Siglec-15是食管癌免疫治疗的一种新的潜在靶点

Siglec-15 is a novel immunotherapy target for esophageal cancer patients

目的明确食管癌组织中Siglec-15表达与免疫细胞浸润及PD-L1表达的关系,评估Siglec-15作为食管癌免疫治疗新靶点的价值。方法使用癌症基因组图谱(TCGA)、产生有效治疗的应用研究(TARGET)和基因型-组织表达(GTEx)数据库,通过Pearson相关性分析明确Siglec-15转录水平与食管癌免疫细胞浸润、肿瘤突变负荷水平、微卫星不稳定性状态和免疫检查点基因表达之间的相关性。收集129例临床食管癌肿瘤组织样本,免疫组织化学染色法检测食管癌组织中PD-L1及Siglec-15表达,根据PD-L1染色的综合阳性分数(CPS)分为高PD-L1组与低PD-L1组,采用t检验比较Siglec-15在高PD-L1组与低PD-L1组肿瘤组织中的表达差异。结果Siglec-15在食管癌等22种癌症的肿瘤组织中高表达(P<0.05)。食管癌组织中Siglec-15表达与免疫细胞浸润显著相关,Siglec-15高表达的肿瘤组织中CD4^(+)T细胞及CD8^(+)T细胞浸润减少(P<0.05)。Siglec-15表达水平与3种癌症(肉瘤、子宫内膜癌和卵巢浆液性囊腺癌)的突变负荷正相关(P<0.05),与5种癌症(脑胶质瘤、乳腺浸润癌、前列腺癌、头颈鳞状细胞癌和睾丸癌)的微卫星不稳定状态负相关(P<0.05)。临床食管癌样本检测显示,PD-L1低表达组肿瘤组织中Siglec-15表达水平明显高于PD-L1高表达组(P<0.05)。结论Siglec-15表达与食管癌组织中免疫细胞浸润及PD-L1表达相关,Siglec-15是食管癌免疫治疗的一种新的潜在靶点。

Objective To evaluate the value of Siglec-15 as a new target for the immunotherapy of patients with esophageal cancer.Methods Pan-cancer data were downloaded from TCGA,TARGET and GTEx databases.Pearson correlation analysis was used to analyze the correlation between Siglec-15 expression level and immune cell infiltration,tumor mutation burden(TMB),microsatellite instability(MSI)and immune checkpoint genes.Immunohistochemistry staining was used to detect the expression of PD-L1 and Siglec-15 protein in 129 cases of esophageal cancer tissue.Patients with esophageal cancer were divided into high PD-L1 group and low PD-L1 group according to the composite positive score(CPS)of PD-L1 staining.The expression of Siglec-15 was compared by t-test between high PD-L1 group and low PD-L1 group.Results Siglec-15 was highly expressed in 22 kinds of cancer tissues such as esophageal cancer etc(P<0.05).Siglec-15 expression in esophageal cancer was significantly correlated with immune cell invasion(P<0.05).The infiltration of CD4^(+)T cells and CD8^(+)T cells was reduced in tumour tissues with high Siglec-15 expression(P<0.05).The expression level of Siglec-15 was positively correlated with the TMB of three cancers(sarcoma,endometrioid cancer and ovarian serous cystadenocarcinoma;P<0.05)and negatively correlated with the MSI of five cancers(glioma,invasive breast cancer,prostate cancer,head and neck cancer and testicular cancer;P<0.05).Clinical esophageal cancer sample analysis showed that the expression of Siglec-15 was significantly higher in low PD-L1 group than in high PD-L1 group(P<0.05).Conclusion Siglec-15 expression is related to immune cell infiltration and PD-L1 expression in esophageal cancer tissue.Siglec-15 is a new potential target for immunotherapy in esophageal cancer patients.