Dataset Information

TOX3 is a favorable prognostic indicator and potential immunomodulatory factor in lung adenocarcinoma.

ABSTRACT: Thymocyte selection-associated high mobility group box (TOX) genes represent a novel family of genes. Deregulated expression of TOXs has been reported in a variety of cancer types, including lung cancer. It has also been reported that TOXs are crucial regulators of the immune system. The present study systematically evaluated the prognostic values of TOX family members using a set of publicly accessible databases, including Oncomine, Kaplan-Meier plotter and cBioPortal. It was revealed that TOX expression profiles differed between lung cancer and normal tissues, and high expression of TOX mRNAs generally predicted improved survival outcomes. Notably, TOX3 expression was significantly increased in lung adenocarcinoma, compared with other pathological subtypes of lung cancer. Survival analysis demonstrated that elevated TOX3 expression was significantly associated with improved progression-free and overall survival in patients with lung adenocarcinoma. Furthermore, correlation analysis indicated that TOX3 expression was negatively correlated with the expression of programmed death-1 receptor (PD-1), PD-ligand 1 and Hepatitis A virus cellular receptor 2 in lung adenocarcinoma. These results indicated that TOX3 is a prognostic indicator and promising immunomodulatory factor in lung adenocarcinoma. Future studies investigating the role of TOX3 in lung cancer immunity are warranted.

SUBMITTER: Zeng

PROVIDER: S-EPMC6732997 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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TOX3 is a favorable prognostic indicator and potential immunomodulatory factor in lung adenocarcinoma.

Zeng De Lin Haoyu H Cui Jianxiong J Liang Weiquan W

Oncology letters 20190816 4

Thymocyte selection-associated high mobility group box (TOX) genes represent a novel family of genes. Deregulated expression of TOXs has been reported in a variety of cancer types, including lung cancer. It has also been reported that TOXs are crucial regulators of the immune system. The present study systematically evaluated the prognostic values of TOX family members using a set of publicly accessible databases, including Oncomine, Kaplan-Meier plotter and cBioPortal. It was revealed that TOX ...[more]

PMID: 31516613

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Project description:BackgroundTumor-infiltrating lymphocytes (TILs) are one of the major participants in the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of interaction between TILs and tumors is complex and remains unclear.ObjectiveTo evaluate the state of immunoreactions in PDAC tissues, and explore the prognostic value of these markers in a large sample, to provide a new theoretical basis for PDAC immunotherapy.MethodImmunohistochemical staining of CD4+ and CD8+T cells was performed in a tissue microarray (TMA) of 143 cases of PDAC. Two major variables for the spatial distributions of CD4+T and CD8+T cells in PDAC tissues, intraepithelial attack and intratumoral infiltration, were used to evaluate the state of immunoreactions, and the interrelationships with the clinicopathological variables were analyzed.ResultsOur data showed that both the intraepithelial CD4+T and CD8+T attack were less frequent than the intratumoral infiltration. CD8+T intraepithelial attack and intratumoral infiltration were more intense than CD4+T. CD8+T intraepithelial attack was an independent favorable prognostic factor for overall survival, correlating negatively with vascular invasion and positively with CD4+T and CD8+T high intratumoral infiltration. CD8+T high intratumoral infiltration without CD8+T intraepithelial attack was a poor prognostic factor. CD8+T high intratumoral infiltration was accompanied by T stage progression. Conclusively, in PDAC progression, imbalances of T cells occurred in CD4+ and CD8+ immunoreactions. The CD8+T intraepithelial attack was an independent favorable prognostic indicator, however the intraepithelial attack of CD4+T and the both intratumoral infiltration of CD8+T and CD4+T played an ambiguous role.ConclusionOur data suggested that it is a potential approach to increasing the number of intraepithelial attacking CD8+T cells for tumor immunotherapy, and exploring a new mechanism for immunosuppression in a tumor microenvironment with high T cell infiltration without attack.

Project description:BackgroundGlucosamine-Phosphate N-Acetyltransferase 1 (GNPNAT1) is a critical enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine. It has many important functions, such as protein binding, monosaccharide binding, and embryonic development and growth. However, the role of GNPNAT1 in lung adenocarcinoma (LUAD) remains unclear.MethodsIn this study, we explored the expression pattern and prognostic value of GNPNAT1 in LUAD across TCGA and GEO databases and assessed its independent prognostic value via Cox analysis. LinkedOmics and GEPIA2 were applied to investigate coexpression and functional networks associated with GNPNAT1. The TIMER web tool was deployed to assess the correlation between GNPNAT1 and the main six types of tumor-infiltrating immune cells. Besides, the correlations between GNPNAT1 and the LUAD common genetic mutations, TMB, and immune signatures were examined.ResultsGNPNAT1 was validated upregulated in tumor tissues in TCGA-LUAD and GEO cohorts. Moreover, in both TCGA and GEO cohorts, high GNPNAT1 expression was found to be associated with poor overall survival. Cox analysis showed that high GNPNAT1 expression was an independent risk factor for LUAD. Functional network analysis suggested that GNPNAT1 regulates cell cycle, ribosome, proteasome, RNA transport, and spliceosome signaling through pathways involving multiple cancer-related kinases and E2F family. In addition, GNPNAT1 correlated with infiltrating levels of B cells, CD4+ T cells, and dendritic cells. B cells and dendritic cells could predict the outcome of LUAD, and B cells and CD4+ T cells were significant independent risk factors. The TMB and mutations of KRAS, EGFR, STK11, and TP53 were correlated with GNPNAT1. At last, the correlation analysis showed GNPNAT1 correlated with most of the immune signatures we performed.ConclusionOur findings showed that GNPNAT1 was correlated to the prognosis and immune infiltration of LUAD. In particular, the tight relationship between GNPNAT1 and B cell marker genes may be the epicenter of the immune response and one of the key factors affecting the prognosis. Our findings laid the foundation for further research on the immunomodulatory role of GNPNAT1 in LUAD.

Dataset Information

TOX3 is a favorable prognostic indicator and potential immunomodulatory factor in lung adenocarcinoma.

Publications

TOX3 is a favorable prognostic indicator and potential immunomodulatory factor in lung adenocarcinoma.

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