Pyroptosis impacts the prognosis and treatment response in gastric cancer via immune system modulation.
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ABSTRACT:
SUBMITTER: Yang W
PROVIDER: S-EPMC9077078 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
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Pyroptosis impacts the prognosis and treatment response in gastric cancer via immune system modulation.
Yang Wanli W Niu Liaoran L Zhao Xinhui X Duan Lili L Wang Xiaoqian X Li Yiding Y Chen Junfeng J Zhou Wei W Zhang Yujie Y Fan Daiming D Hong Liu L
American journal of cancer research 20220415 4
Pyroptosis plays a vital role in the development of cancers; however, its role in regulating immune cell infiltration in tumor microenvironment (TME) and pyroptosis-related molecular subtypes remain unclear. Herein, we comprehensively analyzed the molecular subtypes mediated by the pyroptosis-related genes (PRGs) in gastric cancer (GC). Three pyroptosis patterns were determined with distinct TME cell-infiltrating characteristics and prognosis. Principal component analysis was performed to establ ...[more]
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Project description:BackgroundAt present intraocular pressure (IOP) lowering therapies are the only approach to treat glaucoma. Neuroprotective strategies to protect the retinal ganglion cells (RGC) from apoptosis are lacking to date. Substantial amount of research concerning the role of the immune system in glaucoma has been performed in the recent years. This review aims to analyse changes found in the peripheral immune system, as well as selected local changes of retina immune cells in the glaucomatous retina.MethodsBy dividing the immune system into the innate and the adaptive immune system, a systematic literature research was performed to find recent approaches concerning the modulation of the immune system in the context of glaucoma. Also ClinicalTrials.gov was assessed to identify studies with a translational context.ResultsWe found that some aspects of the immune system, such as changes in antibody levels, changes in toll like receptor signalling, T cells and retinal microglial cells, experience more research activity than other areas such as changes in dendritic cells or macrophages. Briefly, results from clinical studies revealed altered immunoreactivities against retinal and optic nerve antigens in sera and aqueous humor of glaucoma patients and point toward an autoimmune involvement in glaucomatous neurodegeneration and RGC death. IgG accumulations along with plasma cells were found localised in human glaucomatous retinae in a pro-inflammatory environment possibly maintained by microglia. Animal studies show that antibodies (e.g. anti- heat shock protein 60 and anti-myelin basic protein) elevated in glaucoma patients provoke autoaggressive RGC loss and are associated with IgG depositions and increased microglial cells. Also, studies addressing changes in T lymphocytes, macrophages but also local immune responses in the retina have been performed and also hold promising results.ConclusionsThis recapitulation of recent literature demonstrates that the immune system definitely plays a role in the pathogenesis of glaucoma. Multiple changes in the peripheral innate as well as adaptive immune system have been detected and give room for further research concerning valuable therapeutic targets. We conclude that there still is a great need to bring together the results derived from basic research analysing different aspects of the immune system in glaucoma to understand the immune context of the disease. Furthermore local immune changes in the retina of glaucoma patients still leave room for further therapeutic targets.
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Project description:Gastric cancer (GC) is a malignant tumor with a low survival rate, high recurrence rate, and poor prognosis. With respect to this, pyroptosis is a type of programmed cell death that can affect the occurrence and development of tumors. Indeed, long non-coding RNAs (lncRNAs) were broadly applied for the purposes of early diagnosis, treatment, and prognostic analysis in regard to cancer. Based on the association of these three purposes, we developed a novel prognosis risk model based on pyroptosis-related lncRNAs (PRlncRNAs) for GC. The PRlncRNAs were obtained via univariate and multivariate Cox regression in order to build the predictive signatures. The Kaplan-Meier and gene set enrichment analysis (GSEA) methods were used to evaluate the overall survival (OS) and functional differences between the high- and low-risk groups. Moreover, the correlation of the signatures with immune cell infiltration was determined through single-sample gene set enrichment analysis (ssGSEA). Finally, we analyzed this correlation with the treatment responses in the GC patients; then, we performed quantitative reverse transcription polymerase chain reactions (qRT-PCRs) in order to verify the risk model. The high-risk group received a worse performance in terms of prognosis and OS when compared to the low-risk group. With respect to this, the area under the receiver operating characteristic curve (ROC) was found to be 0.808. Through conducting the GSEA, it was found that the high-risk groups possessed a significant enrichment in terms of tumor-immunity pathways. Furthermore, the ssGSEA revealed that the predictive features possessed strong associations with immune cell infiltration in regard to GC. In addition, we highlighted that anti-immune checkpoint therapy, combined with conventional chemotherapy drugs, may be more suitable for high-risk patients. The expression levels of LINC01315, AP003392.1, AP000695.2, and HAGLR were significantly different between the GC cell lines and the normal cell lines. As such, the six PRlncRNAs could be regarded as important prognostic biomarkers for the purposes of subsequent diagnoses, treatments, prognostic predictions, and the mechanism research of GC.
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