title: CX3CL1 expression is associated with poor outcome in breast cancer patients.
abstract: The significance of chemokines in cancer biology has been widely recognized in recent years. CX3CL1 is a unique subclass of chemokine with complex functions, including recruitment of anti-tumor leukocytes and promoting cancer survival, thus affecting cancer progression in both the directions. It is not clear how these different functions interact in breast cancers. This is further complicated by the heterogeneity of breast cancer, and differential association of CX3CL1 with different subgroups could be present. There is only limited knowledge of CX3CL1 expression profile, its relationship with different biological features, subtypes, and outcomes in breast cancers. In this study, CX3CL1 expression was examined in a large cohort of breast cancers by immunohistochemistry and its association with clinicopathological factors, biomarker expression, and impact on patients' survival was assessed. High CX3CL1 expression was detected in 33.3 % (252/757) of primary invasive cancers. In line with its chemo-attractant function, CX3CL1 expression correlated positively with increased tumor infiltrating lymphocytes (TIL) (p = 0.005). In addition, CX3CL1 also correlated positively with adverse features in breast cancers, including lymph node involvement (p = 0.007), high Ki67 (p = 0.002), α-B crystallin expression (p = 0.008), and luminal B (worse prognosis luminal cancers) subtype (p = 0.024). Consistently, breast cancers with high expression of CX3CL1 were found to have a poorer overall survival (χ(2) = 4.797, p = 0.029). Interestingly, the adverse effect of CX3CL1 on outcome appeared to be more prominent in cancers with low TIL. These findings indicated that CX3CL1 could also have a pro-tumor role in breast cancer, despite its previously suggested role in enhancing anti-tumor immunity. The results highlighted the complicated functions of CX3CL1 in breast carcinogenesis. Further studies are needed to clarify the relative contribution of these anti- and pro-tumor functions in order to understand the true prognostic and potential therapeutic values of CX3CL1.
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ngan Shing Street, Shatin, NT, Hong Kong.
authors.forename: Julia Y S
authors.initials: JY
authors.lastname: Tsang
authors.forename: Yun-Bi
authors.initials: YB
authors.lastname: Ni
authors.forename: Siu-Ki
authors.initials: SK
authors.lastname: Chan
authors.forename: Mu-Min
authors.initials: MM
authors.lastname: Shao
authors.forename: Ying-Kin
authors.initials: YK
authors.lastname: Kwok
authors.forename: Kit-Wing
authors.initials: KW
authors.lastname: Chan
authors.forename: Puay Hoon
authors.initials: PH
authors.lastname: Tan
authors.forename: Gary M
authors.initials: GM
authors.lastname: Tse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology*; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008875:Middle Aged; D011237:Predictive Value of Tests; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1