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 (CCP1-11, CXCP1-7, XCP7, and CX3CP7) in 11 cell lines of lung cancer, and gene expression of CXCP3, CXCP4, and CXCP7 (CXCP3/4/7) 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 EGFP genes using the PCR single-strand conformational polymorphism method was evaluated in patients with pathological (p-) stage I adenocarcinoma. RESULTS: Substantial expression of CXCP3/4/7 mRNA was observed in all NSCLC cell lines examined. In p-stage I NSCLC, CXCP4 and CXCP7 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 CXCP7-expressing patients (63.2%) was significantly lower than that of low CXCP7-expressing patients (84.8%) (P=.033). The EGFP mutation was significantly more frequent in patients with higher CXCP7 expression (14 of 21 patients) than in those with lower CXCP7 expression (12 of 32 patients) (P=.038). A multivariate analysis confirmed that high CXCP7 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. Cancer 2009;115:2580-93.(C) 2009 American Cancer Society.