title: Coexpression of atypical chemokine binders (ACBs) in breast cancer predicts better outcomes.
abstract: Some evidence suggests that atypical chemokine binders (ACBs) including DARC, D6, and CCX-CKR play an important role in inhibiting invasion and metastasis of cancer cells; however, their expression in breast cancer has not been well characterized. The purpose of this study was to determine the predictive value of ACBs for relapse-free survival and overall survival in breast cancer. The expressions of the three molecules were analyzed immunohistochemically in a total of 558 consecutive breast specimens comprising 12 normal breast tissues, 29 noninvasive (carcinoma in situ), and 517 invasive breast carcinoma and their relationships to clinicopathological features and survival were investigated in invasive breast cancer. Coexpression of ACBs in invasive breast carcinoma (55.9%) was much lower that of noninvasive breast carcinoma (93.1%) and normal breast tissue (100.0%), P = 0.0004, 0.0096, respectively. Their separate stainings in invasive cancer were significantly conversely correlated with lymph node status and tumor stage. In univariate analysis, the three proteins and their coexpression were significantly associated with higher relapse-free survival and overall survival. In multivariate analysis, each of these molecules was favorable for relapse-free survival, but not overall survival. Surprisingly, their coexpression was not only independently prognostic factor for relapse-free survival (RR = 0.182, 95% CI: 0.101-0.327, P < 0.001), but also for overall survival (RR = 0.271, 95% CI: 0.081-0.910, P = 0.035). These findings highlight that the multiple loss of ACBs may occur during the development of tumorigenesis and their coexpression in breast cancer is predictive of favorable outcomes.
authors.affiliation: Breast Cancer Institute, Cancer Hospital, Department of Oncology, Shanghai Medical College, Institutes of Biomedical Science, Fudan University, Shanghai, 200032, China.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Zeng
authors.forename: Zhou-Luo
authors.initials: ZL
authors.lastname: Ou
authors.forename: Ke-Da
authors.initials: KD
authors.lastname: Yu
authors.forename: Lan-Yun
authors.initials: LY
authors.lastname: Feng
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Yin
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Shen
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000628:therapy*; D018925:Chemokines / Q000378:metabolism*; D004375:Duffy Blood-Group System / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008593:Menopause; D008875:Middle Aged; D054388:Receptors, CCR / Q000096:biosynthesis; D054447:Receptors, CCR10 / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D016896:Treatment Outcome; D000097628:Chemokine Receptor D6
chemical_list: D018925:Chemokines; D004375:Duffy Blood-Group System; D054388:Receptors, CCR; D054447:Receptors, CCR10; D011956:Receptors, Cell Surface; D000097628:Chemokine Receptor D6; C473745:ACKR1 protein, human; C408223:ACKR4 protein, human