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Significant association between high serum CCL5 levels and better disease-free survival of patients with early breast cancer.

ABSTRACT: Analysis of anticancer immunity aids in assessing the prognosis of patients with breast cancer. From 250 operated breast cancers, we focused on serum levels of C-C motif chemokine ligand 5 (CCL5), which is involved in cancer immune reactions. Serum levels of CCL5 were measured using a cytometric bead-based immunoassay kit and CCL5 expression in cancer cells was determined using immunohistochemical staining. In addition, mRNA in cancer and stromal cells was analyzed by microdissection and comparison with the public dataset. Disease-free survival (DFS) of patients with high CCL5 levels (cut-off, 13.87 ng/mL; n = 192) was significantly better than those with low CCL5 levels (n = 58; hazard ratio, 0.20; 95% confidence interval, 0.10-0.39; P < .0001). An improved overall survival was observed in patients with high CCL5 levels compared to those with low CCL5 levels (P = .024). On the contrary, high immunohistochemical expression of CCL5 in cancer cells was significantly associated with decreased DFS. As serum CCL5 levels did not correlate with CCL5 expression in cancer cells and the relative expression of mRNA CCL5 was elevated in stromal cells in relation to cancer cells, serum CCL5 might be derived not from cancer cells, but from stromal cells. Expression of CCL5 in serum, but not in cancer cells, might contribute to improved patient prognosis mediating through not only immune reaction, but through other mechanisms. Determination of circulating CCL5 levels could be useful for predicting patient prognosis.

SUBMITTER: Fujimoto Y

PROVIDER: S-EPMC6942441 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Significant association between high serum CCL5 levels and better disease-free survival of patients with early breast cancer.

Fujimoto Yukie Y Inoue Natsuko N Morimoto Koji K Watanabe Takahiro T Hirota Seiichi S Imamura Michiko M Matsushita Yosuke Y Katagiri Toyomasa T Okamura Haruki H Miyoshi Yasuo Y

Cancer science 20191216 1

Analysis of anticancer immunity aids in assessing the prognosis of patients with breast cancer. From 250 operated breast cancers, we focused on serum levels of C-C motif chemokine ligand 5 (CCL5), which is involved in cancer immune reactions. Serum levels of CCL5 were measured using a cytometric bead-based immunoassay kit and CCL5 expression in cancer cells was determined using immunohistochemical staining. In addition, mRNA in cancer and stromal cells was analyzed by microdissection and compari ...[more]

PMID: 31724785

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Project description:BackgroundThe association between dyslipidaemia and breast cancer remains controversial, especially regarding the dynamic changes in lipid levels.ObjectivesThis study aimed to elucidate the role of serum lipid levels and the changes in disease outcomes in patients with breast cancer.MethodsThe lipid profiles of patients with breast cancer who underwent surgery between 2013 and 2017 were retrospectively reviewed. The lipid profiles comprised triglyceride (TG), total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein. Serum lipid levels were categorized into three groups based on the tertiles. The Wilcoxon test was used to compare changes in serum lipid levels during follow-up. Hazard ratios (HRs) for survival outcomes were estimated using a multivariate Cox regression analysis.ResultsA total of 3499 women diagnosed with nonmetastatic invasive breast cancer were included in this study, with a median follow-up of 60.4 months. We confirmed that each 1-tertile increased TG at baseline [HR = 1.19, 95% confidence interval (CI) 1.02-1.39] and 1-year follow-up (HR = 1.46, 95% CI 1.07-1.98) led to worse relapse-free survival (RFS). A lower risk of disease relapse was observed with each 1-tertile upregulation in HDL at 1-year follow-up (HR = 0.72, 95% CI 0.56-0.92). Receiving systemic therapies tends to induce an elevation in plasma lipid levels 1 year after surgery, especially in terms of TG. Regarding the prognostic value of dynamic changes in lipid levels, patients with sustained high levels of TG had poorer RFS (HR = 1.90, 95% CI 1.16-3.11), whereas maintaining high levels of HDL led to better survival (HR = 0.60, 95% CI 0.37-0.97).ConclusionHigh TG at baseline and during follow-up was associated with worse disease outcome in early breast cancer patients. Systemic treatment would lead to an elevation of serum lipid levels. Patients with sustained high HDL level at 1-year follow-up after surgery had a superior prognosis, warranting further clinical evaluation.

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Significant association between high serum CCL5 levels and better disease-free survival of patients with early breast cancer.

Publications

Significant association between high serum CCL5 levels and better disease-free survival of patients with early breast cancer.

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