Chemerin对口腔鳞癌中性粒细胞浸润的影响及机制探讨

doi:10.19439/j.sjos.2023.02.009

上海口腔医学 ›› 2023, Vol. 32 ›› Issue (2): 158-165.doi: 10.19439/j.sjos.2023.02.009

Chemerin对口腔鳞癌中性粒细胞浸润的影响及机制探讨

胡小媛^1,2, 王宁³, 张晓野⁴, 杨茜³, 高菲³, 王成勤³, 尚伟¹, 项锋钢^3,*, 冯元勇^1,*

1.青岛大学附属医院口腔颌面外科,山东青岛 266000;
2.昆明医科大学第三附属医院生物治疗中心,云南昆明 650000;
3.青岛大学基础医学院病理学系,山东青岛 266000;
4.山东中医药大学第二附属医院病理科,山东济南 250001

收稿日期:2021-01-12 修回日期:2021-06-13 出版日期:2023-04-25 发布日期:2023-06-13
通讯作者: 冯元勇,E-mail：feng_yuanyong@163.com; 项锋钢,E-mail：xiangfenggang@163.com。^*共同通信作者
作者简介:胡小媛（1994-）,女,硕士, E-mail：huxiaoyuan0821@163.com
基金资助:
国家自然科学基金（81702677,81602320）

Chemerin mediated neutrophil infiltration in oral squamous cell carcinoma and predicted poor prognosis

HU Xiao-yuan^1,2, WANG Ning³, ZHANG Xiao-ye⁴, YANG Qian³, GAO Fei³, WANG Cheng-qin³, SHANG Wei¹, XIANG Feng-gang³, FENG Yuan-yong¹

1. Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Qingdao University. Qingdao 266000, Shandong Province;
2. Biological Therapy Center, The Third Affiliated Hospital of Kunming Medical University. Kunming 650000, Yunnan Province;
3. Department of Pathology, School of Basic Medicine, Qingdao University. Qingdao 266000, Shandong Province;
4. Department of Pathology,The Second Affiliated Hospital of Shangdong University Traditional Chinese Medicine. Jinan 250001, Shandong Province, China

Received:2021-01-12 Revised:2021-06-13 Online:2023-04-25 Published:2023-06-13

摘要/Abstract

摘要： 目的: 探讨Chemerin对口腔鳞癌（OSCC）组织中性粒细胞浸润的影响及其可能的分子机制。方法: 应用免疫组织化学双染色方法,探讨中性粒细胞浸润与Chemerin表达之间的关系。利用Transwell实验、实时定量PCR（qRT-PCR）、蛋白质印迹法（Western blot）、酶联免疫吸附法（ELISA）和流式细胞术检测Chemerin对中性粒细胞的趋化作用。采用SPSS 23.0软件包对数据进行统计学分析。Chemerin表达和中性粒细胞密度之间的关系采用Spearman等级相关分析法,ChemR23的敲除效率、趋化指数的计算采用方差分析,Chemerin表达和中性粒细胞密度与临床病理因素的关系采用Mann-Whitney检验,生存分析采用Kaplan-Meier法和Log rank检验,OSCC生存的危险因素采用Cox回归模型。结果: 免疫组织化学双染色结果显示,Chemerin高表达与口腔鳞癌组织内中性粒细胞浸润密度呈正相关（P=0.023）,Chemerin高表达且中性粒细胞高密度与临床分期（P<0.001）、颈淋巴结转移（P<0.001）和肿瘤复发相关（P=0.002）。Kaplan-Meier生存分析表明,Chemerin高表达且中性粒细胞高密度组患者较其他2组的癌症相关总体生存期和无瘤生存期显著缩短。Transwell结果显示,OSCC 细胞和重组Chemerin对dHL-60细胞有明显趋化作用;敲除dHL-60细胞上的ChemR23后,抑制了Chemerin对dHL-60细胞的趋化作用。结论: 口腔鳞癌组织中Chemerin过表达,可通过受体ChemR23,趋化更多中性粒细胞浸润且与不良临床预后有关。

关键词: Chemerin, 中性粒细胞, 口腔鳞癌, ChemR23

Abstract: PURPOSE: To explore the effect of Chemerin in oral squamous cell carcinoma (OSCC) tissue on neutrophils infiltration and its possible molecular mechanism. METHODS: The relationship between Chemerin expression and neutrophils density was assessed via double immunohistochemistry staining.The chemotactic effect of Chemerin on neutrophils in OSCC was detected by transwell assay, real-time quantitative PCR(qRT-PCR), Western blot, enzyme-linked immunosorbent assay(ELISA) and flow cytometry. The data were statistically analyzed using SPSS 23.0 software package. The relationship between Chemerin expression and neutrophils density was assessed using Spearman rank correlation analysis. ChemR23 knockout efficiency and chemotactic index were calculated by ANOVA. The relationship between Chemerin expression, neutrophils density and clinicopathological factors was analyzed by Mann-Whitney test. Kaplan-Meier test and Log rank test were used for survival analysis, and risk factors affecting the survival of OSCC patients was assessed using Cox regression model. RESULTS: Double immunohistochemistry staining showed that overexpression of Chemerin was significantly correlated with increased neutrophils infiltration in OSCC(P=0.023), and strong Chemerin expression and high neutrophils density were associated with higher clinical stage(P<0.001), cervical lymph node metastasis (P<0.001) and tumor recurrence (P=0.002). Kaplan-Meier survival analysis showed that patients in the strong Chemerin expression + high neutrophils density group had shortened cancer-related overall survival time and disease-free survival time compared with the other two groups. Transwell assay results showed that both OSCC cells and R-Chemerin had a significant chemotactic effect on dHL-60 cells; knockdown of ChemR23 suppressed Chemerin-induced chemotaxis to dHL-60 cells. CONCLUSIONS: Overexpression of Chemerin in OSCC tissue chemoattracts more neutrophils to tumor sites through its receptor ChemR23 and is related to poor clinical prognosis.

Key words: Chemerin, Neutrophils, Oral squamous cell carcinoma, ChemR23

中图分类号:

R739.8

胡小媛, 王宁, 张晓野, 杨茜, 高菲, 王成勤, 尚伟, 项锋钢, 冯元勇. Chemerin对口腔鳞癌中性粒细胞浸润的影响及机制探讨[J]. 上海口腔医学, 2023, 32(2): 158-165.

HU Xiao-yuan, WANG Ning, ZHANG Xiao-ye, YANG Qian, GAO Fei, WANG Cheng-qin, SHANG Wei, XIANG Feng-gang, FENG Yuan-yong. Chemerin mediated neutrophil infiltration in oral squamous cell carcinoma and predicted poor prognosis[J]. Shanghai Journal of Stomatology, 2023, 32(2): 158-165.

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Chemerin对口腔鳞癌中性粒细胞浸润的影响及机制探讨

Chemerin mediated neutrophil infiltration in oral squamous cell carcinoma and predicted poor prognosis

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