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Thrombospondin-1 is a prognostic biomarker and is correlated with tumor immune microenvironment in glioblastoma.

ABSTRACT: Glioblastoma (GBM) is the most common malignant brain tumor and the most aggressive type of glioma, characterized by strong invasive potential and rapid recurrence despite severe treatment methods, such as maximal tumor resection followed by chemotherapy and radiotherapy. Thrombospondin-1 (THBS1) was first discovered in platelets and subsequent studies have indicated its functions in the development of several cancers, including breast cancer, melanoma, gastric cancer, cervical cancer and GBM. However, to the best of our knowledge, the expression profiles of THBS1 in GBM subtypes remain unknown, and the underlying mechanism by which THBS1 expression is regulated, and its effect on the local immune response in GBM, remains unclear. The present study used public datasets from The Cancer Genome Atlas, the Chinese Glioma Genome Atlas, the Gene Expression Omnibus, the Ivy Glioblastoma Atlas Project, Tumor Immune Estimation Resource, Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data and the Human Protein Atlas to investigate the prognostic value of THBS1 and its expression profiles, as well as its correlation with the local immune response in GBM. The results demonstrated that THBS1 was a biomarker of the pathological malignancy of glioma, and predicted the mesenchymal subtype of GBM. Furthermore, DNA methylation of THBS1 may be an important mechanism by which THBS1 expression is regulated in GBM. The hypomethylation or overexpression of THBS1 predicted an unfavorable prognosis in patients with GBM. Additionally, THBS1 was correlated with immune and inflammatory responses in GBM. Thus, the findings of the present study provide insight into the potential value of THBS1 in the treatment of GBM.

SUBMITTER: Qi C

PROVIDER: S-EPMC7681197 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Thrombospondin-1 is a prognostic biomarker and is correlated with tumor immune microenvironment in glioblastoma.

Qi Chunxiao C Lei Lei L Hu Jinqu J Wang Gang G Liu Jiyuan J Ou Shaowu S

Oncology letters 20201109 1

Glioblastoma (GBM) is the most common malignant brain tumor and the most aggressive type of glioma, characterized by strong invasive potential and rapid recurrence despite severe treatment methods, such as maximal tumor resection followed by chemotherapy and radiotherapy. Thrombospondin-1 (THBS1) was first discovered in platelets and subsequent studies have indicated its functions in the development of several cancers, including breast cancer, melanoma, gastric cancer, cervical cancer and GBM. H ...[more]

PMID: 33240428

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Project description:BackgroundTUBA1C is a microtubule component that is involved in a variety of cancers. Our main objective was to investigate TUBA1C expression, its prognostic value, its potential biological functions, and its impact on the immune system of patients with lung adenocarcinoma (LUAD).MethodsThe Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA) and Immunohistochemistry Analysis were used to analyze TUBA1C expression, its clinicopathology, overall survival (OS), and disease-free survival (DFS) in LUAD patients. We also determined the correlation between TUBA1C and tumor-infiltrating immune cells (TIICs) by using CIBERSORT and GEPIA databases. To determine the expression of TUBA1C in LUAD, we analyzed a collection of immune infiltration levels and cumulative survival of LUAD tissues in TIMER database. By using UALCAN, STRING, and GeneMANIA databases, we investigated the protein-coding genes related to TUBA1C and its co-expression genes in LUAD tissues. Gene set enrichment analysis (GSEA) was performed by using the TCGA dataset.ResultsThe mRNA and the protein expression of TUBA1C were found to be up-regulated in LUAD tissues. The univariate analysis indicated that an increased expression of TUBA1C was significantly correlated to the following parameters: age, stage, and lymph node metastasis. An over-expression of TUBA1C was associated with a poor prognosis of LUAD. In TIMER and CIBERSORT databases, we found that TUBA1C is correlated with 13 types of TIICs: activated B cell, activated CD4 T cell, central memory CD4 T cell, effector memory CD8 T cell, eosinophils, immature B cell, gamma-delta T cell, immature dendritic cell, mast cell, memory B cell, natural killer T cell, regulatory T cell, and type 2T helper cell. By performing GSEA, we found that TUBA1C is closely correlated to cell cycle, p53 signaling pathway, glycolysis, and gluconeogenesis.ConclusionsOur findings indicate that TUBA1C is associated with TIICs in tumor microenvironment. Therefore, it serves as a novel prognostic biomarker and a target for future treatment methods of LUAD.

Project description:Backgrounds: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the second leading cause of death among all cancers. The Ras-associated binding (Rab) proteins constitute the largest family of the Ras superfamily of small GTPases, which mainly mediate membrane trafficking processes. RAB6B is a member of Rab GTPases, and it has been found to be dysregulated in various tumors. However, the clinical significance, correlations with immune cells, and stroma infiltration of RAB6B in HCC remain unclear. Methods: RAB6B mRNA and protein expression in HCC were examined using the TIMER, HCCDB, UALCAN, and HPA databases. The genetic alterations of RAB6B were analyzed by cBioPortal and COSMIC databases. The correlations between RAB6B and tumor-infiltrating immune cells and cancer-associated fibroblasts were explored by using TIMER, TISIDB, and GEPIA databases. Co-expression networks of RAB6B were investigated based on LinkedOmics. Drug sensitivity was analyzed through the GDSC and CTRP databases. RAB6B was knocked down with siRNA in HCC cell lines. EdU assay was performed to detect the cell proliferation ability, flow cytometry was used to compare the differences in the ability of apoptosis, and MTT was used to evaluate the drug sensitivity in vitro. Results: RAB6B mRNA and protein expression were upregulated in the HCC tissues. Kaplan-Meier and Cox regression analyses suggested that highly expressed RAB6B was an independent prognostic factor for poor survival in HCC patients. Moreover, we found that RAB6B expression was positively correlated with the infiltration of immune cells in HCC, including some immunosuppressive cells, chemokines, and receptors, meanwhile RAB6B expression was associated with CD8+T cells exhaustion, resulting in an immunosuppressive microenvironment. Additionally, functional enrichment analysis indicated that RAB6B may be involved in ECM remodeling in the TME, and RAB6B expression was positively associated with CAFs infiltration. Furthermore, RAB6B presented a positive association with sensitivity to GDSC and CTRP drugs. RAB6B knockdown inhibited the cell proliferation and promoted apoptosis and sensitivity to cisplatin of HCC cells in vitro. Conclusion: Our study revealed that RAB6B is a potential biomarker for poor prognosis in HCC patients and correlates with the formation of the immunosuppressive microenvironment in HCC.

Dataset Information

Thrombospondin-1 is a prognostic biomarker and is correlated with tumor immune microenvironment in glioblastoma.

Publications

Thrombospondin-1 is a prognostic biomarker and is correlated with tumor immune microenvironment in glioblastoma.

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