Upregulation of COL8A1 indicates poor prognosis across human cancer types and promotes the proliferation of gastric cancer cells

Zhou, Jun; Song, Yaning; Gan, Wei; Liu, Liye; Chen, Guibing; Chen, Zhen‐Yu; Luo, Guangnan; Zhang, Lin; Zhang, Guohu; Wang, Peihong; Cao, Yongkuan

doi:10.3892/ol.2020.11895

Cited by 15 publications

(10 citation statements)

References 32 publications

(41 reference statements)

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“…There are very few studies of COL8A1 in gastric cancer. Experiments on gastric cancer cells show that the silence of COL8A1 can obviously inhibit cell proliferation, migration, and invasion in GC [ 31 ]. We have verified through immunohistochemical analysis that the expression of COL8A1 in GC tissues is distinctly higher than that in normal tissues, and COL8A1 is significantly related to pathological T staging and lymph node metastasis, which suggests that COL8A1 expression may play a part in the progression of gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

COL8A1 Predicts the Clinical Prognosis of Gastric Cancer and Is Related to Epithelial‐Mesenchymal Transition

She

Zhao

et al. 2022

BioMed Research International

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Background. Gastric cancer (GC) is the fifth most common malignant tumor and the third leading cause of cancer-related deaths. Because GC has the characteristics of high heterogeneity, unclear mechanism, limited treatment methods, and low five-year survival rate, it is necessary to find the prognostic biomarkers of GC and explore the mechanism of GC. Methods. We first identified differentially expressed genes (DEGs) between gastric cancer and normal gastric cells through expression analysis. A protein-protein interaction (PPI) network was constructed to find tightly connected modules. We performed survival analysis on the DEGs in the modules to identify genes with prognostic significance. Gene set enrichment analysis (GSEA) was used to identify gene enrichment pathways. Finally, we used our own collected clinical samples of 119 gastric adenocarcinoma (STAD) tissues and 40 normal gastric tissues to perform immunohistochemical (IHC) staining to verify the differential expression of COL8A1 in STAD tissues and normal gastric tissues and its correlation with epithelial-mesenchymal transition- (EMT-) related factors. Results. We identified 356 DEGs through differential expression analysis. Through PPI analysis and survival analysis, we determined that the collagen type VII alpha-1 chain (COL8A1) gene has prognostic significance. GSEA analysis showed that COL8A1 was significantly enriched in the EMT. IHC results showed that COL8A1 was upregulated in STAD tissues and could be used as an independent prognostic factor and was related to EMT. Conclusion. This study shows that COL8A1 is related to the prognosis of GC patients and might affect the progress of GC through the EMT pathway. Therefore, COL8A1 may be a biomarker for predicting the prognosis of GC.

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Section: Discussionmentioning

confidence: 99%

COL8A1 Predicts the Clinical Prognosis of Gastric Cancer and Is Related to Epithelial‐Mesenchymal Transition

She

Zhao

et al. 2022

BioMed Research International

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“…With respect to the four identified markers in the model, elevated expression of COL8A1 has been found in CAFs and was significantly associated with a high risk of death in head and neck squamous cell carcinoma (Lai et al, 2019). Zhang et al identified COL8A1 as the prognostic hub gene highly correlated with Wnt2, which is elevated selectively in CAFs, and high coexpression of COL8A1 and Wnt2 was an independent adverse prognostic factor for colon cancer patients (Katoh, 2001;Zhang et al, 2020) proliferation and promoted the apoptosis of GC cells (Zhou et al, 2020). As for SPOCK1, studies have proved SPOCK1 as an EMT-related marker that was closely correlated with tumorigenesis and invasiveness in gastric cancer (Yan et al, 2017;Chen et al, 2018), prostate cancer (Wang et al, 2016), pancreatic cancer (Li et al, 2020), gallbladder cancer (Shu et al, 2015), and lung cancer (Miao et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Weighted Gene Co-expression Network Analysis Identifies a Cancer-Associated Fibroblast Signature for Predicting Prognosis and Therapeutic Responses in Gastric Cancer

Zheng

Liu

et al. 2021

Front. Mol. Biosci.

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Background: Cancer-associated fibroblasts (CAFs) are the most prominent cellular components in gastric cancer (GC) stroma that contribute to GC progression, treatment resistance, and immunosuppression. This study aimed at exploring stromal CAF-related factors and developing a CAF-related classifier for predicting prognosis and therapeutic effects in GC.Methods: We downloaded mRNA expression and clinical information of 431 GC samples from Gene Expression Omnibus (GEO) and 330 GC samples from The Cancer Genome Atlas (TCGA) databases. CAF infiltrations were quantified by the estimate the proportion of immune and cancer cells (EPIC) method, and stromal scores were calculated via the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Stromal CAF-related genes were identified by weighted gene co-expression network analysis (WGCNA). A CAF risk signature was then developed using the univariate and least absolute shrinkage and selection operator method (LASSO) Cox regression model. We applied the Spearman test to determine the correlation among CAF risk score, CAF markers, and CAF infiltrations (estimated via EPIC, xCell, microenvironment cell populations-counter (MCP-counter), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms). The TIDE algorithm was further used to assess immunotherapy response. Gene set enrichment analysis (GSEA) was applied to clarify the molecular mechanisms.Results: The 4-gene (COL8A1, SPOCK1, AEBP1, and TIMP2) prognostic CAF model was constructed. GC patients were classified into high– and low–CAF-risk groups in accordance with their median CAF risk score, and patients in the high–CAF-risk group had significant worse prognosis. Spearman correlation analyses revealed the CAF risk score was strongly and positively correlated with stromal and CAF infiltrations, and the four model genes also exhibited positive correlations with CAF markers. Furthermore, TIDE analysis revealed high–CAF-risk patients were less likely to respond to immunotherapy. GSEA revealed that epithelial–mesenchymal transition (EMT), TGF-β signaling, hypoxia, and angiogenesis gene sets were significantly enriched in high–CAF-risk group patients.Conclusion: The present four-gene prognostic CAF signature was not only reliable for predicting prognosis but also competent to estimate clinical immunotherapy response for GC patients, which might provide significant clinical implications for guiding tailored anti-CAF therapy in combination with immunotherapy for GC patients.

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“…The gene COL8A1 is highly expressed in GC and is associated with shorter overall survival. Collagen, type VIII, alpha 1 (COL8A1) participates in the malignant biological behavior of GC by promoting the proliferation of GC cells and inhibiting their apoptosis [ 28 ]. The transmembrane prostate androgen-inducible protein 1 (PMEPA1) is a single-pass transmembrane protein that is functionally involved in the TGF-β signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Prognostic marker identification based on weighted gene co-expression network analysis and associated in vitro confirmation in gastric cancer

et al. 2021

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The aim of this study was to explore the potential molecular mechanisms of Gastric cancer (GC) and identify new prognostic markers for GC. RNA sequencing data were downloaded from the Gene Expression Omnibus database, and 418 differentially expressed genes (DEGs) were screened. Weighted correlation network analysis (WGCNA) was performed to identify six hub modules related to the clinical features of GC. Cytoscape software was used to identify five hub genes in the coexpression network, including CST1, CEMIP, COL8A1, PMEPA1, and MSLN. The TCGA database was used to verify hub gene expression in GC. The overall survival in the high CEMIP expression group was significantly lower than that of patients in the low CEMIP expression group. CEMIP expression was also found to be negatively correlated with B cell and CD4 + T cell infiltration. Further, associated in vitro experiments confirmed that CEMIP downregulation suppressed the proliferation and migration of GC cells and impaired the chemoresistance of GC cells to 5-fluorouracil.Our study effectively identified and validated prognostic biomarkers for GC, laying a new foundation for the therapeutic target, occurrence, and development of gastric cancer.

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Upregulation of COL8A1 indicates poor prognosis across human cancer types and promotes the proliferation of gastric cancer cells

Cited by 15 publications

References 32 publications

COL8A1 Predicts the Clinical Prognosis of Gastric Cancer and Is Related to Epithelial‐Mesenchymal Transition

COL8A1 Predicts the Clinical Prognosis of Gastric Cancer and Is Related to Epithelial‐Mesenchymal Transition

Weighted Gene Co-expression Network Analysis Identifies a Cancer-Associated Fibroblast Signature for Predicting Prognosis and Therapeutic Responses in Gastric Cancer

Prognostic marker identification based on weighted gene co-expression network analysis and associated in vitro confirmation in gastric cancer

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