Fractalkine-CX3CR1 axis regulates tumor cell cycle and deteriorates prognosis after radical resection for hepatocellular carcinoma.
OBJECTIVE
Fractalkine is the only CX3C chemokine, and its receptor, CX3CR1, is expressed on NK cells, CD8+ T cells, monocytes, and dendritic cells (DC). Although studies have reported that fractalkine regulates the host immune response, the roles of the fractalkine-CX3CR1 axis in tumor biology and the clinical results of hepatocellular carcinoma (HCC) remain unknown.


METHODS
Fractalkine and CX3CR1 expression in HCC were evaluated and compared with the clinicopathologic features, including tumor progression determined by proliferating cell nuclear antigen (PCNA) antibody and patient prognosis after surgery.


RESULTS
Tumors with high expression of both fractalkine and CX3CR1 had significantly fewer intra- and extrahepatic recurrences, a low PCNA labeling index (PCNALI), and different histological grades. Patients with tumors that expressed both had a significantly better prognosis in terms of disease-free (DFS) and overall survival (OAS), and this finding was identified as one of the independent prognostic factors in the multivariate analysis.


CONCLUSIONS
Our results suggest that the fractalkine-CX3CR1 axis plays a pivotal role in the prognosis of patients with HCC, which might arise from the known modulation of the host immune response, and that of the cell cycle in HCC.
Matsubara
Takeshi
T
Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, Japan. nanachan@med.shimane-u.ac.jp
Ono
Takashi
T
Yamanoi
Akira
A
Tachibana
Mitsuo
M
Nagasue
Naofumi
N
D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D000073883:CX3C Chemokine Receptor 1; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000378:metabolism; D011169:Portal Vein / Q000473:pathology; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000276:immunology; D019707:Receptors, Chemokine / Q000378:metabolism*; D012307:Risk Factors
D000974:Antibodies, Antinuclear; D014408:Biomarkers, Tumor; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D019707:Receptors, Chemokine