Purpose: To develop a LRP1B gene mutation based prognostic model for hepatocellular carcinoma (HCC) patients risk prediction. Methods: The LRP1B gene mutation rate was calculated from HCC patient samples. Meanwhile, differentially expressed genes according to LRP1B mutant were screened out for prognostic model establishment. Based on this innovative model, HCC patients were categoried into high and low-risk group. The immune status including immune cell infiltration ratio and checkpoints have been explored in two groups. The functions of LRP1B and risk factors in the model were verified using both in vivo and in vitro experiments. Results: It could be demonstrated that LRP1B was a potential negative predictor for HCC patients prognosis with high mutation frequency. The functions of LRP1B was verified with ELISA assay and Quantitative Real-time PCR method based on clinical recruited HCC participants. 11 genes displayed significant differences according to LRP1B status, which could better predict HCC patient prognosis. The functions of these genes were examined using HCC cell line HCCLM3, suggesting they played a pivotal role in determining HCC cell proliferation and apoptosis. From the immune cell infiltration ratio analysis, there was a significant difference in the infiltration degree of 7 types of immune cells and 2 immune checkpoints between high and low-risk HCC patients. Conclusion: This study hypothesized a potential prognostic biomarker and developed a novel LRP1B mutation-associated prognostic model for hepatocellular carcinoma, which provided a systematic reference for future understanding of clinical research.
Purpose: Oral squamous cell carcinoma (named OSCC) is considered as the most frequent malignancy in oral cavity, which has became a rapid increasing problem for the global public health with unclear underling molecular mechanism. Previously, we reported Tiam1 (T-lymphoma invasion and metastasis inducing factor 1) as a potential oncogene for OSCC. Here, we in-depth explored its signaling mechanism.Methods: The mRNA and protein expression levels of primary differentially expressed genes (Tiam1, Fibulin-3 and MMP-7) were measured in different TNM stages of OSCC patients using RT-PCR and ELISA respectively. Using human OSCC cell line CAL27 cell line, the relationships between these factors have been analyzed and the direct interaction has been also examined. The luciferase reporter assay was established for the promoter region of MMP-7. Both the epithelial (E-cadherin) and mesenchymal protein markers (Vimentin and Snail) have been investigated using western blotting.Results: The mRNA and protein activities of Fibulin-3 declined as the increase of TNM stage. Inversely, the mRNA and protein levels of Tiam1 and MMP-7 elevated signi cantly as OSCC progressed. Tiam1 transfection in CAL27 cells stimulated the expression of MMP-7 by accelerating the nuclear translocation of β-catenin, which was opposite to the functions of Fibulin-3. Moreover, Tiam1 interacted directly with Fibulin-3. The Tiam1 induced OSCC epithelial-mesenchymal transition (EMT) via MMP-7 activation, which was dependent of β-catenin direct binding on the promoter region.Conclusions: Collectively, these results indicated that Tiam1 competed with Fibulin-3 for nuclear βcatenin translocation, which subsequently stimulated MMP-7 expression by TCF-4 domain interaction following EMT initiation in OSCC development. Our systematical work here hypothesized an innovative signaling cassette for OSCC progression, which provided bene cial references for future clinical study.
Purpose: To develop a tumor microenvironment (TME) related genes based prognostic model for laryngeal cancer patients risk prediction. Methods: A innovative prognosic model was generated based on TME related genes (760 genes). Based on the model, laryngeal cancer patients were categoried into high and low-risk group. The immune status including immune cell infiltration ratio as well as checkpoints have been exploreds. Results: It can be shown here 15 genes demonstrate significant differences, which can better predict laryngeal cancer patient prognosis. The accuracy of the model prediction is evaluated and approved by the AUC value. From the immune cell infiltration ratio analysis, there is a significant difference in the infiltration degree of several types of immune cells and 6 immune checkpoints between high and low-risk laryngeal cancer patients. At the same time, the close related genes as well as TME pathways have been also investigated. Conclusion: This study has explored a potential prognostic biomarker and developed a novel TME-associated prognostic model for laryngeal cancer, which provides a valuable reference for future clinical research.
Purpose: Oral squamous cell carcinoma (named OSCC) is considered as the most frequent malignancy in oral cavity, which has became a rapid increasing problem for the global public health with unclear underling molecular mechanism. Previously, we reported Tiam1 (T-lymphoma invasion and metastasis inducing factor 1) as a potential oncogene for OSCC. Here, we in-depth explored its signaling mechanism. Methods: The mRNA and protein expression levels of primary differentially expressed genes (Tiam1, Fibulin-3 and MMP-7) were measured in different TNM stages of OSCC patients using RT-PCR and ELISA respectively. Using human OSCC cell line CAL27 cell line, the relationships between these factors have been analyzed and the direct interaction has been also examined. The luciferase reporter assay was established for the promoter region of MMP-7. Both the epithelial (E-cadherin) and mesenchymal protein markers (Vimentin and Snail) have been investigated using western blotting. Results: The mRNA and protein activities of Fibulin-3 declined as the increase of TNM stage. Inversely, the mRNA and protein levels of Tiam1 and MMP-7 elevated significantly as OSCC progressed. Tiam1 transfection in CAL27 cells stimulated the expression of MMP-7 by accelerating the nuclear translocation of β-catenin, which was opposite to the functions of Fibulin-3. Moreover, Tiam1 interacted directly with Fibulin-3. The Tiam1 induced OSCC epithelial-mesenchymal transition (EMT) via MMP-7 activation, which was dependent of β-catenin direct binding on the promoter region. Conclusions: Collectively, these results indicated that Tiam1 competed with Fibulin-3 for nuclear β-catenin translocation, which subsequently stimulated MMP-7 expression by TCF-4 domain interaction following EMT initiation in OSCC development. Our systematical work here hypothesized an innovative signaling cassette for OSCC progression, which provided beneficial references for future clinical study.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.