title: CXCR4 and CXCL12 immunoreactivities differentiate primary non-small-cell lung cancer with or without brain metastases.
abstract: Synchronous or metachronous brain metastases (BMs) occur in about 33% of patients affected by non-small-cell lung cancer (NSCLC). To date, no reliable biological marker is able to identify patients who will develop BMs. In the present study, using a quantitative double-labeling immunofluorescence analysis, we evaluated the expression of chemokine CXCL12 and its receptor, CXCR4, in primary NSCLC histological specimens of patients with and without BMs. The immunoreactivity of CXCL12 and CXCR4 was significantly higher in NSCLC samples of patients with BMs. We performed Receiver Operating Characteristics (ROC) analysis in order to define optimal cut-off values for CXCL12 and CXCR4 immunoreactivity that could discriminate between NSCLC patients without and with BMs. ROC curves showed a good diagnostic accuracy and adequate predictive power for both CXCL12 and CXCR4. These findings suggest a possible role for the CXCL12/CXCR4 axis in the metastatic evolution of NSCLC, and its potential use as prognostic markers and drug targets.
authors.affiliation: Functional Genomics Center, Institute of Neurological Sciences, Italian National Research Council, Catania, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Paratore
authors.forename: Giuseppe Luigi
authors.initials: GL
authors.lastname: Banna
authors.forename: Maria
authors.initials: M
authors.lastname: D'Arrigo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Saita
authors.forename: Rosario
authors.initials: R
authors.lastname: Iemmolo
authors.forename: Letizia
authors.initials: L
authors.lastname: Lucenti
authors.forename: Domenico
authors.initials: D
authors.lastname: Bellia
authors.forename: Helga
authors.initials: H
authors.lastname: Lipari
authors.forename: Calogero
authors.initials: C
authors.lastname: Buscarino
authors.forename: Rosario
authors.initials: R
authors.lastname: Cunsolo
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Cavallaro
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D054377:Chemokine CXCL12 / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D019718:Receptors, CXCR4 / Q000032:analysis / Q000096:biosynthesis*; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4