Wei Yuzhe, Wang Tie, Song Hongjiang, Tian Lining, Lyu Gongwei, Zhao Lei, Xue Yingwei
Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
Department of Medical Education, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
J Surg Res. 2017 May 1;211:266-278. doi: 10.1016/j.jss.2016.11.067. Epub 2016 Dec 14.
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.
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 CD3CD4CD25Foxp3 regulatory T cells in tumor sites was assessed by flow cytometry.
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.
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.
胃癌是一种常见癌症，预后较差。趋化因子在肿瘤微环境中对支持肿瘤生长和转移起着重要作用。C-C基序趋化因子配体22（CCL22）在胃癌中的作用仍不清楚。
2014年1月1日至2014年4月31日，共有298例胃癌患者纳入本研究。在胃癌患者手术前、出院时及随访期间测量CCL22的循环浓度。通过免疫组织化学检测CCL22在胃癌肿瘤床中的表达。通过流式细胞术评估肿瘤部位CD3CD4CD25Foxp3调节性T细胞的比例。
与健康对照相比，胃癌患者血清CCL22水平更高（P<0.001）。免疫组织化学表明，胃癌肿瘤床是血清CCL22的来源，因为胃癌患者CCL22强表达比例增加（P<0.01），且免疫组织化学评分与循环CCL22水平呈正相关（P<0.001）。与无肿瘤的正常胃边缘相比，胃癌组织中调节性T细胞百分比更高（P<0.001），且调节性T细胞的这种丰度与CCL22循环水平呈正相关（P<0.001）。与无转移患者相比，有腹膜转移的胃癌患者术前循环CCL22水平升高（P<0.001）。与无复发患者相比，术后第一年复发的胃癌患者在不同时间点血清CCL22浓度升高（P<0.001）。逻辑回归分析表明，术前CCL22循环水平高是腹膜转移的危险因素，也是术后早期复发的独立危险因素。
CCL22可能通过增加肿瘤微环境中调节性T细胞的百分比在支持胃癌发展中起重要作用。血清中CCL22水平对胃癌腹膜转移和早期复发具有预测价值。因此，CCL22可能是胃癌的治疗靶点。
