基于单细胞RNA测序和免疫组织化学分析的补体C1QC作为结肠癌潜在预后标志物和治疗靶点

IF 3.1 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Huiming Deng, Yan Chen, Yong Liu, Li Liu, Ronghua Xu
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引用次数: 8

摘要

免疫细胞浸润在结肠癌的发生发展中起着至关重要的作用。然而,结肠癌中主要的肿瘤相关免疫细胞浸润及其基因调控仍需进一步明确,为该病的诊断和治疗提供新的视角。本研究首先从GEO数据库获取单细胞RNA测序(scRNA-seq)表达谱和TCGA结肠癌数据集。然后,采用Seurat、Monocle、LIMMA、Clusterprofile、GSVA和GSEABase算法对数据进行系统检验。在Drugbank数据库中分析靶基因对应的潜在靶药物,并通过分子对接检测。免疫组织化学检测组织芯片中C1QC的表达水平。单细胞分析提示中性粒细胞活化可能是结肠癌的关键调控途径,巨噬细胞是主要参与的细胞群。随后对巨噬细胞中差异基因的功能富集分析表明,C1QC可能是结肠癌发生发展的关键调控因子,与患者的生存密切相关。根据药物靶标预测,palivizumab是C1QC的靶向药物,分子对接证实palivizumab与C1QC结合。此外,基于组织微阵列的免疫组化分析显示,C1QC在结肠癌组织中高表达,且C1QC高表达的结肠癌患者预后较差,与年龄、淋巴转移及TNM分期(Tumor, Nodes and Metastases)密切相关。我们的研究结果提示,C1QC可能调控巨噬细胞在结肠癌免疫浸润中的作用,有望成为结肠癌潜在的免疫治疗靶点,有利于结肠癌患者的诊断和预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Complement C1QC as a potential prognostic marker and therapeutic target in colon carcinoma based on single-cell RNA sequencing and immunohistochemical analysis.

Complement C1QC as a potential prognostic marker and therapeutic target in colon carcinoma based on single-cell RNA sequencing and immunohistochemical analysis.

Complement C1QC as a potential prognostic marker and therapeutic target in colon carcinoma based on single-cell RNA sequencing and immunohistochemical analysis.

Complement C1QC as a potential prognostic marker and therapeutic target in colon carcinoma based on single-cell RNA sequencing and immunohistochemical analysis.

Immune cell infiltration plays an essential role in the occurrence and development of colon cancer. However, the main tumor-associated immune cell infiltration and its gene regulation in colon cancer still need to be further clarified in order to provide a new perspective for diagnosing and treating this disease. For this study, single-cell RNA sequencing (scRNA-seq) expression profiles and TCGA colon cancer data sets were first acquired from the GEO database. Then, Seurat, Monocle, LIMMA, Clusterprofile, GSVA and GSEABase algorithms were used to systematically examine the data. Potential target drugs corresponding to target genes were analyzed in the Drugbank database and detected by molecular docking. Immunohistochemistry was used to assess the level of C1QC expression in the tissue microarray. Single cell analysis suggested that neutrophil activation might be the critical regulatory pathway in colon cancer and that macrophages were the main cell population involved. Subsequent functional enrichment analysis on differential genes in macrophages suggested that C1QC may be a critical regulatory factor in the occurrence and progression of colon cancer, and was closely related to the survival of patients. According to the drug target prediction, palivizumab is a targeted drug for C1QC, and molecular docking demonstrated that palivizumab binds to C1QC. Additionally, tissue-microarray based immunohistochemical analysis showed that C1QC was highly expressed in colon cancer tissue, and the prognosis of colon cancer patients with high C1QC expression was worse, closely related to age, lymphatic metastasis and the TNM stage (Tumor, Nodes and Metastases). Our findings suggest that C1QC may regulate the macrophages in colon cancer immune infiltration, which is expected to be a potential immunotherapy target for colon cancer, and beneficial for the diagnosis and prognosis of colon cancer patients.

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来源期刊
Bosnian journal of basic medical sciences
Bosnian journal of basic medical sciences 医学-医学:研究与实验
CiteScore
7.40
自引率
5.90%
发文量
98
审稿时长
35 days
期刊介绍: The Bosnian Journal of Basic Medical Sciences (BJBMS) is an international, English-language, peer reviewed journal, publishing original articles from different disciplines of basic medical sciences. BJBMS welcomes original research and comprehensive reviews as well as short research communications in the field of biochemistry, genetics, immunology, microbiology, pathology, pharmacology, pharmaceutical sciences and physiology.
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