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J Thorac Dis ; 11(3): 777-787, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31019765


Background: The expression of CCL28 and its relationship with clinical outcomes remain unclear in the setting of heterogeneous breast cancer. The purpose of the current study was to identify the expression characteristics of chemokine CCL28 in breast cancer, with a focus on its prognostic relevance to different subtypes. Methods: First, we investigated the expression of CCL28 in 150 breast cancer patients immunohistochemically and assessed the impact of CCL28 on relapse-free survival (RFS) in the whole cohort and different clinical subtypes [defined by hormone receptor (HR), and HER-2 status] by univariate and multivariate analysis. Furthermore, the other two cohorts comprised of 863 patients from the Cancer Genome Atlas (TCGA) database and 1,764 patients from the Kaplan-Meier plotter database, respectively, were chosen to validate the prognostic values of CCL28 in breast cancer. Results: Those with positive CCL28 expression had improved RFS in luminal-like (HR positive, any HER-2 status) subtype (P=0.052) but had impaired RFS in triple-negative cases (P=0.019), after adjustment with tumor size and lymph node status. Consistently, multivariate analysis in the TCGA cohort revealed improved disease-free survival (DFS) among patients with high expression of CCL28 in luminal-like subtype (P=0.043) and decreased DFS in patients expressing high CCL28 in triple-negative cases (P=0.010). The subsequent analysis of the Kaplan-Meier plotter cohort also demonstrated that CCL28 was a favorable prognostic factor for luminal-like cases [luminal A (P<0.001) and luminal B (P=0.031)], but a poor prognostic indicator for the patients with triple-negative phenotype (P<0.001). Conclusions: CCL28 was a favorable prognostic factor for luminal-like cases and detrimental for triple-negative subtype, indicating that the same chemokine may play different or even opposite roles in the recurrence and metastasis of different molecular subtypes of breast cancer.

Oncotarget ; 7(19): 28570-8, 2016 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-27086913


PURPOSE: The association chemokine receptor CCR3 with breast cancer subtypes and relapse-free survival is unknown. RESULTS: The overall expression (either intratumoral or peritumoral) of CCR3 was not associated with tumor size, lymph node status, age, and subtype. When we confined the analysis in samples without peritumoral stromal CCR3 expression, intratumoral expression of CCR3 was associated with breast cancer subtype (P=0.04). Tumors with high expression of CCR3 were more likely to be luminal-like rather than TNBC or HER2-enriched cancers. Moreover, high mRNA expression of CCR3 was related with improved relapse-free survival in luminal-A/B (P<0.001). The subsequent sensitivity analysis using the systemically untreated patients confirmed that higher mRNA expression of CCR3 was a robust prognostic factor for luminal-A (P=0.0025) and luminal-B (P=0.088), but not for HER2-enriched (P=0.21) and TNBC (P=0.86). In the independent cohort, the positive association between increased expression of CCR3 and improved distant relapse-free survival was also observed. METHODS: We determined the expression level of CCR3 in 150 cases with breast cancer by using immunohistochemistry (IHC) assay, for both intratumoral and peritumoral stroma, and investigated the effect of CCR3 expression on relapse-free survival according to subtype using cases from publicly available datasets, in the whole group (N=3557) and in the patients without adjuvant systemic treatment (N=1005), respectively. Moreover, the survival outcomes were validated in another independent cohort including 508 breast cancer patients treated with neoadjuvant chemotherapy. CONCLUSIONS: Our data indicate that intratumoral expression of CCR3 in breast cancer is associated with improved relapse-free survival in patients with luminal-like disease.

Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Receptores CCR3/genética , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Receptor ErbB-2/metabolismo , Receptores CCR3/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Adulto Jovem