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Higher expression of chemokine receptor CXCR7 is linked to early and metastatic recurrence in pathological stage I nonsmall cell lung cancer
Article first published online: 23 MAR 2009
Copyright © 2009 American Cancer Society
Volume 115, Issue 11, pages 2580–2593, 1 June 2009
How to Cite
Iwakiri, S., Mino, N., Takahashi, T., Sonobe, M., Nagai, S., Okubo, K., Wada, H., Date, H. and Miyahara, R. (2009), Higher expression of chemokine receptor CXCR7 is linked to early and metastatic recurrence in pathological stage I nonsmall cell lung cancer. Cancer, 115: 2580–2593. doi: 10.1002/cncr.24281
- Issue published online: 20 MAY 2009
- Article first published online: 23 MAR 2009
- Manuscript Accepted: 18 NOV 2008
- Manuscript Revised: 29 OCT 2008
- Manuscript Received: 29 MAY 2008
- chemokine receptor;
- postoperative metastatic recurrence;
- epidermal growth factor receptor;
- disease-free survival;
- real-time quantitative reverse transcriptase–polymerase chain reaction;
- nonsmall cell lung cancer
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).
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.
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).
Higher expression of CXCR7 is associated with Rec-Distant and poor DFS in patients with p-stage I NSCLC. Cancer 2009. © 2009 American Cancer Society.