Identification of genes related to low‐grade glioma progression and prognosis based on integrated transcriptome analysis

Jiang, Yao; He, Jiaxue; Guo, Yongcan; Tao, Hualin; Pu, Fei; Li, Yiqin

doi:10.1002/jcb.29577

Cited by 36 publications

(21 citation statements)

References 65 publications

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“…It has been reported that collagen type V is highly expressed in the matrix of pancreatic ductal adenocarcinoma and may affect the malignant phenotype of various pancreatic cancer cell lines by promoting adhesion, migration, and viability (20). Many studies have demonstrated that COL5A2 is differentially expressed in various tumors and is related to tumor metastasis and poor prognosis (21)(22)(23). However, up to now, the role of COL5A2 in PCa has not been examined.…”

Section: Discussionmentioning

confidence: 99%

COL5A2 Promotes Proliferation and Invasion in Prostate Cancer and Is One of Seven Gleason-Related Genes That Predict Recurrence-Free Survival

et al. 2021

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Extensive research has revealed that the score derived from the Gleason grading system plays a pivotal role in predicting prostate cancer (PCa) progression. However, the underlying involvement of Gleason-related genes in PCa requires further investigation. This study aimed to identify Gleason-related genes with the potential to guide PCa therapy and future research. Differentially expressed genes (DEGs) were identified by comparing PCa tissues with high or low Gleason scores using the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. R v3.6.1, SPSS v23, and ImageJ software were used for all analyses. An effective recurrence-free survival (RFS) predictive model based on seven Gleason-related genes was established and validated (TCGA, AUC = 0.803; five years, AUC = 0.740; three years, AUC = 0.722; one year, AUC = 0.711; GSE46602, AUC = 0.766; five years, AUC = 0.808; three years, AUC = 0.723; one year, AUC = 0.656; GSE116918, AUC = 0.788; five years, AUC = 0.704; three years, AUC = 0.693; one year, AUC = 0.996). Calibration and nomogram plots were conducted. Weighted correlation network analysis (WGCNA) was used, and COL5A2 was selected for further analysis. The results from in vitro experiments demonstrated that COL5A2 was upregulated in PCa with high Gleason scores. The knockdown of COL5A2 inhibited cell proliferation and invasion in PC-3 and LNCaP cell lines. Meanwhile, COL5A2 displayed a strong association with immune infiltration, which might be an underlying immunotherapy target for PCa. We successfully established a robust RFS predictive model. The findings from this study indicated that COL5A2 could promote cell proliferation and invasion in PCa.

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Section: Discussionmentioning

confidence: 99%

COL5A2 Promotes Proliferation and Invasion in Prostate Cancer and Is One of Seven Gleason-Related Genes That Predict Recurrence-Free Survival

et al. 2021

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“…Although a previous study has been found collagen genes were related to the progression and prognosis of LGGs [43], no study has been focused on the correlation between collagen genes and tumor microenvironment of glioma. The tumor microenvironment consists of in ammatory cells, stromal cells, broblasts, vascular endothelial cells, and ECM [44].…”

Section: Discussionmentioning

confidence: 98%

Identification of collagen genes related to immune infiltration and epithelial-mesenchymal transition in glioma

Yin

Tan

Xin

et al. 2020

Preprint

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Background: Gliomas account for the majority of fatal primary brain tumors, and there is much room for research in the underlying pathogenesis, the multistep progression of glioma, and how to improve survival. In our study, we aimed to identify potential biomarkers or therapeutic targets of glioma and study the mechanism underlying the tumor progression. Methods: We downloaded the microarray datasets (GSE43378 and GSE7696) from the Gene Expression Omnibus (GEO) database. Then, we used weighted gene co-expression network analysis (WGCNA) to screen potential biomarkers or therapeutic targets related to the tumor progression. ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumors using Expression data) algorithm and TIMER (Tumor Immune Estimation Resource) database were used to analyze the correlation between the selected genes and the tumor microenvironment. Real-time reverse transcription polymerase chain reaction was used to measure the selected gene. Transwell and wound healing assay were used to measure the cell migration and invasion capacity.Results: We identified specific module genes that were positively correlated with the WHO grade but negatively correlated with OS of glioma. Importantly, we identified that 6 collagen genes (COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, and COL5A2) could regulate the immunosuppressive microenvironment of glioma. Moreover, we found that these collagen genes were significantly involved in the epithelial-mesenchymal transition (EMT) process of glioma. Finally, taking COL5A2 as a further research object, the results showed that knockdown of COL5A2 significantly inhibited the migration and invasion of SHG44 and A172 cells. Conclusions: In summary, our study demonstrated that collagen genes play an important role in regulating the immunosuppressive microenvironment and EMT process of glioma and could serve as potential therapeutic targets for glioma management.

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“…Meanwhile, elevated COL4A1 gene expression has been found to be associated with trastuzumab resistance in GC [27]. Several studied had reported that COL5A2 might function as crucial role in the initiation and progression of tumor by using bioinformatics technologies [28,29]. More importantly, COL5A2, was correlated with stromal scores in GC, promoted the recruitment of circulating monocytes into the TME and facilitated their differentiation into tumor-associated macrophages [30].…”

Section: Discussionmentioning

confidence: 99%

Landscape Of M6a RNA Methylation Regulators and Tumor Microenvironment Cell-Infiltration Characterization In Gastroesophageal Adenocarcinomas

Liu

Zhu

Wang

et al. 2021

Preprint

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Background: RNA N6-methyladenosine (m6A) modification plays a nonnegligible role in shaping individual tumor microenvironment (TME) characterizations. However, the landscape and relationship of m6A modification and TME cell infiltration remain unknown in gastroesophageal adenocarcinomas (GEA). Methods: We systematically examined the TME of GEA focusing on the distinct m6A modification patterns from the public databases. Intrinsic patterns of m6A modification were evaluated for associations with clinicopathological characteristics, underlying biological pathways, tumor immune cell infiltration, oncological outcomes and treatment responses. We generated a single-cell transcriptome atlas of the GEA sample inhouse to validate the role of the m6A modification pattern on TME.Results: We identified and validated the landscape of m6A regulators and tumor-infiltrating immune cells in GEA. Then, two distinct m6A modification patterns of GEA (cluster1/2 subgroup) were defined, and we correlated two subgroups with TME cell-infiltrating characteristics. Cluster2 subgroup correlates with a poorer prognosis, down-regulated PD-1 expression, higher risk scores and distinct immune cell infiltration. Additionally, PPI and WGCNA network analysis were integrated to identify key module genes closely related to immune infiltration of GEA to find immunotherapy markers. And COL4A1 and COL5A2 in brown module were significantly correlated to the prognosis, PD-1/L1 and CTLA-4 expression of GEA patients. Interesting, low COL5A2 expression was linked to an enhanced response to anti-PD-1 immunotherapy. Finally, a prognostic risk score was constructed using three m6A regulator-associated signatures that represented an independent prognosis factor for GEA. The single-cell transcriptome atlas of GEA sample validated the role of m6A modification pattern on TME and revealed that three m6A regulators are highly expressed in CD4+ T cells, CD8+ T cells, Tregs and Macrophages.Conclusions: Our work revealed m6A RNA methylation regulators are a type of vital participant in the malignant progression and TME diversity of GEA. m6A modification patterns of COL5A2 may be the potential biomarker contributes to predicting the response to anti-PD-1 immunotherapy.

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Identification of genes related to low‐grade glioma progression and prognosis based on integrated transcriptome analysis

Cited by 36 publications

References 65 publications

COL5A2 Promotes Proliferation and Invasion in Prostate Cancer and Is One of Seven Gleason-Related Genes That Predict Recurrence-Free Survival

COL5A2 Promotes Proliferation and Invasion in Prostate Cancer and Is One of Seven Gleason-Related Genes That Predict Recurrence-Free Survival

Identification of collagen genes related to immune infiltration and epithelial-mesenchymal transition in glioma

Landscape Of M6a RNA Methylation Regulators and Tumor Microenvironment Cell-Infiltration Characterization In Gastroesophageal Adenocarcinomas

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