Dataset Information

PPP1R14B Is a Prognostic and Immunological Biomarker in Pan-Cancer.

ABSTRACT: Recent studies have shown that PPP1R14B was highly expressed in tumor tissues and patients with high expression of PPP1R14B had poor survival rates. However, the function and mechanisms of PPP1R14B in tumor progression remain ill defined. There was also lack of pan-cancer evidence for the relationship between PPP1R14B and various tumor types based on abundant clinical data. We used the TCGA project and GEO databases to perform pan-cancer analysis of PPP1R14B, including expression differences, correlations between expression levels and survival, genetic alteration, immune infiltration, and relevant cellular pathways, to investigate the functions and potential mechanisms of PPP1R14B in the pathogenesis or clinical prognosis of different cancers. Herein, we found that PPP1R14B was involved in the prognosis of pan-cancer and closely related to immune infiltration. Increased PPP1R14B expression correlated with poor prognosis and increased immune infiltration levels in myeloid-derived suppressor cells (MDSCs). Our studies suggest that PPP1R14B can be used as a prognostic biomarker for pan-cancer. Our findings may provide an antitumor strategy targeting PPP1R14B, including manipulation of tumor cell growth or the tumor microenvironment, especially myeloid-derived suppressor cell infiltration.

SUBMITTER: Deng M

PROVIDER: S-EPMC8631915 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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PPP1R14B Is a Prognostic and Immunological Biomarker in Pan-Cancer.

Deng Mingxia M Peng Long L Li Jiamin J Liu Xiong X Xia Xichun X Li Guangqiang G

Frontiers in genetics 20211111

Recent studies have shown that PPP1R14B was highly expressed in tumor tissues and patients with high expression of PPP1R14B had poor survival rates. However, the function and mechanisms of PPP1R14B in tumor progression remain ill defined. There was also lack of pan-cancer evidence for the relationship between PPP1R14B and various tumor types based on abundant clinical data. We used the TCGA project and GEO databases to perform pan-cancer analysis of PPP1R14B, including expression differences, co ...[more]

PMID: 34858479

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Project description:SLMO2 is a lipid transporter that transports phosphatidylserine to the interior of mitochondria, also known as PRELID3B, which plays an important role in lipid metabolism. It has also been reported to be involved in the growth process of breast and lung tumors. However, its functions and underlying mechanisms in cancer progress remain elusive, and the potential as pan-cancer biomarker and therapeutic target remains unexplored. Using the TCGA project and GEO database, we performed pan-cancer analysis of SLMO2, which including the expression pattern, prognostic value, mutation landscape, methylation modification, protein-protein interaction network and the relationship between SLMO2 expression and immune infiltration. KEGG enrichment analysis was also performed to predict function and relevant cellular pathways of SLMO2. In addition, proliferation and migration assays were performed to detect the proliferation and metastasis capacity of breast cancer and lung cancer cells. In our study, we found that SLMO2 was overexpressed in pan-cancer and the elevated expression of SLMO2 was correlated with poorer prognosis. SLMO2 mutations were distributed in a variety of tumors and correlated with prognosis. Promoter methylation analysis showed that SLMO2 methylation levels were lower in most tumors compared with normal tissues, while a few tumors showed increased methylation levels of SLMO2. SLMO2 expression was also positively correlated with immune infiltration of MDSCs. Further pathway enrichment analysis indicated that SLMO2 was involved in regulating of cytoplasmic transport and other oncogenic processes. In vitro experiments have shown that SLMO2 promotes the proliferation and migration of breast cancer and lung cancer cells. In conclusion, our findings suggested that SLMO2 was a potential prognostic and immunological marker in pan-cancer. This study suggested a potential strategy for targeting SLMO2 to treat tumors, including manipulating tumor growth or the tumor microenvironment, especially the infiltration of MDSC.

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

PPP1R14B Is a Prognostic and Immunological Biomarker in Pan-Cancer.

Publications

PPP1R14B Is a Prognostic and Immunological Biomarker in Pan-Cancer.

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