Abstract
BackgroundImmunotherapies 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.MethodsWe 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.ResultsWe 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.ConclusionOverall, 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.
Highlights
According to the latest estimates of the global cancer burden released by the International Agency for Research on Cancer (IARC) in 2020, colorectal cancer (CRC) is the third most common cancer globally, with the second highest case fatality rate
Through correlation analysis and strength analysis of the ligand-receptor interaction (LRI), we found that through ICAM1:IL2RA, the specific interaction among mDCs, DCregs and regulatory T cells affects the infiltration of Dendritic cell (DC) in CRC tissues
Through the analysis of the influencing factors of tumorinfiltrating lymphocytes (TILs), we revealed that the infiltration of monocytes in CRC tissues was significantly affected by LRIs
Summary
According to the latest estimates of the global cancer burden released by the International Agency for Research on Cancer (IARC) in 2020, colorectal cancer (CRC) is the third most common cancer globally, with the second highest case fatality rate. As an essential component of cell–cell communication, LRIs play a vital role in the development and treatment of cancer. LRIs involve various cells in the tumor microenvironment, and interactions in different cells produce different effects. Current research is mainly limited to the impact of a single ligand-receptor pair between two cell. With the widespread use of single-cell RNA sequencing (scRNA-seq), several studies have developed algorithms and tools to investigate the effects of LRIs via scRNA-seq data [2, 3], which makes it possible to explore LRIs in a holistic way. Immunotherapies targeting ligand-receptor interactions (LRIs) are advancing rapidly in the treatment of colorectal cancer (CRC), and LRIs affect many aspects of CRC development. The pattern of LRIs in CRC and their effect on tumor microenvironment and clinical value are still unclear
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