Coexpression of atypical chemokine binders (ACBs) in breast cancer predicts better outcomes.
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.
Zeng
Xiao-Hua
XH
Breast Cancer Institute, Cancer Hospital, Department of Oncology, Shanghai Medical College, Institutes of Biomedical Science, Fudan University, Shanghai, 200032, China.
Ou
Zhou-Luo
ZL
Yu
Ke-Da
KD
Feng
Lan-Yun
LY
Yin
Wen-Jing
WJ
Li
Jing
J
Shen
Zhen-Zhou
ZZ
Shao
Zhi-Ming
ZM
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
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