口腔鳞状细胞癌RARRES2表达和中性粒细胞浸润与预后关系

CORRELATION BETWEEN RARRES2 EXPRESSION AND NEUTROPHIL INFILTRATION IN ORAL SQUAMOUS CELL CARCINOMA AND THEIR RELATIONSHIP WITH PROGNOSIS

目的探讨口腔鳞状细胞癌(OSCC)组织视黄酸受体反应蛋白(RARRES2)的表达及其与中性粒细胞浸润密度的关系,并分析其与临床病理特征及预后的关系。方法应用免疫组织化学方法,检测74例OSCC组织标本及其对应的癌旁正常组织中RARRES2表达和中性粒细胞浸润情况,Spearman相关分析RARRES2表达和中性粒细胞密度之间的关系,Transwell实验检测RARRES2对中性粒细胞趋化能力的影响。应用Mann-Whitney检验分析RARRES2表达和中性粒细胞密度与临床病理因素的关系,Kaplan-Meier法和Log-rank检验进行生存分析,Cox回归模型分析影响OSCC生存的危险因素。结果免疫组织化学检测结果显示,OSCC组织RARRES2表达显著高于癌旁组织(Z=-6.091,P<0.01),RARRES2高表达的OSCC组织区域中性粒细胞浸润的密度高于RARRES2相对低表达的癌组织区域(U=433.5,P<0.05)。Transwell结果显示,重组RAREES2对中性粒细胞样细胞有明显趋化作用。Spearman相关分析显示,RARRES2的表达和中性粒细胞浸润呈正相关(r=0.309,P<0.05)。Mann-Whitney分析显示,OSCC组织RARRES2高表达且中性粒细胞高密度与淋巴结转移(Z=-4.789,P<0.01)、TNM分期(Z=-4.293,P<0.01)和肿瘤复发(Z=-2.578,P<0.01)相关。生存分析显示,RARRES2高表达且中性粒细胞高密度的OSCC病人术后总体生存时间和无病生存时间更短(P=0.001~0.017)。Cox多因素回归分析表明,RARRES2高表达且中性粒细胞高密度是影响OSCC病人术后总体生存时间和无病生存时间的独立预后因素(P=0.031、0.003)。结论RARRES2高表达且中性粒细胞高密度提示OSCC病人预后不良,二者可作为判断OSCC病人预后的潜在指标。OSCC组织中RARRES2高表达可以趋化更多中性粒细胞浸润。

Objective To explore the correlation between the expression of retinoic acid receptor responder protein(RARRES2)and neutrophil infiltration density in oral squamous cell carcinoma(OSCC)tissue,and to analyze their relationship with the clinicopathological characteristics and prognosis.Methods Immunohistochemical methods were used to determine RARRES2 expression and neutrophil infiltration in 74 OSCC tissue specimens and their corresponding normal paracancerous tissues,Spearman correlation analysis was used to assess the relationship between RARRES2 expression and neutrophil density,and Transwell assay was used to determine the effect of RARRES2 on the chemotaxis of neutrophils.Mann-Whitney test was used to analyze the relationship of RARRES2 expression and neutrophil density with clinicopathological factors,the Kaplan-Meier method and Log-rank test were used for survival analysis,and the Cox regression model was used to analyze the risk factors affecting OSCC survival.Results The immunohistochemical assay showed that the RARRES2 expression in the OSCC tissues was significantly higher than that in the paracancerous tissues(Z=-6.091,P<0.01)and the neutrophil infiltration density in the OSCC tissues with high RARRES2 expression was higher than that in cancerous tissues with relatively low RARRES2 expression(U=433.5,P<0.05).Transwell results showed that recombinant RAREES2 had a significant chemotactic effect on neutrophil-like cells.Spearman correlation analysis showed that RARRES2 expression was positively correlated with neutrophil infiltration(r=0.309,P<0.05).Mann-Whitney analysis showed that high RARRES2 expression and high neutrophil density were correlated with lymph node metastasis(Z=-4.789,P<0.01),TNM staging(Z=-4.293,P<0.01),and tumor recurrence(Z=-2.578,P<0.01).The survival analysis showed that OSCC patients with high RARRES2 expression and high neutrophil density had significantly shorter overall survival time and disease-free survival time after surgery ( P = 0.001 to 0.017);the Cox multivariate regression analysis showed that high RARRES2 expression and high neutrophil density were independent prognostic factors influencing the overall survival time and disease-free survival time of OSCC patients after surgery ( P =0.031,0.003). Conclusion High RARRES2 expression and high neutrophil density indicate a poor prognosis of OSCC patients, both of which can be used as potential indicators for the prognosis of OSCC patients. High RARRES2 expression in the OSCC tissues can result in chemotaxis of increased neutrophil infiltration.