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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
作者：余周庆  童国勇  徐佳  王曦  戈春城 
单位：恩施土家族苗族自治州中心医院 口腔科, 湖北 恩施 445000
关键词：胰岛素样生长因子结合蛋白-2 局部晚期口腔鳞状细胞癌 诱导化疗 预后 
分类号：R739.85;R453
出版年·卷·期（页码）：2022·41·第五期（695-701）
摘要：

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（χ2=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 stages Ⅰ-Ⅱ and 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 stages Ⅰ-Ⅱ OSCC 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 stage Ⅰ-Ⅱ OSCC 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 survivalχ2=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.
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