Dataset Information

SPOCK2 Serves as a Potential Prognostic Marker and Correlates With Immune Infiltration in Lung Adenocarcinoma.

ABSTRACT: Lung adenocarcinoma (LUAD) is one of the major types of lung cancer. Tumor-infiltrating immune cells (TIICs) are positively associated with overall survival (OS) in LUAD. The SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 2 (SPOCK2) is a complex type of secreted proteoglycan involved in forming a protective barrier against viral infection. The purpose of this study was to investigate the relationship between SPOCK2 and TIICs and the prognostic role of SPOCK2 in LUAD. The GEPIA2, GEO, CPTAC, and HPA databases were analyzed to examine both the mRNA and protein expression of SPOCK2 in LUAD. GEPIA2 and the Kaplan-Meier Plotter (KM Plotter) were used to evaluate the prognostic value of SPOCK2 in LUAD patients. TCGA data were examined for a correlation between SPOCK2 expression and clinical characteristics. Gene enrichment analyses were performed to explore the underlying mechanism of SPOCK2 based on LinkedOmics. RegNetwork was used to predict the regulators of SPOCK2. The correlation between SPOCK2 and TIICs, including immune infiltration level and relative proportion was investigated via TIMER. KM Plotter was also used to evaluate the prognostic role of SPOCK2 expression in LUAD with enriched and decreased TIIC subgroups. We found SPOCK2 was significantly downregulated in LUAD compared with that in non-tumor controls and was correlated with clinical parameters. Moreover, a high SPOCK2 expression level predicted better survival. The SPOCK2-associated regulatory network was constructed. SPOCK2 influenced the TIIC infiltration level and relative proportion in LUAD. Furthermore, a high SPOCK2 expression level was associated with a favorable prognosis in enriched CD4 + T cells and macrophage subgroups in LUAD. In conclusion, a high level of SPOCK2 expression predicted favorable prognosis and was significantly correlated with TIICs in LUAD. Therefore, the expression of SPOCK2 may affect the prognosis of LUAD partly due to TIICs.

SUBMITTER: Zhao J

PROVIDER: S-EPMC7683796 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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SPOCK2 Serves as a Potential Prognostic Marker and Correlates With Immune Infiltration in Lung Adenocarcinoma.

Zhao Jinming J Cheng Ming M Gai Junda J Zhang Ruochen R Du Tengjiao T Li Qingchang Q

Frontiers in genetics 20201110

Lung adenocarcinoma (LUAD) is one of the major types of lung cancer. Tumor-infiltrating immune cells (TIICs) are positively associated with overall survival (OS) in LUAD. The SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 2 (SPOCK2) is a complex type of secreted proteoglycan involved in forming a protective barrier against viral infection. The purpose of this study was to investigate the relationship between SPOCK2 and TIICs and the prognostic role of SPOCK2 in LUAD. The GEPIA2, GEO ...[more]

PMID: 33244319

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Project description:Background: aldolase A (ALDOA) has been reported to be involved in kinds of cancers. However, the role of ALDOA in lung adenocarcinoma has not been fully elucidated. In this study, we explored the prognostic value and correlation with immune infiltration of ALDOA in lung adenocarcinoma. Methods: The expression of ALDOA was analyzed with the Oncomine database, the Cancer Genome Atlas (TCGA), and the Human Protein Atlas (HPA). Mann-Whitney U test was performed to examine the relationship between clinicopathological characteristics and ALDOA expression. The receiver operating characteristic (ROC) curve and Kaplan-Meier method were conducted to describe the diagnostic and prognostic importance of ALDOA. The Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape were used to construct PPI networks and identify hub genes. Functional annotations and immune infiltration were conducted. Results: The mRNA and protein expression of ALDOA were higher in lung adenocarcinoma than those in normal tissues. The overexpression of ALDOA was significantly correlated with the high T stage, N stage, M stage, and TNM stage. Kaplan-Meier showed that high expression of ALDOA was correlated with short overall survival (38.9 vs 72.5 months, p < 0.001). Multivariate analysis revealed that ALDOA (HR 1.435, 95%CI, 1.013-2.032, p = 0.042) was an independent poor prognostic factor for overall survival. Functional enrichment analysis showed that positively co-expressed genes of ALDOA were involved in the biological progress of mitochondrial translation, mitochondrial translational elongation, and negative regulation of cell cycle progression. KEGG pathway analysis showed enrichment function in carbon metabolism, the HIF-1 signaling pathway, and glycolysis/gluconeogenesis. The "SCNA" module analysis indicated that the copy number alterations of ALDOA were correlated with three immune cell infiltration levels, including B cells, CD8+ T cells, and CD4+ T cells. The "Gene" module analysis indicated that ALDOA gene expression was negatively correlated with infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, and macrophages. Conclusion: Our study suggested that upregulated ALDOA was significantly correlated with tumor progression, poor survival, and immune infiltrations in lung adenocarcinoma. These results suggest that ALDOA is a potential prognostic biomarker and therapeutic target in lung adenocarcinoma.

Project description:BackgroundThymocyte selection-associated high mobility group box (TOX) plays a crucial role on the development of innate immunity and tumor microenvironment. This study aims to explore the prognostic potential of TOX and comprehensively analyze the correlations between TOX, immune infiltration, and T cells function in diverse cancers particularly lung adenocarcinoma (LUAD).MethodsTIMER was used to analyze TOX expression in different cancers. Potential prognostic value of TOX was evaluated by the PrognoScan, Kaplan-Meier Plotter, and GEPIA2. The relationships between TOX, immune infiltration, and related gene marker sets were analyzed by TIMER and GEPIA2. Single-cell RNA-seq for T cells in LUAD was analyzed to further investigate the correlations between TOX expression and different T cells populations.ResultsTOX downregulates in most of the cancer types and correlates with poor prognosis in LUAD. TOX shows significant impacts on survival of LUAD with early stage, ever-smoking, or low-TMB status. Increased TOX expression positively correlates with high immune infiltration levels in most of the immune cells and functional T cells including exhausted T cells. Moreover, multiple key genes of exhausted T cells comprising PD-1, TIM-3, TIGHT, and CXCL13 have remarkable interaction with TOX. Specifically, TOX is observed with high enrichment in exhausted CD4+ and CD8+ T cells populations in single-cell RNA-seq analysis for LUAD.ConclusionTOX is a prognosis-related biomarker for multiple cancer types especially LUAD. Increased TOX expression significantly increase immune infiltration levels in most of the immune cells comprising CD8+ T cells, CD4+ T cells, mast cells, and functional T cells. Moreover, we verified that TOX highly correlates with exhausted T cells and is probable a critical regulator promoted T cells exhaustion in LUAD. Detection of TOX expression could help to predict prognosis and regulating TOX expression in exhausted T cells may offer a novel strategy in maximizing immunotherapy efficacy for LUAD.

Dataset Information

SPOCK2 Serves as a Potential Prognostic Marker and Correlates With Immune Infiltration in Lung Adenocarcinoma.

Publications

SPOCK2 Serves as a Potential Prognostic Marker and Correlates With Immune Infiltration in Lung Adenocarcinoma.

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