Dataset Information

Comprehensive Analysis of the Prognostic Value and Immune Infiltration of Butyrophilin Subfamily 2/3 (BTN2/3) Members in Pan-Glioma.

ABSTRACT: The BTN2/3 subfamilies are overexpressed in many cancers, including pan-glioma (low- and high-grade gliomas). However, the expression and prognosis of BTN2/3 subfamilies and tumor-infiltrating lymphocytes in pan-glioma remain unknown. In the present study, we systematically explored and validated the expression and prognostic value of BTN2/3 subfamily members in pan-glioma [The Cancer Genome Atlas-glioblastoma and low-grade glioma (TCGA-GBMLGG) merge cohort] using multiple public databases. We used clinical specimens for high-throughput verification and cell lines for qRT-PCR verification, which confirmed the expression profiles of BTN2/3 subfamilies. In addition, the function of the BTN2/3 subfamily members and the correlations between BTN2/3 subfamily expression and pan-glioma immune infiltration levels were investigated. We found that BTN2/3 subfamily members were rarely mutated. BTN2/3 subfamilies were overexpressed in pan-glioma; high expression of BTN2/3 subfamily members was correlated with poor prognosis. In addition, BTN2/3 subfamilies might positively regulate proliferation, and the overexpression of BTN2/3 subfamilies influenced cell cycle, differentiation, and glioma stemness. In terms of immune infiltrating levels, BTN2/3 subfamily expression was positively associated with CD4+ T-cell, B-cell, neutrophil, macrophage, and dendritic cell infiltrating levels. These findings suggest that BTN2/3 subfamily expression is correlated with prognosis and immune infiltration levels in glioma. Therefore, the BTN2/3 subfamilies can be used as biomarkers for pan-glioma and prognostic biomarkers for determining the prognosis and immune infiltration levels in pan-glioma.

SUBMITTER: He D

PROVIDER: S-EPMC9399357 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Comprehensive Analysis of the Prognostic Value and Immune Infiltration of Butyrophilin Subfamily 2/3 (BTN2/3) Members in Pan-Glioma.

He Dong D Qin Zhen Z Liu Zihao Z Ji Xiaoshuai X Gao Jiajia J Guo Hua H Yang Fan F Fan Haitao H Wei Yanbang Y Wang Zixiao Z Liu Qian Q Pang Qi Q

Frontiers in oncology 20220810

The BTN2/3 subfamilies are overexpressed in many cancers, including pan-glioma (low- and high-grade gliomas). However, the expression and prognosis of BTN2/3 subfamilies and tumor-infiltrating lymphocytes in pan-glioma remain unknown. In the present study, we systematically explored and validated the expression and prognostic value of BTN2/3 subfamily members in pan-glioma [The Cancer Genome Atlas-glioblastoma and low-grade glioma (TCGA-GBMLGG) merge cohort] using multiple public databases. We u ...[more]

PMID: 36033440

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Project description:BackgroundFibroblast growth factor receptors (FGFRs) modulate numerous cellular processes in tumor cells and tumor microenvironment. However, the effect of FGFRs on tumor prognosis and tumor-infiltrating lymphocytes in gastric cancer (GC) remains controversial.MethodsThe expression of four different types of FGFRs was analyzed via GEPIA, TCGA-STAD, and GTEX databases and our 27 pairs of GC tumor samples and the adjacent normal tissue. Furthermore, the Kaplan-Meier plot and the TCGA database were utilized to assess the association of FGFRs with clinical prognosis. The R software was used to evaluate FGFRs co-expression genes with GO/KEGG Pathway Enrichment Analysis. In vitro and in vivo functional analyses and immunoblotting were performed to verify FGFR4 overexpression consequence. Moreover, the correlation between FGFRs and cancer immune infiltrates was analyzed by TIMER and TCGA databases. And the efficacy of anti-PD-1 mAb treatment was examined in NOG mouse models with overexpressed FGFR1 or FGFR4.ResultsThe expression of FGFRs was considerably elevated in STAD than in the normal gastric tissues and was significantly correlated with poor OS and PFS. ROC curve showed the accuracy of the FGFRs in tumor diagnosis, among which FGFR4 had the highest ROC value. Besides, univariate and multivariate analysis revealed that FGFR4 was an independent prognostic factor for GC patients. According to a GO/KEGG analysis, the FGFRs were implicated in the ERK/MAPK, PI3K-AKT and extracellular matrix (ECM) receptor signaling pathways. In vivo and in vitro studies revealed that overexpression of FGFR4 stimulated GC cell proliferation, invasion, and migration. In addition, FGFR1 expression was positively correlated with infiltrating levels of CD8+ T-cells, CD4+ T-cells, macrophages, and dendritic cells in STAD. In contrast, FGFR4 expression was negatively correlated with tumor-infiltrating lymphocytes. Interestingly, overexpression of FGFR1 in the NOG mouse model improved the immunotherapeutic impact of GC, while overexpression of FGFR4 impaired the effect. When combined with an FGFR4 inhibitor, the anti-tumor effect of anti-PD-1 treatment increased significantly in a GC xenograft mouse model with overexpressed FGFR4.ConclusionsFGFRs has critical function in GC and associated with immune cell infiltration, which might be a potential prognosis biomarker and predictor of response to immunotherapy in GC.

Project description:AbstractAberrant expression of adenosine triphosphate-binding cassette subfamily C (ABCC), one of the largest superfamilies and transporter gene families of membrane proteins, is associated with various tumors. However, its relationship with liver hepatocellular carcinoma (LIHC) remains unclear.We used the Oncomine, UALCAN, Human Protein Atlas, GeneMANIA, GO, Kyoto Encyclopedia of Genes and Genomes (KEGG), TIMER, and Kaplan-Meier Plotter databases. On May 20, 2021, we searched these databases for the terms ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, ABCC6, ABCC7, ABCC8, ABCC9, ABCC10, ABCC11, ABCC12, ABCC13, and "liver cancer." The exposure group comprised LIHC patients, and the control group comprised normal patients (those with noncancerous liver tissue). All patients shown in the retrieval language search were included. We compared the mRNA expression of these proteins in LIHC and control patients to examine the potential role of ABCC1-13 in LIHC.Relative to the normal liver tissue, mRNA expression of ABCC1/2/3/4/5/6/10 was significantly upregulated (P < .001), and that of ABCC9/11 significantly downregulated (both P < .001), in LIHC. ABCC mRNA expression varied with gender (P < .05), except for ABCC11-13; with tumor grade (P < 0.05), except for ABCC7/12/13; with tumor stage (P < .05), except for ABCC11-13; and with lymph node metastasis status (P < .05), except for ABCC7/8/11/12/13. Based on KEGG enrichment analysis, these genes were associated with the following pathways: ABC transporters, Bile secretion, Antifolate resistance, and Peroxisome (P < .05). Except for ABCC12/13, the ABCCs were significantly associated with B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil, and dendritic cell infiltration (P < .05). High mRNA expression of ABCC1/4/5/8 (P < .05) and low expression of ABCC6/7/9/12/13 (P < .05) indicated poor prognosis. Prognostic significance was indicated for ABCC2/13 for both men and women (P < .05); for ABCC1/6/12/13 for tumor grades 1-3 (P < .05); for ABCC5/11/12/13 for all tumor stages (P < .05); for ABCC1/11/12/13 for American Joint Committee on Cancer T stages 1-3 (P < .05); and for ABCC1/5/6/13 for vascular invasion. None showed prognostic significance for microvascular invasion (P < .05).We identified ABCC1/2/3/4/5/6/9/10/11 as potential diagnostic markers, and ABCC1/4/5/6/7/8/9/12/13 as prognostic markers, of LIHC. Our future work will promote the use of ABCCs in the diagnosis and treatment of LIHC.

Dataset Information

Comprehensive Analysis of the Prognostic Value and Immune Infiltration of Butyrophilin Subfamily 2/3 (BTN2/3) Members in Pan-Glioma.

Publications

Comprehensive Analysis of the Prognostic Value and Immune Infiltration of Butyrophilin Subfamily 2/3 (BTN2/3) Members in Pan-Glioma.

Similar Datasets

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