title: Prognostic value of CC-chemokine receptor seven expression in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor.
abstract: CC-chemokine receptor seven (CCR7), a G-protein coupled receptor normally facilitating immune cells lymphatic homing, has recently been identified on several cancer cells in promoting invasion and lymphatic specific metastasis by mimicking normal leukocytes. As tyrosine kinase inhibitors for metastatic renal cell carcinoma (mRCC) mostly emphasized on vascular inhibition, whether the CCR7 expressing tumor cells with potential lymphatic invasion function could have an impact on mRCC patient's drug response and survival, was unknown.
  
  
  
  In this study, in a clinical aspect, we retrospectively investigated the prognostic and predictive impact of tumoral CCR7 expression in 110 mRCC patients treated with sunitinib and sorafenib, and its correlation with pre- or post-administration lymphatic involvement. Immunohistochemistry on tissue microarrays were conducted for CCR7 expression evaluation.
  
  
  
  Kaplan-Meier and univariate analyses suggested high tumoral CCR7 expression as an adverse prognosticator for mRCC patients' overall survival (OS), which was further confirmed in the multivariate analyses (P = 0.002, P = 0.003 for bootstrap). This molecule could be combined with Heng's risk model for better patient OS prediction. High tumoral CCR7 expression was also an independent dismal predictor for patients' progression free survival (PFS) (P = 0.010, P = 0.013 for bootstrap), and correlated with poorer best drug response. Moreover, a possible correlation of CCR7 high expression and patients' baseline and post-administration lymph node metastasis was found.
  
  
  
  High tumoral CCR7 expression correlated with potential lymphatic involvement and poor prognosis of mRCC patients treated with tyrosine kinase inhibitors. Further external validations and basic researches were needed to confirm these results.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Bai
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xi
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Mailbox 103, 138 Yixueyuan Road, Shanghai, 200032, China. jjxufdu@fudan.edu.cn.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. guo.jianming@zs-hospital.sh.cn.
authors.forename: Jianming
authors.initials: J
authors.lastname: Guo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012372:ROC Curve; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C515370:CCR7 protein, human; D047428:Protein Kinase Inhibitors; D054400:Receptors, CCR7
keywords: CC-chemokine receptor 7; Lymphatic invasion; Metastatic renal cell carcinoma; Overall survival; Progression free survival