Abstract:Lung cancer is an extremely common cancer and metastatic lung cancer has a greatly low survival rate. Lymphangiogenesis is essential for the development and metastasis of lung cancer. The adipokine angiopoietin-like protein 2 (ANGPTL2) regulates tumor progression and metastasis, although the functions of ANGPTL2 in lung cancer are unknown. Analysis of data from TCGA genomics program, the GEPIA web server and the Oncomine database revealed that higher levels of ANGPTL2 expression were correlated with progressiv… Show more
“…LYM index was developed based on LYM-related genes. LYM is closely associated with LUAD progression and metastasis ( 47 ), and based on the role of LYM in LUAD, we concluded that metastasis, invasiveness, and malignancy were higher in the LUAD patients in the high LYM index group compared to the low LYM index group. We confirmed that the prognosis of LUAD patients with a low LYM index was better than that of patients with a high LYM index, suggesting that LYM was an independent risk factor for LUAD, which is consistent with the findings of previous studies ( 48 – 50 ).…”
BackgroundLymphangiogenesis (LYM) has an important role in tumor progression and is strongly associated with tumor metastasis. However, the clinical application of LYM has not progressed as expected. The potential value of LYM needs to be further developed in lung adenocarcinoma (LUAD) patients.MethodsThe Sequencing data and clinical characteristics of LUAD patients were downloaded from The Cancer Genome Atlas and GEO databases. Multiple machine learning algorithms were used to screen feature genes and develop the LYM index. Immune cell infiltration, immune checkpoint expression, Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and drug sensitivity analysis were used to explore the correlation of LYM index with immune profile and anti-tumor therapy.ResultsWe screened four lymphangiogenic feature genes (PECAM1, TIMP1, CXCL5 and PDGFB) to construct LYM index based on multiple machine learning algorithms. We divided LUAD patients into the high LYM index group and the low LYM index group based on the median LYM index. LYM index is a risk factor for the prognosis of LUAD patients. In addition, there was a significant difference in immune profile between high LYM index and low LYM index groups. LUAD patients in the low LYM index group seemed to benefit more from immunotherapy based on the results of TIDE algorithm.ConclusionOverall, we confirmed that the LYM index is a prognostic risk factor and a valuable predictor of immunotherapy response in LUAD patients, which provides new evidence for the potential application of LYM.
“…LYM index was developed based on LYM-related genes. LYM is closely associated with LUAD progression and metastasis ( 47 ), and based on the role of LYM in LUAD, we concluded that metastasis, invasiveness, and malignancy were higher in the LUAD patients in the high LYM index group compared to the low LYM index group. We confirmed that the prognosis of LUAD patients with a low LYM index was better than that of patients with a high LYM index, suggesting that LYM was an independent risk factor for LUAD, which is consistent with the findings of previous studies ( 48 – 50 ).…”
BackgroundLymphangiogenesis (LYM) has an important role in tumor progression and is strongly associated with tumor metastasis. However, the clinical application of LYM has not progressed as expected. The potential value of LYM needs to be further developed in lung adenocarcinoma (LUAD) patients.MethodsThe Sequencing data and clinical characteristics of LUAD patients were downloaded from The Cancer Genome Atlas and GEO databases. Multiple machine learning algorithms were used to screen feature genes and develop the LYM index. Immune cell infiltration, immune checkpoint expression, Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and drug sensitivity analysis were used to explore the correlation of LYM index with immune profile and anti-tumor therapy.ResultsWe screened four lymphangiogenic feature genes (PECAM1, TIMP1, CXCL5 and PDGFB) to construct LYM index based on multiple machine learning algorithms. We divided LUAD patients into the high LYM index group and the low LYM index group based on the median LYM index. LYM index is a risk factor for the prognosis of LUAD patients. In addition, there was a significant difference in immune profile between high LYM index and low LYM index groups. LUAD patients in the low LYM index group seemed to benefit more from immunotherapy based on the results of TIDE algorithm.ConclusionOverall, we confirmed that the LYM index is a prognostic risk factor and a valuable predictor of immunotherapy response in LUAD patients, which provides new evidence for the potential application of LYM.
“…Precooled Matrigel was added to a 96-well plate and subjected to incubation at 37 °C for 30 min. HUVECs (2 × 10 4 cells/well) were suspended in 200 µL of conditioned medium and subsequently transferred to the corresponding well and incubated with supernatants from specified KTC-1 and BCPAP cells in 5% CO 2 at 37 °C for 8–12 h [ 28 ]. The images of tube structures were detected under an inverted bright-field microscope at 100× magnification, and photographs were taken.…”
Background
Long noncoding RNAs (lncRNAs) are significant contributors to various human malignancies. The aberrant expression of lncRNA LINC00894 has been reported in various human malignancies. We aimed to illustrate the role of LINC00894 and its underlying mechanism in the development of papillary thyroid carcinoma (PTC).
Methods
We performed bioinformatics analysis of differentially expressed RNAs from TCGA and GEO datasets and selected the target lncRNA LINC00894. SRAMP analysis revealed abundant M6A modification sites in LINC00894. Further analysis of StarBase, GEPIA, and TCGA datasets was performed to identify the related differentially expressed genes METTL3. Colony formation and CCK-8 assays confirmed the relationship between LINC00894, METTL3, and the proliferative capacity of PTC cells. The analysis of AnnoLnc2, Starbase datasets, and meRIP-PCR and qRT‒PCR experiments confirmed the influence of METTL3-mediated m6A modification on LINC00894. The study employed KEGG enrichment analysis as well as Western blotting to investigate the impact of LINC00894 on the expression of proteins related to the Hippo signalling pathway.
Results
LINC00894 downregulation was detected in PTC tissues and cells and was even further downregulated in PTC with lymphatic metastasis. LINC00894 inhibits the lymphangiogenesis of vascular endothelial cells and the proliferation of cancer cells. METTL3 enhances PTC progression by upregulating LINC00894 by enhancing LINC00894 mRNA stability through the m6A-YTHDC2-dependent pathway. LINC00894 may inhibit PTC malignant phenotypes through the Hippo signalling pathway.
Conclusion
The METTL3-YTHDC2 axis stabilizes LINC00894 mRNA in an m6A-dependent manner and subsequently inhibits tumour malignancy through the Hippo signalling pathway.
“… 302 – 305 On one hand, VEGFA could function on VEGFR1/2 expressed by LECs and promote lymphanigongenesis. 304 , 305 On the other hand, VEGFA could indirectly induce lymphangiogenesis via recruitment of VEGFR1 + bone marrow-derived macrophages which in turn release both hemangiogenic and lymphangiogenic growth factors. 302 , 303 Fig.…”
Section: Therapeutic Interventions and Clinical Research Progress Of ...mentioning
Lymphatic vessels, comprising the secondary circulatory system in human body, play a multifaceted role in maintaining homeostasis among various tissues and organs. They are tasked with a serious of responsibilities, including the regulation of lymph absorption and transport, the orchestration of immune surveillance and responses. Lymphatic vessel development undergoes a series of sophisticated regulatory signaling pathways governing heterogeneous-origin cell populations stepwise to assemble into the highly specialized lymphatic vessel networks. Lymphangiogenesis, as defined by new lymphatic vessels sprouting from preexisting lymphatic vessels/embryonic veins, is the main developmental mechanism underlying the formation and expansion of lymphatic vessel networks in an embryo. However, abnormal lymphangiogenesis could be observed in many pathological conditions and has a close relationship with the development and progression of various diseases. Mechanistic studies have revealed a set of lymphangiogenic factors and cascades that may serve as the potential targets for regulating abnormal lymphangiogenesis, to further modulate the progression of diseases. Actually, an increasing number of clinical trials have demonstrated the promising interventions and showed the feasibility of currently available treatments for future clinical translation. Targeting lymphangiogenic promoters or inhibitors not only directly regulates abnormal lymphangiogenesis, but improves the efficacy of diverse treatments. In conclusion, we present a comprehensive overview of lymphatic vessel development and physiological functions, and describe the critical involvement of abnormal lymphangiogenesis in multiple diseases. Moreover, we summarize the targeting therapeutic values of abnormal lymphangiogenesis, providing novel perspectives for treatment strategy of multiple human diseases.
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