Delineation of colorectal cancer ligand-receptor interactions and their roles in the tumor microenvironment and prognosis.
Delineation of colorectal cancer ligand-receptor interactions and their roles in the tumor microenvironment and prognosis.
复制标题
结直肠癌配体-受体相互作用及其在肿瘤微环境和预后中的作用的描述
DOI：
10.1186/s12967-021-03162-0
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发表时间：
2021-12-07
影响因子：
7.4
通讯作者：
Guan G
中科院分区：
文献类型：
--
作者：
Lin H;Xia L;Lian J;Chen Y;Zhang Y;Zhuang Z;Cai H;You J;Guan G
针对配体-受体相互作用(LRIS)的免疫治疗在结直肠癌(CRC)的治疗中正在迅速发展，LRIS也影响着结直肠癌发展的许多方面。然而，LRIS在结直肠癌中的模式及其对肿瘤微环境的影响和临床价值仍不清楚。我们在29例结直肠癌患者的55,539个单细胞RNA测序(scRNA-seq)样本和3个包含1411名结直肠癌患者数据的批量RNA-seq数据集中描绘了LRIS的模式。综合分析肿瘤微环境、免疫治疗对结直肠癌患者预后的影响。我们计算了25种细胞类型之间的1893个配体-受体对的强度，以重建结直肠癌的空间结构。我们基于LRIS确定了肿瘤亚型，揭示了亚型与免疫治疗疗效的关系，并探索了影响肿瘤浸润性淋巴细胞丰度的配体-受体对和特异性靶点。最后，构建了一个基于配体-受体对的预后模型，并进行了验证。总之，本研究通过对现有配体-受体对的全面深入研究，为结直肠癌亚型分类提供了新的思路，为结直肠癌患者提供了一种新的风险筛查工具，并为结直肠癌治疗提供了潜在的配体-受体对靶点和途径。网上版载有补充材料，可在10.1186/s12967-021-03162-0查阅。
Immunotherapies targeting ligand-receptor interactions (LRIs) are advancing rapidly in the treatment of colorectal cancer (CRC), and LRIs also affect many aspects of CRC development. However, the pattern of LRIs in CRC and their effect on tumor microenvironment and clinical value are still unclear. We delineated the pattern of LRIs in 55,539 single-cell RNA sequencing (scRNA-seq) samples from 29 patients with CRC and three bulk RNA-seq datasets containing data from 1411 CRC patients. Then the influence of tumor microenvironment, immunotherapy and prognosis of CRC patients were comprehensively investigated. We calculated the strength of 1893 ligand-receptor pairs between 25 cell types to reconstruct the spatial structure of CRC. We identified tumor subtypes based on LRIs, revealed the relationship between the subtypes and immunotherapy efficacy and explored the ligand-receptor pairs and specific targets affecting the abundance of tumor-infiltrating lymphocytes. Finally, a prognostic model based on ligand-receptor pairs was constructed and validated. Overall, through the comprehensive and in-depth investigation of the existing ligand-receptor pairs, this study provides new ideas for CRC subtype classification, a new risk screening tool for CRC patients, and potential ligand-receptor pair targets and pathways for CRC therapy. The online version contains supplementary material available at 10.1186/s12967-021-03162-0.