Higher expression of chemokine receptor CXCR7 is linked to early and metastatic recurrence in pathological stage I nonsmall cell lung cancer.
BACKGROUND
The authors elucidated particular chemokine receptors that are expressed on lung cancer cells, as well as the clinical significance of the expression of these chemokine receptors in completely resected nonsmall cell lung cancer (NSCLC).


METHODS
The authors examined gene expression of chemokine receptors (CCR1-11, CXCR1-7, XCR1, and CX3CR1) in 11 cell lines of lung cancer, and gene expression of CXCR3, CXCR4, and CXCR7 (CXCR3/4/7) in surgical specimens of 127 patients who underwent complete resection for their NSCLC between May 2001 and December 2002, using quantitative real-time reverse transcriptase-polymerase chain reaction (PCR). Mutation detection analysis of the EGFR genes using the PCR single-strand conformational polymorphism method was evaluated in patients with pathological (p-) stage I adenocarcinoma.


RESULTS
Substantial expression of CXCR3/4/7 mRNA was observed in all NSCLC cell lines examined. In p-stage I NSCLC, CXCR4 and CXCR7 expression values in patients with postoperative metastatic recurrence (Rec-Distant) were significantly higher than in those without recurrences (P = .003 and P = .007, respectively). In addition, the 5-year disease-free survival (DFS) rate of high CXCR7-expressing patients (63.2%) was significantly lower than that of low CXCR7-expressing patients (84.8%) (P = .033). The EGFR mutation was significantly more frequent in patients with higher CXCR7 expression (14 of 21 patients) than in those with lower CXCR7 expression (12 of 32 patients) (P = .038). A multivariate analysis confirmed that high CXCR7 expression was an independent and significant factor predicting a poor DFS in p-stage I NSCLC patients (P = .041).


CONCLUSIONS
Higher expression of CXCR7 is associated with Rec-Distant and poor DFS in patients with p-stage I NSCLC.
Iwakiri
Shotaro
S
Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
Mino
Nobuya
N
Takahashi
Tsuyoshi
T
Sonobe
Makoto
M
Nagai
Shinjiro
S
Okubo
Kenichi
K
Wada
Hiromi
H
Date
Hiroshi
H
Miyahara
Ryo
R
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D054387:Receptors, CXCR / Q000235:genetics* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics
C501896:ACKR3 protein, human; D014408:Biomarkers, Tumor; D054387:Receptors, CXCR; D019718:Receptors, CXCR4