiki [1 ]
Wada, Hiromi [1 ]
Miyahara, Ryo [1 ]
机构
[1] Kyoto Univ, Fac Med, Dept Thorac Surg, Sakyo Ku, Kyoto 6068507, Japan
关键词
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);
D O I
10.1245/s10434-007-9755-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:889 / 899
页数:11
相关论文
共 50 条
[1]   POTOCYTOSIS - SEQUESTRATION AND TRANSPORT OF SMALL MOLECULES BY CAVEOLAE [J].
ANDERSON, RGW ;
KAMEN, BA ;
ROTHBERG, KG ;
LACEY, SW .
SCIENCE, 1992, 255 (5043) :410-411
[2]   Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses [J].
Bhattacharjee, A ;
Richards, WG ;
Staunton, J ;
Li, C ;
Monti, S ;
Vasa, P ;
Ladd, C ;
Beheshti, J ;
Bueno, R ;
Gillette, M ;
Loda, M ;
Weber, G ;
Mark, EJ ;
Lander, ES ;
Wong, W ;
Johnson, BE ;
Golub, TR ;
Sugarbaker, DJ ;
Meyerson, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :13790-13795
[3]   INCREASED EXPRESSION AND CHARACTERIZATION OF 2 DISTINCT FOLATE BINDING-PROTEINS IN MURINE ERYTHROLEUKEMIA-CELLS [J].
BRIGLE, KE ;
SPINELLA, MJ ;
WESTIN, EH ;
GOLDMAN, ID .
BIOCHEMICAL PHARMACOLOGY, 1994, 47 (02) :337-345
[4]   The α folate receptor is highly activated in malignant pleural mesothelioma [J].
Bueno, R ;
Appasani, K ;
Mercer, H ;
Lester, S ;
Sugarbaker, D .
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 2001, 121 (02) :225-233
[5]  
CAMPBELL IG, 1991, CANCER RES, V51, P5329
[6]  
Chiao JH, 1997, J BIOL CHEM, V272, P11165, DOI 10.1074/jbc.272.17.11165
[7]   Folate and carcinogenesis: An integrated scheme [J].
Choi, SW ;
Mason, JB .
JOURNAL OF NUTRITION, 2000, 130 (02) :129-132
[8]   FDA drug approval summary:: Pemetrexed for injection (Alimta®) for the treatment of non-small cell lung cancer [J].
Cohen, MH ;
Johnson, JR ;
Wang, YC ;
Sridhara, R ;
Pazdur, R .
ONCOLOGIST, 2005, 10 (06) :363-368
[9]  
FRANKLIN WA, 1994, INT J CANCER S, V8, P20
[10]   Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer [J].
Fukuoka, M ;
Yano, S ;
Giaccone, G ;
Tamura, T ;
Nakagawa, K ;
Douillard, JY ;
Nishiwaki, Y ;
Vansteenkiste, J ;
Kudoh, S ;
Rischin, D ;
Eek, R ;
Horai, T ;
Noda, K ;
Takata, I ;
Smit, E ;
Averbuch, S ;
Macleod, A ;
Feyereislova, A ;
Dong, RP ;
Baselga, J .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (12) :2237-2246