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Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
A potential immunotherapeutic and prognostic biomarker for multiple tumors including glioma: SHOX2
Xiaocong Wu1, Hui Chen1, Chao You2
1Department of Neurosurgery, Sichuan Friendship Hospital, 96 Shangshahepu Street, Jinjiang District, Chengdu, Sichuan, 610066, China.
Background:
Short stature homeobox 2 (SHOX2) is significant gene in the development and progression of multiple types of tumors. Nonetheless, the biological role of SHOX2 within pan-cancer datasets has not been investigated. Thus, comprehensive bioinformatics analyses of pan-cancer datasets were conducted to explore how SHOX2 regulates tumorigenesis.
Methods:
A variety of tumor datasets and online analytical tools, including SangerBox, TIMER2, LinkedOmic, GEPIA2 and cBioPortal, were applied to explore SHOX2 expression in various tumors. To ascertain the connections between SHOX2 expression and genetic alterations, SHOX2-related genes and tumor immunity, the pan-cancer datasets were examined. In vitro assays were applied to verify the biological functions of SHOX2 in glioma cells via CCK-8, wound healing, Transwell and colony formation assays.
Results:
Analyses found that SHOX2 was overexpressed in multiple cancer types. SHOX2 expression level was significantly correlated with isocitrate dehydrogenase (IDH), 1p/19q, O6-methylguanine DNA methyltransferase (MGMT) status and new types of glioma patients. High mRNA expression levels of SHOX2 were associated with a poor prognosis in multiple tumor patients. KEGG enrichment analysis showed that SHOX2-related genes were associated with cell cycle and DNA damage repair. Genetic alterations of SHOX2 were identified in multiple types of cancers, including duplications and deep mutations. Immune analysis showed that SHOX2 was closely correlated with the tumor mutation burden (TMB), microsatellite instability (MSI), neoantigen and neoantigens and immune checkpoint (ICP) in a variety of tumors and could influence the immunotherapy sensitivity of cancers. CCK-8, wound healing, Transwell and colony formation experiments showed that SHOX2 knockdown inhibited glioma cell proliferation, migration, invasion and colony formation abilities.
Conclusion:
SHOX2 was overexpressed in multiple cancer types in TCGA cohort. SHOX2 knockdown inhibited glioma cell proliferation, migration and colony formation ability. Our study showed that SHOX2 may be an immunotherapeutic and promising prognostic biomarker in certain types of tumors.
Insights
Short stature homeobox 2 (SHOX2) is overexpressed in many cancers and linked to poor prognosis. Knocking down SHOX2 inhibits glioma cell growth, suggesting SHOX2 as a potential biomarker for cancer therapy.
Area of Science:
- Oncology
- Genetics
- Bioinformatics
Background:
- Short stature homeobox 2 (SHOX2) plays a role in tumor development and progression.
- The biological function of SHOX2 in pan-cancer datasets remains largely unexplored.
Purpose of the Study:
- To comprehensively analyze the role of SHOX2 in tumorigenesis across various cancer types using bioinformatics.
- To investigate the association of SHOX2 with tumor characteristics, prognosis, and immune microenvironment.
Main Methods:
- Utilized TCGA pan-cancer datasets and bioinformatics tools (SangerBox, TIMER2, LinkedOmic, GEPIA2, cBioPortal).
- Examined SHOX2 expression, genetic alterations, and correlations with tumor immunity.
- Performed in vitro assays (CCK-8, wound healing, Transwell, colony formation) in glioma cells.
Main Results:
- SHOX2 is overexpressed in multiple cancers and associated with poor prognosis.
- SHOX2 expression correlates with IDH, 1p/19q, MGMT status, and glioma subtypes.
- SHOX2 influences tumor mutation burden, microsatellite instability, neoantigens, immune checkpoints, and immunotherapy sensitivity.
- SHOX2 knockdown inhibits glioma cell proliferation, migration, invasion, and colony formation.
Conclusions:
- SHOX2 is overexpressed in various cancers within the TCGA cohort.
- SHOX2 knockdown suppresses glioma cell growth and invasion.
- SHOX2 shows potential as a prognostic and immunotherapeutic biomarker for specific cancer types.
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