RESEARCH ARTICLE Expression of the chemokine receptor CCR6 correlates with a favorable prognosis in patients with adenocarcinoma of the lung Yoshihiro Minamiya & Hajime Saito & Naoko Takahashi & Manabu Ito & Hiroshi Toda & Takashi Ono & Hayato Konno & Satoru Motoyama & Jun-ichi Ogawa Received: 27 July 2010 / Accepted: 13 September 2010 / Published online: 25 September 2010 # International Society of Oncology and BioMarkers (ISOBM) 2010 Abstract The relation between CCR6 expression and the clinicopathological characteristics of lung cancer and patient prognosis is not well understood and remains controversial. We, therefore, investigated the relationship between CCR6 expression and prognosis in patients with adenocarcinoma of the lung. We used semiquantitative real- time reverse transcription polymerase chain reaction to assess the expression of CCR6 mRNA in tumor samples from 84 patients with adenocarcinoma of the lung. We then correlated the levels of CCR6 mRNA with known clinico- pathological features. The 5-year disease-free survival rate among patients expressing higher levels of CCR6 mRNA was significantly better than among those expressing lower levels (P =0.009 by log-rank test). Multivariate Cox proportional hazard analyses revealed, being male [hazard ratio, 3.94; 95% confidence interval (CI), 1.58 to 10.36; P= 0.003], tumor size >30 mm (hazard ratio, 2.46; 95% CI, 1.08 to 5.73; P=0.030), nodal metastasis (hazard ratio, 7.66; 95% CI, 2.62 to 23.3; P=0.0002), and CCR6 (hazard ratio, 0.34; 95% CI, 0.11 to 0.93; P =0.034) to be independent factors affecting the 5-year disease-free sur- vival rate. Greater expression of CCR6 by tumor cells is an independent predictor of a better prognosis in patients with adenocarcinoma of the lung. Keywords Chemokine receptor . Lung cancer . Prognosis . Adenocarcinoma Introduction Non-small cell lung carcinoma (NSCLC) accounts for approximately 80% of all lung cancers, with adenocarcino- ma being the major histological subtype. Despite consider- able therapeutic progress, the prognosis of adenocarcinoma patients remains poor. This is in part because there is still a critical need for prognostic markers that would improve clinical treatment. For example, although TNM staging has proven to be a useful independent prognostic indicator for lung adenocarcinoma, it is believed that a better under- standing of the molecular biology could result in more efficient management of the disease. Chemokines are a family of low molecular weight (8– 10 kDa) proinflammatory cytokines that bind to G-protein- coupled receptors. They are grouped into four families, CXC, CC, C, and CX3C, on the basis of the positions of conserved cysteine residues [1]. Chemokines and their receptors play important roles in inflammation, infection, tissue injury, allergy, and cardiovascular disease, as well as in malignant tumors [2]. CCR6 is the unique receptor for the chemokine CCL20 [3], and the two are thought to be involved in various tumoral and metastatic processes [4]. The effects of CCR6 on tumor progression and prognosis are controversial, however. CCR6 expression is reportedly related to liver metastasis [4, 5], carcinogenesis, progres- sion, and aggressiveness [6, 7], and upregulated CCR6 Y. Minamiya : H. Saito : N. Takahashi : M. Ito : H. Toda : T. Ono : H. Konno : S. Motoyama : J.-i. Ogawa Department of Chest, Breast and Endoclinologic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita City 010-8543, Japan Y. Minamiya (*) Division of Thoracic Surgery, Akita University School of Medicine, 1-1-1 Hondo, Akita City 010-8543, Japan e-mail: minamiya@med.akita-u.ac.jp Tumor Biol. (2011) 32:197–202 DOI 10.1007/s13277-010-0113-x