Delineation of colorectal cancer ligand-receptor interactions and their roles in the tumor microenvironment and prognosis

Lin, Hui; Xia, Lu; Lian, Jiabian; Chen, Yinan; Zhang, Yiyi; Zehao, Zhuang; Cai, Huajun; You, Jun; Guan, Guoxian

doi:10.1186/s12967-021-03162-0

Cited by 11 publications

(12 citation statements)

References 58 publications

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“…For instance, one study analyzed scRNA-seq and TCGA RNA-seq data of glioma cells and showed that ligands and receptors notably affect prognostic outcomes ( Yuan et al, 2019 ). Similarly, the research identified colorectal cancer subtypes based on ligand-receptor pairs (LR pairs), indicating that LR pairs are also associated with colorectal cancer immunotherapy response and prognosis ( Lin et al, 2021 ). Lung adenocarcinoma can also find Ligand-receptor interaction atlas within and between tumor cells and T cells ( Chen et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Studies have revealed that ligands-receptor pairs affect subtypes and the prognostic outcomes in different kinds of cancers such as glioma ( Yuan et al, 2019 ), colorectal cancer ( Lin et al, 2021 ), Lung adenocarcinoma ( Chen et al, 2020 ), and triple-negative breast cancer ( Pan et al, 2022 ). However, previous LR pairs study in melanoma was limited.…”

Section: Introductionmentioning

confidence: 99%

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Melanoma molecular subtyping and scoring model construction based on ligand-receptor pairs

Lin

Sun

et al. 2023

Front. Genet.

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Melanoma is a malignancy of melanocytes, responsible for a high percentage of skin cancer mortality. Ligand-Receptor pairs, a type of cellular communication, are essential for tumor genesis, growth, metastasis, and prognosis. Yet, the role of Ligand-Receptor pairs in melanoma has not been fully elucidated. Our research focused on the function of Ligand-Receptor pairs in melanoma prognosis. We screened 131 melanoma prognosis corresponded ligand-receptor pairs by analyzing the TCGA data of melanoma and the 2293 LR pairs retrieved from the connectomeDB2020 database. And further developed subtypes of melanoma according to the expression of these ligand-receptor pairs by Consensus Clustering. Then we using lasso cox regression and stepwise multivariate regression analysis established a ligand-receptor pairs-based scoring model for the evaluation of melanoma prognosis. Our study demonstrated that the ligand-receptor pairs are vital to the molecular heterogeneity of melanoma, and characterized three different melanoma ligand-receptor pairs subtypes. Among them, the C3 subtype showed a better prognosis, while the C1 subtype exhibited a low prognosis state. And our analysis then found out that this could be related to the differed activation and inhabitation of the cell cycle and immune-related pathways. Using lasso cox regression and stepwise multivariate regression analysis, we further identified 9 key ligand-receptor pairs and established a scoring model that effectively correlated with the prognosis, immune pathways, and therapy of melanoma, showing that the LR.score model was a trustworthy and independent biomarker for melanoma prognosis evaluation. In sum, we found that ligand-receptor pairs are significantly associated with the prognosis and therapy of melanoma. And our ligand-receptor-based scoring model showed potential for the evaluation of melanoma prognosis and immune therapy outcome prediction, which is crucial to the survival for the patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Melanoma molecular subtyping and scoring model construction based on ligand-receptor pairs

Lin

Sun

et al. 2023

Front. Genet.

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“…Therefore, it is imperative to explore a novel taxonomy to stratify stage II/III CRC patients well and determine who may truly demand or can omit ACT. Serving as the instrumental basis for the communication of cells with neighboring cells and the whole organism, LRIs exert widely divergent implications on CRC in many dimensions from the viewpoint of intercellular crosstalk 16,27,33 . Our study deciphered the heterogeneity of stage II/III CRC from the abnormal crosstalk of ligand-receptor gene pairs and proposed a promising subtyping scheme based on perturbations in LRIs.…”

Section: Discussionmentioning

confidence: 99%

Perturbations in the ligand-receptor interactions unravel novel heterogeneous subtypes of stage II/III colorectal cancer

Han

Xu²,

Chen³

et al. 2023

Preprint

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Approximately 10%-15% of stage II and 25%-30% of stage III colorectal cancer (CRC) patients experience recurrence within five years after surgery, while existing taxonomies are inadequate for daily clinical application. Therefore, a more reliable classification approach with higher accuracy and prognostic potential is urgently required to stratify stage II/III CRC and identify potential patients who will benefit from postoperative adjuvant therapy. Alternatively, interactions of ligand-receptor pairs point to an emerging direction in tumor signaling with far-reaching implications for CRC, while their impact on tumor subtyping has not been elucidated. Herein, 304 normal samples, 1,386 stage II/III CRC patients, and 2,557 ligand-receptor pairs were retrospectively retrieved. Grounded on perturbations in ligand-receptor interactions, four well-characterized and robust ligand-receptor-driven subtypes (LRDS1-4) were established in the discovery cohort and validated in meta-GEO cohort comprising nine independent cohorts. Specifically, LRDS1 was characterized by an immune-cold phenotype, with cell proliferation and differentiation-related functions and higher tumor purity; LRDS2 was endowed with matrix activation-related pathways and sensitive to fluorouracil-based chemotherapy; LRDS3 was distinguished by elevated metabolic activities and frequent 13q12.2 amplification; LRDS4 was an immune-hot subtype, driven by mutations, and exhibiting dismal prognosis with MEIS2 as the prognostic feature gene. Overall, our study developed four heterogeneous LRDS and shed novel insights into the implications of intercellular communication on stage II/III CRC from a ligand-receptor interactome perspective.

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“…In the progression of cancer, cancer cell-stromal cell crosstalk is orchestrated by a plethora of ligand-receptor interactions to generate a TME that favors tumor growth ( 18 ). Intercellular communication through LR pairs in the tumor microenvironment underlie the poor prognosis of multiple cancers, such as pancreatic ductal adenocarcinoma ( 19 ) and colorectal cancer ( 20 ). Increasing discoveries of receptors and ligands and their interactions has encouraged the integration of the available information on ligand-receptor interactions from many databases to facilitate research ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

The molecular subtypes of triple negative breast cancer were defined and a ligand-receptor pair score model was constructed by comprehensive analysis of ligand-receptor pairs

et al. 2022

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BackgroundIntercellular communication mediated by ligand-receptor interactions in tumor microenvironment (TME) has a profound impact on tumor progression. This study aimed to explore the molecular subtypes mediated by ligand-receptor (LR) pairs in triple negative breast cancer (TNBC), identify the most important LR pairs to construct a prognostic risk model, and study their effect on TNBC immunotherapy.MethodsLR pairs subclasses of TNBC were categorized by consensus clustering based on LR Pairs in METABRIC dataset. Least absolute shrinkage and selection operator (LASSO) Cox regression and stepwise Akaike information criterion (stepAIC) were conducted to build a LR pairs score model. The relationship between LR pairs score and immune cell infiltration, stromal score and immune score associated with TME was analyzed, and the prediction of drug therapy and immunotherapy efficacy by LR pairs score was evaluated.ResultsAccording to the expression pattern of 145 TNBC prognostic LR pairs, the samples were divided into three subclasses with different survival outcomes, copy number variation (CNV), TME immune cell infiltration, stromal score and immune score. The LR pairs score model constructed in the METABRIC dataset was composed of four LR pairs, and its predictive significance for TNBC prognosis was verified in GSE58812 and GSE21653 cohorts. In addition, LR pairs score was negatively correlated with several immune pathways regulating immunity and immune score, and related to the sensitivity of anti-neoplastic drugs and the effect of anti-PD-L1 therapy.ConclusionOur study confirmed the impact of LR pairs on the molecular heterogeneity of TNBC, characterized three LR pairs subtypes with different survival outcomes and TME patterns, and proposed a LR pairs score system with predictive significance for TNBC prognosis and anti-PD-L1 therapeutic effect, which provides a potential evaluation scheme for TNBC management.

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Delineation of colorectal cancer ligand-receptor interactions and their roles in the tumor microenvironment and prognosis

Cited by 11 publications

References 58 publications

Melanoma molecular subtyping and scoring model construction based on ligand-receptor pairs

Melanoma molecular subtyping and scoring model construction based on ligand-receptor pairs

Perturbations in the ligand-receptor interactions unravel novel heterogeneous subtypes of stage II/III colorectal cancer

The molecular subtypes of triple negative breast cancer were defined and a ligand-receptor pair score model was constructed by comprehensive analysis of ligand-receptor pairs

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