目的 通过观察鸟苷酸结合蛋白 5(GBP5)、免疫细胞在肿瘤细胞和间质细胞中的表达,探讨 GBP5 表达对头颈部鳞 状细胞癌(HNSCC)治疗后的影响。 方法 回顾性选取 2019 年 8 月至 2023 年 1 月就诊于河北北方学院附属第一医院放疗科的 HNSCC 患者(n = 87),采用免疫组化法观察 GBP5、程序性死亡受体配体 1(PD-L1)的表达,采用流式细胞仪检测免疫细胞的 水平。 结果 经 TCGA 数据库筛选的 GBP5 与免疫浸润评分均呈正相关。 在肿瘤细胞和间质细胞中,GBP5 阳性表达率分别为 58. 6%(51 / 87)和 42. 5%(37 / 87),差异显著(χ 2 = 16. 805,P<0. 001)。 GBP5 阳性和阴性表达患者 pTNM 分期、PD-L1 表达有 差异(P 均<0. 05);间质细胞 GBP5 阳性表达患者 CD3、CD4、CD8、CD20、CD68 水平显著高于 GBP5 阴性表达患者,而前者的 CD163 水平明显低于后者(P 均<0. 05)。 GBP5 表达与 PD-L1 表达、CD8、CD68 细胞水平密切相关(P 均<0. 05)。 单因素和多 因素 Cox 比例风险回归模型分析结果显示,间质细胞中 GBP5 阴性表达(HR = 4. 66) 是 HNSCC 的不良预后因素( P = 0. 005),而肿瘤细胞 GBP5 阴性联合间质细胞 GBP5 阳性表达(HR= 0. 04)、CD68(HR= 0. 21)均是 HNSCC 的独立保护因素(P 均<0. 05)。 CD68 水平联合间质细胞 GBP5 表达评估 HNSCC 预后的敏感度为 0. 82,特异度为 0. 90,曲线下面积值 0. 81,具有 良好的诊断性能(P<0. 05)。 间质细胞 GBP5 阳性表达者中位肿瘤特异性生存期明显优于阴性表达者(1620 d 比 850 d,HR = 0. 15,95%CI = 0. 05~ 0. 42,P= 0. 001);分层分析显示,肿瘤细胞 GBP5 阴性表达和间质细胞 GBP5 阳性表达者的中位肿瘤特异 性生存期最优(1620 d)。 在 CD68 高水平亚组分析中,间质细胞 GBP5 阳性者中位肿瘤特异性生存期明显优于阴性者(1620 d 比 850 d)。 不同 PD-L1 表达水平的亚组分析中,相对于间质细胞 GBP5 阴性表达,阳性表达的中位肿瘤特异性生存期显著延 长(P 均<0. 05)。 结论 间质细胞中 GBP5 表达与免疫细胞 CD86 水平可能相关,相对于肿瘤细胞,可能作为 PD-L1 阴性患者 的补充标志物。

Objective Investigate the effect of guanylate binding protein GBP 5 expression on the treatment of head and neck squamous cell carcinoma HNSCC by observing the expression of GBP5 and immune - infiltrating cells in tumor and stromal cells. Method The correlation between GBP5 and immune-infiltrating score was analyzed by bioinformatics. 87 patients treated with HNSCC in the radiotherapy department of the first affiliated hospital of Hebei North University from August 2019 to January 2023 were analyzed retrospectively. Immunohistochemistry was used to observe the expression of GBP5 and programmed death-ligand 1 PDL1 flow cytometry was examined to immune-infiltrating cells. Result There was positive correlation between immune-infiltrating score and GBP5 which was screened from TCGA database. In tumor and stromal cells the positive expression rate of GBP5 was 58. 6% 51 / 87 and 42. 5% 37 / 87 respectively with significant difference in statistics χ 2 = 16. 805 P<0. 001 . There were statistically significant differences in pTNM stage PD-L1 between the positive and negative expressions of GBP5 all P<0. 05 . The levels of CD3 CD4 CD8 CD20 and CD68 in the positive expression of GBP5 were higher than those in the negative expression of GBP5 in stromal cells while the former was obviously lower than that in the latter in CD163 all P< 0. 05 . The expression of GBP5 was associated with PD-L1 expression CD8 CD68 cells respectively all P<0. 05 . Univariate and multivariate Cox regression analysis showed that the negative expression of GBP5 in stromal cells HR = 4. 66 was a poor factor for HNSCC prognosis P = 0. 005 however the negative expression of GBP5 in tumor cells and positive expression of GBP5 in stromal cells HR= 0. 04 CD68 HR= 0. 21 were protective factors for HNSCC all P<0. 05 . The sensitivity of CD68 level combined with GBP5 expression in stromal cells in evaluating the prognosis of HNSCC was 0. 82 the specificity was 0. 90 AUC was 0. 81 which was good diagnostic ability P< 0. 05 . The median tumor-specific survival rate of the positive expression of GBP5 was significantly better than that of the negative expression of GBP5 1620 d vs. 850 d HR = 0. 15 95% CI = 0. 05- 0. 42 P = 0. 001 . Stratified analysis showed that the median tumor-specific survival rate was optimal for the negative expression of GBP5 in tumor cells combined with positive expression of GBP5 in stromal cells 1620 d . In the analysis of high-level of CD68 subgroup the median tumor-specific survival rate was better in positive expression of GBP5 than that in negative expression of GBP5 in stromal cells 1620 d vs. 850 d . In the analysis of the subgroup with high and low expressions of PD-L1 the median tumor-specific survival rate in the positive expression of GBP5 was significantly longer compared to the negative expression of GBP5. Conclusion The expression of GBP5 in stromal cells might be closely related to CD68 levels which may serve as a supplementary marker for negative expression of PD-L1 compared to that in tumor cells.