Yuzhe Wei1, Tie Wang1, Hongjiang Song1, Lining Tian2, Gongwei Lyu3, Lei Zhao4, Yingwei Xue5. 1. Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China. 2. Department of Medical Education, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China. 3. Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China. 4. Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China. 5. Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China. Electronic address: medwang@163.com.
Abstract
BACKGROUND: Gastric cancer is a common cancer with a poor prognosis. Chemokines play important roles in the tumor microenvironments to support tumor growth and metastasis. The effects of C-C motif chemokine ligand 22 (CCL22) in gastric cancer remain unclear. MATERIALS AND METHODS: Between January 1, 2014 and April 31, 2014, a total of 298 gastric cancer patients were recruited to this study. Circulating concentrations of CCL22 were measured in gastric cancer patients before surgery, at discharged and during follow-up visits. The expression of CCL22 in gastric cancer tumor beds was measured by immunohistochemistry. The proportion of CD3+CD4+CD25+Foxp3+ regulatory T cells in tumor sites was assessed by flow cytometry. RESULTS: Gastric cancer patients had higher serum CCL22 levels compared to healthy controls (P < 0.001). Immunohistochemistry indicated that the gastric cancer tumor beds were the source of serum CCL22, as gastric cancer patients had an increased proportion of strong expression of CCL22 (P < 0.01), and immunohistochemistry scores were positively correlated with levels of circulating CCL22 (P < 0.001). Gastric cancer tissue harbored a higher percentage of regulatory T cells compared to normal tumor-free stomach margins (P < 0.001), and this abundance of regulatory T cells was positively correlated with circulating levels of CCL22 (P < 0.001). Gastric cancer patients with peritoneal metastasis showed increased levels of circulating CCL22 before surgery compared to metastasis-free patients (P < 0.001). Gastric cancer patients with the recurrence within the first year after surgery had elevated serum CCL22 concentrations at different time points compared to those of recurrence-free patients (P < 0.001). Logistic regression analysis indicated that high CCL22 circulating levels before surgery is a risk factor for peritoneal metastasis and an independent risk factor for an early recurrence after surgery. CONCLUSIONS: CCL22 plays an important role in supporting gastric cancer development presumably by increasing the percentage of regulatory T cells in the tumor microenvironments. CCL22 levels in sera have a predictive value for gastric cancer peritoneal metastasis and the early recurrence. Therefore, CCL22 may be a therapeutic target for gastric cancer.
BACKGROUND:Gastric cancer is a common cancer with a poor prognosis. Chemokines play important roles in the tumor microenvironments to support tumor growth and metastasis. The effects of C-C motif chemokine ligand 22 (CCL22) in gastric cancer remain unclear. MATERIALS AND METHODS: Between January 1, 2014 and April 31, 2014, a total of 298 gastric cancerpatients were recruited to this study. Circulating concentrations of CCL22 were measured in gastric cancerpatients before surgery, at discharged and during follow-up visits. The expression of CCL22 in gastric cancer tumor beds was measured by immunohistochemistry. The proportion of CD3+CD4+CD25+Foxp3+ regulatory T cells in tumor sites was assessed by flow cytometry. RESULTS:Gastric cancerpatients had higher serum CCL22 levels compared to healthy controls (P < 0.001). Immunohistochemistry indicated that the gastric cancer tumor beds were the source of serum CCL22, as gastric cancerpatients had an increased proportion of strong expression of CCL22 (P < 0.01), and immunohistochemistry scores were positively correlated with levels of circulating CCL22 (P < 0.001). Gastric cancer tissue harbored a higher percentage of regulatory T cells compared to normal tumor-free stomach margins (P < 0.001), and this abundance of regulatory T cells was positively correlated with circulating levels of CCL22 (P < 0.001). Gastric cancerpatients with peritoneal metastasis showed increased levels of circulating CCL22 before surgery compared to metastasis-freepatients (P < 0.001). Gastric cancerpatients with the recurrence within the first year after surgery had elevated serum CCL22 concentrations at different time points compared to those of recurrence-free patients (P < 0.001). Logistic regression analysis indicated that high CCL22 circulating levels before surgery is a risk factor for peritoneal metastasis and an independent risk factor for an early recurrence after surgery. CONCLUSIONS:CCL22 plays an important role in supporting gastric cancer development presumably by increasing the percentage of regulatory T cells in the tumor microenvironments. CCL22 levels in sera have a predictive value for gastric cancer peritoneal metastasis and the early recurrence. Therefore, CCL22 may be a therapeutic target for gastric cancer.
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