空间异质性和细胞溶酶体通路的免疫浸润显示了食管癌肿瘤异质性的新蓝图。
Spatial heterogeneity and Immune infiltration of cellular lysosomal pathways reveals a new blueprint for tumor heterogeneity in esophageal cancer.
发表日期:2023
作者:
Jinxing Wei, XiaoMing Wu, Shuohao Wang, Siqing Liu, Xia Gao
来源:
Frontiers in Endocrinology
摘要:
食管鳞状细胞癌(ESCC)是消化道常见恶性肿瘤,可能与溶酶体途径有关。本研究旨在探讨溶酶体途径与ESCC免疫浸润之间的相关性。通过单细胞数据进行ESCC患者的细胞类型注释和其基因标记的分布分析。根据溶酶体途径的表达分组,进行基因集变异分析(GSVA)富集途径评分,使用Cellchat细胞通信对不同细胞群体的肿瘤相关途径评分和相互作用进行分析。使用算法筛选相关差异基因,构建预后风险标记,并直接评估溶酶体途径相关的基因风险评分与免疫浸润和肿瘤治疗药物敏感性之间的关联。在细胞实验中,采用qPCR和流式细胞术评估溶酶体途径基因MT1X在肿瘤细胞发展中的作用。通过t-sne降维分析,将ESCC单细胞数据注释为7个聚类簇。Cellchat分析显示,“MIF”细胞通信网络是ESCC细胞中溶酶体途径的主要通信模式。在训练和验证组中发现,溶酶体途径遗传风险模型与ESCC预后显著不同。使用oncopredict R包,发现溶酶体途径基因风险模型与ESCC患者的治疗耐药有关。使用MCPcounter方法评估了溶酶体差异表达基因的表达与肿瘤免疫浸润和免疫细胞类型之间的相关性。细胞实验显示,溶酶体途径基因MT1X在食管癌细胞中的表达量低于正常食管上皮细胞。MT1X的敲除显著促进了食管癌细胞的生长速度。基于单细胞测序技术和转录组分析,我们确认了ESCC的溶酶体途径与免疫浸润和治疗敏感性之间的密切关联,这可能是ESCC疗法新方向的潜在靶标。版权所有©2023 Wei,Wu,Wang,Liu和Gao。
Esophageal squamous cell carcinoma (ESCC) is a common Malignant tumor of digestive tract which have a potential association with lysosomal pathway. The purpose of this study was to explore the correlation between lysosome pathway and immune infiltration of ESCC.The cell type annotation of ESCC patients and the distribution of their gene markers were analyzed by single cell data. They were also grouped according to the expression of lysosomal pathways. Gene set variation analysis (GSVA) enriched pathway scoring, Cellchat cell communication was performed to demonstrate the tumour-associated pathway scores and interactions of different cell populations. Relevant differential genes were screened, prognostic risk markers were constructed and direct associations of lysosomal pathway-related gene risk scores with immune infiltration and tumour treatment drug sensitivity were assessed by algorithms. In cellular experiments, qPCR and flow cytometry were used to assess the role of the lysosomal pathway gene-MT1X on tumour cell development.ESCC single cell data were annotated into 7 Cluster clusters by t-sne downscaling analysis. Cellchat analysis revealed that the "MIF" cellular communication network is the main communication mode of the lysosomal pathway in ESCC cells. The lysosomal pathway genetic risk model was found to be significantly different from ESCC prognosis in both the training and validation groups. The lysosome pathway gene risk model was associated with treatment resistance in ESCC patients using oncopredict R package. The correlation between the expression of lysosomal-DEG and tumour immune infiltration and immune cell types by the MCPcounter method. Cellular assays showed that the lysosomal pathway gene MT1X was less expressed in oesophageal cancer cells than in normal oesophageal epithelial cells. Knockdown of MT1X significantly promoted the growth rate of oesophageal cancer cells.Based on the single cell sequencing technology and transcriptomic analysis, we confirmed that there is a close association between the lysosomal pathway and the immune infiltration and treatment sensitivity of ESCC, which may be a potential target for a new direction of ESCC therapy.Copyright © 2023 Wei, Wu, Wang, Liu and Gao.