Dataset Information

A pan-cancer analysis of thioredoxin-interacting protein as an immunological and prognostic biomarker.

ABSTRACT:

Background

The critical role of thioredoxin-interacting protein (TXNIP) in cellular sulfhydryl redox homeostasis and inflammasome activation is already widely known, however, no pan-cancer analysis is currently available.

Methods

We thus first explored the potential roles of TXNIP across thirty-three tumors mainly based on The Cancer Genome Atlas and Gene Expression Omnibus datasets.

Results

TXNIP is lowly expressed in most cancers, and distinct associations exist between TXNIP expression and the prognosis of tumor patients. TXNIP expression was associated with tumor mutational burden, microsatellite instability, mismatch repair genes, tumor infiltrating immune cell abundance as well as cancer-associated fibroblasts. Moreover, ubiquitin mediated proteolysis, protein post-translational modification and other related pathways were involved in the functional mechanisms of TXNIP.

Conclusions

Our first pan-cancer study comprehensively revealed the carcinostatic role of TXNIP across different tumors. And this molecule may be considered as a potential immunological and prognostic biomarker.

SUBMITTER: Guo X

PROVIDER: S-EPMC9288722 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

A pan-cancer analysis of thioredoxin-interacting protein as an immunological and prognostic biomarker.

Guo Xuxue X Huang Mei M Zhang Haonan H Chen Qianhui Q Hu Ying Y Meng Yan Y Wu Changjie C Tu Chenge C Liu Yongfeng Y Li Aimin A Li Qingyuan Q Zhou Peirong P Liu Side S

Cancer cell international 20220717 1

<h4>Background</h4>The critical role of thioredoxin-interacting protein (TXNIP) in cellular sulfhydryl redox homeostasis and inflammasome activation is already widely known, however, no pan-cancer analysis is currently available.<h4>Methods</h4>We thus first explored the potential roles of TXNIP across thirty-three tumors mainly based on The Cancer Genome Atlas and Gene Expression Omnibus datasets.<h4>Results</h4>TXNIP is lowly expressed in most cancers, and distinct associations exist between T ...[more]

PMID: 35843949

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Project description:BackgroundRING finger protein 43 (RNF43), an E3 ubiquitin ligase, is a homologous gene mutated in several cancers. However, the pan-cancer panoramic picture of RNF43 and its predictive value for tumor immune phenotypes and immunotherapeutic efficacy are still largely unclear. Our study aims to clarify the functions of RNF43 in predicting the prognosis, immune signature, and immunotherapeutic efficacy in pan-cancer.MethodsBy using RNA-seq, mutation, and clinical data from the TCGA database, the expression levels and prognostic significance of RNF43 in pan-cancer were analyzed. The genetic alteration characteristics of RNF43 were displayed by the cBioPortal database. Gene Set Enrichment Analysis (GSEA) was performed to investigate the potential biological functions and signaling pathways modulated by RNF43 in cancers. The relationship of RNF43 expression with immune cell infiltration, and immune modulators expression was interpreted by the ESTIMATE algorithm, CIBERSORT algorithm, and TISIDB database. The correlations between RNF43, microsatellite instability (MSI), and tumor mutation burden (TMB) were also investigated. Furthermore, the predictive value of RNF43 for immunotherapeutic efficacy and drug sensitivity was further illustrated. Besides, immunohistochemistry (IHC) was employed to validate the expression of the RNF43 in different cancer types by our clinical cohorts, including patients with lung cancer, sarcoma, breast cancer, and kidney renal clear cell carcinoma.ResultsThe results demonstrated that RNF43 was abnormally expressed in multiple cancers, and RNF43 is a critical prognosis-related factor in several cancers. RNF43 was frequently mutated in several cancers with a high frequency of 4%, and truncating mutation was the most frequent RNF43 mutation type. RNF43 expression was linked to the abundance of several immune cell types, including CD8+ T cells, B cells, and macrophages within the tumor immune microenvironment. Furthermore, RNF43 expression was significantly correlated with the efficacy of anti-PD-1/PD-L1 treatment, and it could predict the sensitivity of various anti-cancer drugs. Finally, IHC explored and validated the different expression levels of RNF43 in different cancers by our clinical samples.ConclusionOur results first present the expression pattern and the mutation signature of RNF43, highlighting that RNF43 is an important prognostic biomarker in pan-cancer. Furthermore, RNF43 seems to be a critical modulator in the tumor immune microenvironment and can function as a promising biomarker for predicting the immunotherapeutic efficacy of anti-PD-1/PD-L1 treatment, and drug sensitivity in cancer treatment.

Dataset Information

A pan-cancer analysis of thioredoxin-interacting protein as an immunological and prognostic biomarker.

Background

Methods

Results

Conclusions

Publications

A pan-cancer analysis of thioredoxin-interacting protein as an immunological and prognostic biomarker.

Similar Datasets

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