巨噬细胞浸润的胰腺癌患者预后分析及特征基因初筛

Prognostic analysis of macrophage infiltration in patients with pancreatic cancer and preliminary screening of differential genes

目的分析巨噬细胞浸润与胰腺癌患者预后的相关性,并通过生物信息学分析胰腺癌患者M2型巨噬细胞浸润的相关基因。方法选择2015年6月至2018年12月兰州大学第一医院收治的32例胰腺癌患者为研究对象,其中男性19例,女性13例,年龄(61.8±2.8)岁。收集患者癌组织和癌旁组织,以及相关临床资料,包括:血清糖类抗原19-9、肿瘤TNM分期、血管侵犯等。对样本行F4/80(巨噬细胞标志物)免疫组化染色。随访生存时间,并分析其与上述指标的相关性。使用癌症基因组图谱(TCGA)数据库胰腺癌数据行生物信息学分析。结果胰腺癌患者生存时间与癌组织巨噬细胞的浸润程度负相关(r=-0.522,P=0.002),与癌旁组织未见明显关系(r=0.168,P=0.358)。癌组织巨噬细胞浸润程度联合术前血清糖类抗原19-9、肿瘤TNM分期、血管侵犯对胰腺癌患者生存时间的解释度达到47.4%(R^(2)=0.474)。TCGA数据库等进行生物信息学分析得到胰腺癌中95个差异基因与M2型巨噬细胞浸润显著相关,其中主要为基因JPH3(正相关)和IL17REL(负相关)。结论癌组织巨噬细胞浸润程度可以作为胰腺癌患者预后预测因素,联合术前血清糖类抗原19-9、肿瘤TNM分期、血管侵犯预测预后更为准确。M2型巨噬细胞浸润的相关机制研究可以围绕JPH3和IL17REL等差异基因展开。

Objective To analyze the correlations between the prognosis of patients with pancreatic cancer and macrophage infiltration,and to find the differential gene correlated with macrophage infiltration in patients with pancreatic cancer through bioinformatics.Methods A total of 32 patients with pancreatic cancer admitted to the First Hospital of Lanzhou University from June 2015 to December 2018 were selected as the research objects,including 19 males and 13 females,with the age of(61.8±2.8)years.Cancer tissues,adjacent tissues,and related clinical data were collected.F4/80(macrophage marker)immunohistochemical staining was performed on the samples.The survival time was followed up and its correlation with the above indexes was analyzed.The pancreatic cancer data from The Cancer Genome Atlas(TCGA)database was used for bioinformatics analysis.Results The survival time of pancreatic cancer patients was negatively correlated with degree of macrophage infiltration in cancer tissues(r=-0.522,P=0.002),but not with adjacent tissues(r=0.168,P=0.358).The degree of macrophage infiltration in cancer tissue combined with preoperative serum carbohydrate antigen 19-9(CA19-9),tumor TNM stage and vascular invasion can predict survival up to 47.4%of the survival time(R^(2)=0.474).TCGA database bioinformatic analysis showed that in pancreatic cancer there were 95 differentially expressed genes significantly correlated with M2 macrophage infiltration,among which JPH3(positive correlation)and IL17REL(negative correlation)were the main genes.Conclusion The degree of macrophage infiltration in cancer tissue can be used as a prognostic factor for patients with pancreatic cancer,and the combination with preoperative serum CA19-9,tumor TNM stage and vascular invasion is more accurate in predicting the prognosis.The related mechanism of M2 macrophage infiltration can be studied around the differential genes such as JPH3 and IL17REL.