Targeting LAYN inhibits colorectal cancer metastasis and tumor-associated macrophage infiltration induced by hyaluronan oligosaccharides

Yang, Yabing; Chen, Zuyang; Chu, Xiaodong; Yan, Qiuxia; He, Jia-shuai; Guo, Yi; Zhao, Zhan; Zhang, Yiran; Hu, Dahai; Ding, Hui; Zhao, Xiaoxu; Pan, Yun-long; Dong, Hongmei; Wang, Lu; Pan, Jinghua

doi:10.1016/j.matbio.2023.02.005

“…LAYN is known to be one of the receptors for HA and involved in the reorganization of cytoskeleton structures [ 20 ]. The LAYN protein plays an important role in cell adhesion, migration, and cooperates with the body’s anti-tumor immunity [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…The LAYN protein plays an important role in cell adhesion, migration, and cooperates with the body’s anti-tumor immunity [ 21 ]. Previous studies have shown that LAYN was correlated with poor prognosis and tumor immune cell infiltration in colorectal cancer [ 20 ], gastric cancer [ 14 ], and hepatocellular carcinoma [ 21 ]. However, up to now, no studies have reported the expression and prognostic value of LAYN in HNSCC, and the association of LAYN with immune infiltration in HPV-positive and HPV-negative HNSCC.…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of LAYN in HPV-related head and neck squamous cell carcinoma and its influence on immune cell infiltration

Chen,

Lu

et al. 2024

Discov Onc

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Background HPV-positive head and neck squamous cell carcinoma (HNSCC) exhibits different characteristics from HPV-negative tumors in terms of tumor development, clinical features, treatment response, and prognosis. Layilin (LAYN), which contains homology with C-type lectins, plays a critical role in tumorigenesis and cancer progression. However, the prognostic value of LAYN and the relationship between LAYN and immune infiltration levels in HPV-related HNSCC patients still require a comprehensive understanding. Herein, we aimed to assess the prognostic value of LAYN and to investigate its underlying immunological function in HPV-related HNSCC. Methods Through various bioinformatics methods, we analyzed the data from The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to explore the potential underlying oncogenic impression of LAYN, including the relevance of LAYN to survival outcomes, clinicopathological factors, immune cell infiltration, and immune marker sets in HPV-related HNSCC. The expression levels of LAYN and HPV were also verified in HNSCC patient tissues. Results LAYN was differentially expressed in a variety of tumors. The expression of LAYN in HNSCC was significantly higher than that in adjacent normal tissues (P < 0.0001), and high expression of LAYN was correlated with poor overall survival (OS) in HNSCC patients (Hazard Ratio (HR) = 1.3, P = 0.035). Moreover, LAYN expression level in HPV-positive HNSCC patients was significantly lower than that in HPV-negative patients, with HPV-positive HNSCC patients displaying a trend of favorable prognosis. In addition, the relationship between LAYN expression and immune infiltration levels in HPV-positive HNSCC group was less tightly correlated than that in HPV-negative HNSCC group, and there was a strong relationship between LAYN expression and markers of M2 macrophage (P < 0.001) and exhausted T cells (P < 0.05) in HPV-negative HNSCC. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis suggested that LAYN potentially influenced tumor progression through HPV infection and other cancer-related pathways. Conclusions LAYN might contribute to tumorigenesis via its positive correlation with immune checkpoint molecules and tumor-associated macrophages (TAMs). Our study might provide a novel prognostic biomarker and latent therapeutic target for the treatment of HPV-related HNSCC.

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“…The LAYN protein plays an important role in cell adhesion, migration, and cooperates with the body's anti-tumor immunity [21]. Previous studies have shown that LAYN was correlated with poor prognosis and tumor immune cell in ltration in colorectal cancer [20], gastric cancer [14], and hepatocellular carcinoma [21]. However, up to now, no studies have reported the expression and prognostic value of LAYN in HNSCC, and the association of LAYN with immune in ltration in HPVpositive and HPV-negative HNSCC.…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Value of LAYN in HPV-related head and neck squamous cell carcinoma and its Influence on Immune Cell Infiltration

Chen,

Lu

et al. 2023

Preprint

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Background HPV-positive head and neck squamous cell carcinoma (HNSCC) exhibits different characteristics from HPV-negative tumors in terms of tumor development, clinical features, treatment response, and prognosis. Layilin (LAYN), which contains homology with C-type lectins, plays a critical role in tumorigenesis and cancer progression. However, the prognostic value of LAYN and the relationship between LAYN and immune infiltration levels in HPV-related HNSCC patients still require a comprehensive understanding. Herein, we aimed to assess the prognostic value of LAYN and to investigate its underlying immunological function in HPV-related HNSCC. Methods Through various bioinformatics methods, we analyzed the data from The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to explore the potential underlying oncogenic impression of LAYN, including the relevance of LAYN to survival outcomes, clinicopathological factors, immune cell infiltration, and immune marker sets in HPV-related HNSCC. The expression levels of LAYN and HPV were also verified in HNSCC patient tissues. Results LAYN was differentially expressed in a variety of tumors. The expression of LAYN in HNSCC was significantly higher than that in adjacent normal tissues (P < 0.0001), and high expression of LAYN was correlated with poor overall survival (OS) in HNSCC patients (Hazard Ratio (HR) = 1.3, P = 0.035). Moreover, LAYN expression level in HPV-positive HNSCC patients was significantly lower than that in HPV-negative patients, with HPV-positive HNSCC patients displaying a trend of favorable prognosis. In addition, the relationship between LAYN expression and immune infiltration levels in HPV-positive HNSCC group was less tightly correlated than that in HPV-negative HNSCC group, and there was a strong relationship between LAYN expression and markers of M2 macrophage (P < 0.001) and exhausted T cells (P < 0.05) in HPV-negative HNSCC. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis suggested that LAYN potentially influenced tumor progression through HPV infection and other cancer-related pathways. Conclusions LAYN might contribute to tumorigenesis via its positive correlation with immune checkpoint molecules and tumor-associated macrophages (TAMs). Our study might provide a novel prognostic biomarker and latent therapeutic target for the treatment of HPV-related HNSCC.

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“…The role of HA is complex: it potentially acts as both a physical barrier and a signaling molecule that influences the immune response. An HA-rich environment can also promote tumor-associated macrophage infiltration and differentiation into a pro-tumor phenotype ( Yang et al ., 2023 ). Patients with high HA levels had significantly shorter survival.…”

Section: Extracellular Matrix (Ecm) Proteinsmentioning

confidence: 99%

Tumor Stroma as a Therapeutic Target for Pancreatic Ductal Adenocarcinoma

Lee,

Han,

Jung

et al. 2024

Biomol Ther (Seoul)

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Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis owing to its desmoplastic stroma. Therefore, therapeutic strategies targeting this tumor stroma should be developed. In this study, we describe the heterogeneity of cancer-associated fibroblasts (CAFs) and their diverse roles in the progression, immune evasion, and resistance to treatment of PDAC. We subclassified the spatial distribution and functional activity of CAFs to highlight their effects on prognosis and drug delivery. Extracellular matrix components such as collagen and hyaluronan are described for their roles in tumor behavior and treatment outcomes, implying their potential as therapeutic targets. We also discussed the roles of extracellular matrix (ECM) including matrix metalloproteinases and tissue inhibitors in PDAC progression. Finally, we explored the role of the adaptive and innate immune systems in shaping the PDAC microenvironment and potential therapeutic strategies, with a focus on immune cell subsets, cytokines, and immunosuppressive mechanisms. These insights provide a comprehensive understanding of PDAC and pave the way for the development of prognostic markers and therapeutic interventions.

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Targeting LAYN inhibits colorectal cancer metastasis and tumor-associated macrophage infiltration induced by hyaluronan oligosaccharides

Cited by 7 publications

References 31 publications

The prognostic value of LAYN in HPV-related head and neck squamous cell carcinoma and its influence on immune cell infiltration

The prognostic value of LAYN in HPV-related head and neck squamous cell carcinoma and its influence on immune cell infiltration

The Prognostic Value of LAYN in HPV-related head and neck squamous cell carcinoma and its Influence on Immune Cell Infiltration

Tumor Stroma as a Therapeutic Target for Pancreatic Ductal Adenocarcinoma

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