血浆载脂蛋白E在甲状腺乳头状癌发生淋巴结转移中的作用

The role of plasma apolipoprotein E in the occurrence and lymph node metastasis of papillary thyroid cancinoma

目的探讨APOE在PTC发生及淋巴结转移(LNM)中的作用。方法回顾性分析2019年9月至2022年9月于河北北方学院附属第一医院耳鼻咽喉头颈外科经手术治疗且病理确诊的161例PTC患者(PTC组)和31例结节性甲状腺肿患者(对照组)临床资料。根据术后病理结果将PTC患者分为LNM组(PTC伴淋巴结转移,n=51)和单纯PTC组(PTC不伴淋巴结转移,n=110)。按照APOE中位数水平将PTC组分为:高水平组(>128.90 ng/L,n=80)及低水平组(≤128.90 ng/L,n=81)。通过酶联免疫吸附实验(ELISA)测定患者血浆中APOE的浓度。采用多因素Logistic回归对两组间基线资料、脂代谢相关指标及APOE蛋白水平与PTC及LNM关系进行单因素及多因素分析。绘制ROC曲线评价APOE对PTC发生的预测价值。采用TIMER数据库分析APOE基因在泛癌与癌旁正常组织中的表达差异以及APOE表达与免疫细胞浸润之间的相关性。结果PTC组APOE水平明显高于对照组(P<0.05),HDL⁃C、APOA1低于对照组(P<0.05)。多因素Logistic分析显示:APOE是预测PTC发生发展的独立危险因素(P=0.022)。APOE预测PTC发生的AUC为0.639,诊断临界值为109.99 ng/L,灵敏度为81.4%,特异度为48.4%。LNM组APOE水平明显高于单纯PTC组(P=0.022)。APOE、年龄、LP(a)与PTC发生LNM明显相关(P<0.05)。淋巴结转移数目越多,APOE的水平越高(OR=1.286,95%CI:1.033~1.602,P<0.05)。TIMER数据库分析结果显示:与癌旁正常组织相比,APOE在甲状腺癌中高表达(P<0.01),且与B细胞、中性粒细胞、CD8+T细胞、CD4+T细胞、巨噬细胞、树突状细胞表达呈正相关(P<0.05)。结论高水平血浆APOE是PTC发生LNM的重要标志物,且与免疫细胞浸润相关,其可作为评估PTC发生及进展的新型生物标志物。

Objective Explore the role of APOE in the occurrence of PTC and lymph node metastasis(LNM).Methods A retrospective analysis was conducted among 161 patients with PTC(PTC group)who were pathologically confirmed after surgery in the Department of Otolaryngology,Head and Neck Surgery,First Affiliated Hospital of Hebei North University from September 2019 to September 2022,and 31 patients with nodular goiter(control group).PTC patients were divided into LNM group(51 cases)and pure PTC group(patients without LNM,110 cases).According to the median level of APOE,the PTC group was divided into high level group(>128.90 ng/L,n=80)and low level group(≤128.90 ng/L,n=81).Measure the plasma APOE concentrationnof patients through enzyme⁃linked immunosorbent assay(ELISA).Multivariate logistic regression was used to analyze the relationship between the baseline data,lipid metabolism related indicators and APOE protein level and PTC and LNM between the two groups. The ROC curve was drawn to evaluatethe predictive value of APOE on the occurrence of PTC. TIMER database was used to analyze the difference expression of APOE genebetween pan⁃cancer and normal tissues adjacent to cancer, and the correlation between the expression of APOE protein in thyroid carci⁃noma and the infiltration of immune cells. Results The level of APOE in PTC group was significantly higher than that in the controlgroup (P<0.05), while HDL⁃C and APOA1 were lower than that in the control group (P<0.05). Multivariate Logistic analysis showedthat APOE was an independent risk factor for predicting the occurrence and development of PTC (P = 0.022). The AUC of APOE topredict the occurrence of PTC was 0.639,the diagnostic cutoff value was 109.99 ng/ L, the sensitivity was 81.4%, and the specificitywas 48.4%. The APOE level in the LNM group was significantly higher than that in the pure PTC group ( P = 0.022 ). APOE, age,LP (a) were significantly associated with LNM in PTC (P<0.05). The more the number of lymph nodes, the higher level of APOE(OR=1.286, 95%CI:1.033~1.602, P<0.05). TIMER database analysis results show that APOE was higher expressed in thyroid car⁃cinoma than that of normal tissues adjacent to cancer (P<0.01). APOE was positively correlated with the expression of B cells, neutro⁃phils, CD8+T cells, CD4+T cells, macrophages and dendritic cells (P<0.05). Conclusion High level of plasma APOE are impor⁃tant markers for the occurrence and LNM of PTC, and is associated with immune cell infiltration. It can be used as a new biomarker toevaluate the occurrence and progression of PTC.