OSCAR facilitates malignancy with enhanced metastasis correlating to inhibitory immune microenvironment in multiple cancer types

Liao, Xia; Yang, Baofeng; Zhang, Yaoyao; Xu, Binghui; Liang, Junrong; Jia, Qingan; Zhang, Chun

doi:10.7150/jca.51964

Cited by 3 publications

(3 citation statements)

References 30 publications

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“…The area under the curve (AUC) values for the receiver operating curve (ROC) were calculated and plotted using the “pROC” package and “ggplot2” package in R version 3.6.3. Survival data, made available from ICGC Data and TCGA portals, were analyzed with survival and “survminer” R packages [ 30 ]⁠, and validated by the Kaplan Meier plotter [ 31 ] with the median of SNX7 expression as the optimal cutoff point.…”

Section: Methodsmentioning

confidence: 99%

Comprehensive analysis and validation of SNX7 as a novel biomarker for the diagnosis, prognosis, and prediction of chemotherapy and immunotherapy response in hepatocellular carcinoma

Chen,

Gao,

Zhang

et al. 2023

BMC Cancer

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Background Studies have demonstrated that Sorting nexin 7 (SNX7) functions as an anti-apoptotic protein in liver tissue and plays a crucial role in the survival of hepatocytes during early embryonic development. However, its diagnostic and prognostic value as well as the predictive value of chemotherapy and immunotherapy have not been reported in hepatocellular carcinoma (HCC). Methods SNX7 mRNA expression and its diagnostic efficacy were examined in GEO datasets, and the findings were further confirmed in TCGA, ICGC cohorts, and cell lines. The protein level of SNX7 was determined using CPTAC and HPA databases, and the results were validated through immunohistochemistry (IHC). Survival analyses were performed in TCGA and ICGC cohorts, and the results were subsequently validated via Kaplan–Meier Plotter. The response to chemotherapy and immunotherapy was predicted via GDSC dataset and TIDE algorithm, respectively. R packages were employed to explore the relationship between SNX7 expression and immune infiltration, m6A modification, as well as the functional enrichment of differentially expressed genes (DEGs). Results The expression of SNX7 at both mRNA and protein levels was significantly upregulated in HCC tissues. SNX7 exhibited superior diagnostic efficacy compared to AFP alone for HCC detection, and combining it with AFP improved the diagnostic accuracy for HCC. High SNX7 was associated with unfavorable outcomes, including poor overall survival, disease-specific survival, progression-free survival, and advanced pathological stage, in patients with HCC, and SNX7 was identified as an independent risk factor for HCC. Moreover, elevated SNX7 expression was positively correlated with increased sensitivity to various chemotherapy drugs, including sorafenib, while it was associated with resistance to immunotherapy in HCC patients. Correlation analysis revealed a relationship between SNX7 and multiple m6A-related genes and various immune cells. Finally, enrichment analysis demonstrated strong associations of SNX7 with critical biological processes, such as cell cycle regulation, cellular senescence, cell adhesion, DNA replication, and mismatch repair pathway in HCC. Conclusions Our study highlights the association of SNX7 with the immune microenvironment and its potential influence on HCC progression. SNX7 emerges as a promising novel biomarker for the diagnosis, prognosis, and prediction of response to chemotherapy and immunotherapy in patients with HCC.

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Section: Methodsmentioning

confidence: 99%

Comprehensive analysis and validation of SNX7 as a novel biomarker for the diagnosis, prognosis, and prediction of chemotherapy and immunotherapy response in hepatocellular carcinoma

Chen,

Gao,

Zhang

et al. 2023

BMC Cancer

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“…The Osteoclast-associated receptor (OSCAR) is a collagen receptor in the same family as LAIR-1, but with stimulatory signaling capacity through cytoplasmic association with FcRγ, which contains an Immunoreceptor Tyrosine-based Activation Motif (ITAM) ( 85 , 86 ). OSCAR is expressed not only on osteoclasts, but also on other myeloid cell subsets, and OSCAR RNA is overexpressed in several cancers ( 87 ). Interestingly, despite OSCAR’s stimulatory capacity, RNA expression appears to positively associate with M2 macrophage differentiation, T cell exhaustion, cancer progression and metastasis, although much remains to be learned in the context of cancer.…”

Section: Tumor Ecm Ligands Interact With Immune Cell Receptorsmentioning

confidence: 99%

Regulation of tumor immunity and immunotherapy by the tumor collagen extracellular matrix

Flies,

Langermann,

Jensen

et al. 2023

Front. Immunol.

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It has been known for decades that the tumor extracellular matrix (ECM) is dysfunctional leading to loss of tissue architecture and promotion of tumor growth. The altered ECM and tumor fibrogenesis leads to tissue stiffness that act as a physical barrier to immune cell infiltration into the tumor microenvironment (TME). It is becoming increasingly clear that the ECM plays important roles in tumor immune responses. A growing body of data now indicates that ECM components also play a more active role in immune regulation when dysregulated ECM components act as ligands to interact with receptors on immune cells to inhibit immune cell subpopulations in the TME. In addition, immunotherapies such as checkpoint inhibitors that are approved to treat cancer are often hindered by ECM changes. In this review we highlight the ways by which ECM alterations affect and regulate immunity in cancer. More specifically, how collagens and major ECM components, suppress immunity in the complex TME. Finally, we will review how our increased understanding of immune and immunotherapy regulation by the ECM is leading towards novel disruptive strategies to overcome immune suppression.

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“…It was found that OSCAR may interact with fibrillar collagens released in the extracellular matrix (ECM) from bone surfaces, where OCPs undergo maturation and terminal differentiation in vivo [ 5 ]. It is also known that OSCAR-collagen interactions play an important role during bone development, maintenance, repair, and disease [ 7 , 9 , 10 , 11 ]. For this reason, different research groups have tried to elucidate the OSCAR-collagen interaction, with particular attention to its capability to promote OC differentiation and osteoclastogenesis as well as mature OC activation [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Collagen-like Osteoclast-Associated Receptor (OSCAR)-Binding Motifs Show a Co-Stimulatory Effect on Osteoclastogenesis in a Peptide Hydrogel System

Vitale,

Ligorio,

Richardson

et al. 2023

IJMS

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Osteoclastogenesis, one of the dynamic pathways underlying bone remodelling, is a complex process that includes many stages. This complexity, while offering a wealth of therapeutic opportunities, represents a substantial challenge in unravelling the underlying mechanisms. As such, there is a high demand for robust model systems to understand osteoclastogenesis. Hydrogels seeded with osteoclast precursors and decorated with peptides or proteins mimicking bone’s extracellular matrix could provide a useful synthetic tool to study pre-osteoclast-matrix interactions and their effect on osteoclastogenesis. For instance, fibrillar collagens have been shown to provide a co-stimulatory pathway for osteoclastogenesis through interaction with the osteoclast-associated receptor (OSCAR), a regulator of osteoclastogenesis expressed on the surface of pre-osteoclast cells. Based on this rationale, here we design two OSCAR-binding peptides and one recombinant OSCAR-binding protein, and we combine them with peptide-based hydrogels to study their effect on osteoclastogenesis. The OSCAR-binding peptides adopt the collagen triple-helical conformation and interact with OSCAR, as shown by circular dichroism spectropolarimetry and surface plasmon resonance. Furthermore, they have a positive effect on osteoclastogenesis, as demonstrated by appropriate gene expression and tartrate-resistant acid phosphatase staining typical of osteoclast formation. Combination of the OSCAR-binding peptides or the OSCAR-binding recombinant protein with peptide-based hydrogels enhances osteoclast differentiation when compared to the non-modified hydrogels, as demonstrated by multi-nucleation and by F-actin staining showing a characteristic osteoclast-like morphology. We envisage that these hydrogels could be used as a platform to study osteoclastogenesis and, in particular, to investigate the effect of costimulatory pathways involving OSCAR.

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OSCAR facilitates malignancy with enhanced metastasis correlating to inhibitory immune microenvironment in multiple cancer types

Cited by 3 publications

References 30 publications

Comprehensive analysis and validation of SNX7 as a novel biomarker for the diagnosis, prognosis, and prediction of chemotherapy and immunotherapy response in hepatocellular carcinoma

Comprehensive analysis and validation of SNX7 as a novel biomarker for the diagnosis, prognosis, and prediction of chemotherapy and immunotherapy response in hepatocellular carcinoma

Regulation of tumor immunity and immunotherapy by the tumor collagen extracellular matrix

Collagen-like Osteoclast-Associated Receptor (OSCAR)-Binding Motifs Show a Co-Stimulatory Effect on Osteoclastogenesis in a Peptide Hydrogel System

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