长程2型糖尿病对胰腺导管腺癌肿瘤相关巨噬细胞和预后的影响

Effect of long-term type 2 diabetes mellitus on tumor-associated macrophages and prognosis of pancreatic ductal adenocarcinoma

目的探讨病程较长(≥3年)的糖尿病是否影响胰腺癌中肿瘤相关巨噬细胞(TAMs)的极化,以及对胰腺癌患者预后的影响。方法收集2011年至2016年在武汉大学中南医院接受胰腺癌手术的患有长程2型糖尿病或无糖尿病患者的标本83例。采用免疫组织化学法分析组织切片中CD68和CD163的表达。运用Kaplan-Meier曲线和Log-rank检验分析生存曲线,Cox回归模型进行单因素和多因素分析。结果长程2型糖尿病(DM)组的CD68^(+)TAMs(P<0.05)、CD163^(+)TAMs(P<0.01)及CD163^(+)/CD68^(+)比例(P<0.01)均高于非糖尿病(NDM)组,差异有统计学意义。长程2型糖尿病与患者的组织分化程度、局部浸润和CA19-9的水平明显相关(P均<0.05)。长程2型糖尿病和CD163^(+)/CD68^(+)比例是无复发生存期(RFS)和总生存期(OS)的独立影响因素(P均<0.05),长程2型糖尿病明显缩短患者的RFS和OS。结论长程2型糖尿病与胰腺癌的恶性程度明显相关,并吸引更多的巨噬细胞聚集于肿瘤中,这些巨噬细胞同时大量极化为M2型TAMs。长程2型糖尿病和CD163^(+)/CD68^(+)比例是RFS和OS的独立影响因素。

Objective To study whether long-term diabetes(≥3 years)affects the polarization of tumor-associated macrophages(TAMs)in pancreatic ductal adenocarcinoma(PDAC)and its impact on the prognosis of patients with PDAC.Methods A total of 83 resected specimens of patients with long-term type 2 diabetes mellitus(T2DM)or without diabetes who underwent PDAC surgery in the hospital from 2011 to 2016 were collected.The expression of CD68 and CD163 in tissue sections were analyzed by immunohistochemistry.Kaplan-Meier curve with Log-rank test was used to analyze survival curves,and Cox proportional hazard model was used for univariate and multivariate analysis.Results CD68^(+)TAMs(P<0.05),CD163^(+)TAMs(P<0.01)and CD163^(+)/CD68^(+)ratio(P<0.01)in the long-term T2DM(DM)group were higher than those in non-T2DM(NDM)group,there were statistically significant differences.Long-term T2DM was associated with poor differentiation,local infiltration and CA19-9 level(all P<0.05).Long-term T2DM and CD163^(+)/CD68^(+)ratio were independent factors of recurrence-free survival(RFS)and overall survival(OS)(both P<0.05).Long-term T2DM could significantly shorten RFS and OS of patients.Conclusion Long-term T2DM was associated with malignant level of PDAC,and attracted more macrophages to accumulate in the tumor,and most of those were simultaneously transformed into M2-like TAMs.Long-term T2DM and CD163^(+)/CD68^(+)ratio were independent factors of RFS and OS.