IGFBP-2预测局部晚期口腔鳞状细胞癌预后和化疗反应的临床价值

Clinical value of IGFBP-2 on predicting the prognosis and chemotherapy response in locally advanced oral squamous cell carcinoma

目的:探讨血清胰岛素样生长因子结合蛋白-2(IGFBP-2)在局部晚期口腔鳞状细胞癌(OSCC)中的临床价值,并观察其与诱导化疗及预后的关系。方法:2012年1月至2017年5月选择143例局部晚期OSCC患者为研究对象,均接受多西紫杉醇、顺铂和5-氟尿嘧啶诱导化疗。此外,还纳入了129例临床分期为Ⅰ~Ⅱ期的OSCC患者和152例健康对照者(包含20例接受整容手术者的正常口腔组织)。在局部晚期OSCC患者和Ⅰ~Ⅱ期OSCC患者中各随机选取20例肿瘤病理组织,采用免疫组化法和酶联免疫吸附测定检测组织和血清IGFBP-2表达。结果:局部晚期OSCC组织中IGFBP-2蛋白阳性表达率[80.0%(16/20)]、血清IGFBP-2水平[423.28(338.52,534.36)ng·ml^(-1)]均高于健康对照组和Ⅰ~Ⅱ期OSCC组(P<0.001)。经受试者工作特征曲线分析血清IGFBP-2用于诊断OSCC以及区分局部晚期OSCC的曲线下面积(AUC)分别为0.844(95%CI 0.807~0.880)、0.954(95%CI 0.932~0.975)。治疗后,局部晚期OSCC组97例患者病情缓解(有反应亚组)。无反应亚组患者治疗前血清IGFBP-2水平显著高于有反应亚组(P<0.001)。治疗前血清IGFBP-2在预测疗效方面的AUC值为0.776(95%CI 0.699~0.853)。生存分析显示,与低表达亚组患者相比,高表达亚组患者总生存时间较短(χ^(2)=39.474,P<0.001)。血清IGFBP-2水平升高是晚期OSCC患者总生存预后不良的独立危险因素(P<0.001)。结论:血清IGFBP-2水平可能是局部晚期OSCC患者化疗和预后评估的生物标志物,但其机制仍有待讨论。

Objective:To investigate the clinical value of serum insulin-like growth factor binding protein-2(IGFBP-2)in locally advanced oral squamous cell carcinoma(OSCC),and to observe its relationship with induction chemotherapy and prognosis.Methods:From January 2012 to may 2017,143 patients with locally advanced OSCC were selected as the study subjects,and received docetaxel,cisplatin and 5-fluorouracil induction chemotherapy.In addition,129 OSCC patients with clinical stagesⅠ-Ⅱand 152 healthy controls(including the normal oral tissue of 20 patients undergoing cosmetic surgery)were included.Each 20 tumor pathological tissues from the locally advanced OSCC patients or stagesⅠ-ⅡOSCC patients were randomly selected,and the immunohistochemistry and enzyme-linked immunosorbent assay were used to detect the expression of IGFBP-2.Results:The positive expression rate of IGFBP-2 protein[80.0%(16/20)]and serum IGFBP-2 level[423.28(338.52,534.36)ng·ml^(-1)]in locally advanced OSCC tissues were higher than those in healthy control group and stageⅠ-ⅡOSCC group(P<0.001).The area under the curve(AUC)of receiver operating characteristic curve analysis of serum IGFBP-2 for diagnosing OSCC and distinguishing locally advanced OSCC were 0.844(95%CI 0.807-0.880)and 0.954(95%CI 0.932-0.975),respectively.After treatment,97 patients in the locally advanced OSCC group were in remission(reactive subgroup).The level of serum IGFBP-2 in non-reactive subgroup was significantly higher than that in reactive subgroup(P<0.001).The AUC of serum IGFBP-2 before treatment in predicting curative effect was 0.776(95%CI 0.699-0.853).Survival analysis showed that compared with patients in the low expression subgroup,patients in the high expression subgroup had poor overall survival(χ^(2)=39.474,P<0.001).The increase of serum IGFBP-2 level was an independent risk factor for the poor overall survival in patients with advanced OSCC(P<0.001).Conclusion:Serum IGFBP-2 level may be a biomarker for chemotherapy and prognosis evaluation in patients with locally advanced OSCC,but its mechanism remains to be discussed.