结直肠癌患者外周血MDSCs与S100A9水平及其临床意义探讨

A study on the correlation between peripheral blood MDSCs and serum S100A9 level and their clinical significance in patients with colorectal cancer

摘要:

目的：检测结直肠癌（colorectal cancer，CRC）患者外周血中髓源性抑制细胞（myeloid-derived suppressor cells，MDSCs）含量及血清S100A9蛋白的水平，分析两者之间的相关性，探讨其在临床诊疗中的潜在应用价值。方法：收集82例临床外周血样本及相关电子病例，其中CRC患者52例，健康者30例。采用流式检测外周血单个核细胞（peripheral blood mononuclear cell，PBMC）中MDSCs的频数，双抗体夹心酶联免疫吸附试验（ELISA）检测血清S100A9水平，用SPSS及Graphpad Prism 进行Mann-Whitney 检验分析，Spearmanr分析和ROC曲线分析。结果：CRC患者外周血MDSCs以及血清S100A9水平均明显高于健康对照组（P＜0.01），且血清S100A9蛋白水平和外周血中MDSCs的频数两者之间存在正相关（r=0.38，P=0.01）；同时相比于Dukes分期中的A/B期和未发生转移的患者，处于C/D期和伴淋巴结转移2组患者血清中的S100A9水平及MDSCs频数明显升高，并具有统计学意义（P＜0.01）；并且两者的ROC曲线下面积AUC＞0.7（P<0.01），说明两者对诊断CRC以及评估CRC患者分期情况和是否发生转移均具有较好的诊断价值。结论：CRC患者外周血PBMC中MDSCs的频数与血清S100A9蛋白均明显升高；两者均有望成为CRC分期和淋巴结转移的标志物。

Abstract:

Objective：To measure the frequency of myeloid-derived suppressor cells（MDSCs） in peripheral blood and serum S100A9 level in patients with colorectal cancer（CRC），to analyze the correlation between the two indices，and to investigate their potential application in the clinical diagnosis and treatment. Methods：A total of 82 clinical peripheral blood samples （including 52 samples from patients with CRC and 30 samples from healthy subjects[as controls]） and related electronic medical records were collected. The frequency of MDSCs in peripheral blood mononuclear cells（PBMCs） was measured by flow cytometry. The serum S100A9 level was measured by a double antibody sandwich enzyme-linked immunosorbent assay. SPSS and Graphpad Prism were used for the Mann-Whitney test，Spearman R analysis，and receiver operating characteristic（ROC） curve analysis. Results：Compared with the controls，the patients with CRC had significantly increased frequency of MDSCs in PBMCs and serum S100A9 level（P<0.01），with a positive correlation between MDSC frequency and serum S100A9 level（r=0.38，P=0.01）. Compared with the patients who were at Dukes’ stage A/B and without any lymph node metastasis，the patients who were at Dukes’ stage C/D and with lymph node metastasis had significantly increased MDSC frequency and serum S100A9 level（P<0.01）；meanwhile，the area under the ROC curve was greater than 0.7 for both of the above indices（P<0.01），indicat－ing that both indices exhibited a favorable value in the diagnosis of CRC and the evaluation of the stage and metastasis of CRC. Conclusion：Patients with CRC have a significantly increased frequency of MDSCs in PBMCs and serum S100A9 level；therefore，both indices may be potential biomarkers that can contribute to the staging of CRC and predict the metastasis of CRC.