Cartilage oligomeric matrix protein is a prognostic factor and biomarker of colon cancer and promotes cell proliferation by activating the Akt pathway

Liu, Tingting; Liu, Xi‐sheng; Zhang, Meng; Liu, Xue-Ni; Zhu, Fuxiang; Zhu, Fangming; Ouyang, Siwen; Li, Shanbao; Song, Chenlong; Sun, Huimin; Lu, Su; Zhang, Yu; Lin, Jun; Tang, Huamei; Peng, Zhihai

doi:10.1007/s00432-018-2626-4

Cited by 56 publications

(62 citation statements)

References 32 publications

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“…It has been suggested as an independent prognostic marker for breast cancer ( 41 ). Liu et al ( 42 ) established COMP-knockout cells to detect the effects of COMP on colon cancer cells and found that knockout of COMP could suppress cells proliferation, clonogenicity, and tumor growth, while increasing sensitivity to chemotherapy. These findings indicate that COMP may be also a potential therapeutic target for cancer.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Immune-Related Genes in the Tumor Microenvironment of Bladder Cancer

Teng

Liu

et al. 2020

Front. Oncol.

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The tumor microenvironment (TME) is a complex system that plays an important role in tumor development and progression, but the current knowledge about its effect on bladder cancer (BC) is scarce. In this study, we performed a comprehensive analysis of the relationship between the TME and gene expression profiles to identify prognostic biomarkers for BC. The ESTIMATE algorithm was used to calculate immune and stromal scores of BC patients who were obtained from the Gene Expression Omnibus database. We found that the immune and stromal scores were associated with clinical characteristics and the prognosis of BC patients. Based on these scores, 104 immune-related differentially expressed genes were identified. Further, functional enrichment analysis revealed that these genes were mainly involved in the immune-related biological processes and signaling pathways. Three prognostic genes were then identified and used to establish a risk prediction model using Cox regression analyses. Kaplan-Meier survival analysis showed that the expression levels of COL1A1, COMP, and SERPINE2 significantly correlated with cancer-specific survival and overall survival of BC patients. Additionally, we validated the prognostic values of these genes using two independent cohorts from The Cancer Genome Atlas and Gene Expression Omnibus databases. Finally, the relationships between the three prognostic genes and several immune cells were evaluated using Tumor Immune Estimation Resource, indicating that the expression levels of COL1A1, COMP, and SERPINE2 correlated positively with the tumor infiltration levels of CD4 + T cells and macrophages. In conclusion, the current study comprehensively analyzed the TME and presented immune-related prognostic genes for BC, providing new insights into immunotherapeutic strategies for BC patients.

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Section: Discussionmentioning

confidence: 99%

Prognostic Value of Immune-Related Genes in the Tumor Microenvironment of Bladder Cancer

Teng

Liu

et al. 2020

Front. Oncol.

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“…Liu et al . 39 reported that COMP is the biomarker for colon cancer and could promote the cell proliferation through Akt pathway. Stracke et al .…”

Section: Discussionmentioning

confidence: 99%

The prognostic value and potential mechanism of Matrix Metalloproteinases among Prostate Cancer

Geng¹,

Chen²,

Huang³

et al. 2020

Int. J. Med. Sci.

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Background: Matrix Metalloproteinases (MMPs) play an indispensable role in the initial alteration and development of PCa. We tried to generate an MMP-related prognostic signature (MMPS) in prostate cancer (PCa). Methods: TCGA-PRAD, MSKCC/GSE21032, GSE116918, GSE70769 cohorts were enrolled to assess the prognostic value of MMPs. The least absolute shrinkage and selection operator (LASSO) Cox regression was employed to generate the MMPS signature. The log-rank test and Kaplan-Meier (K-M) survival curve were applied to show the difference RFS, The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) was plotted to predict the accuracy of signature. CIBERSORT was conducted to analyze the different immune infiltration in MMPS-H and MMPS-L groups. Potential signaling pathways activated in the MMPS-H groups by Metascape. Results: MMP1, MMP7, MMP11, MMP24 and MMP26 were selected by LASSO regression and established the MMPS predict signature. The MMPS showed the high prognostic value in TCGA-PRAD training cohort (AUC=0.714) and validation cohorts (GSE116918: AUC=0.976, GSE70769: AUC=0.738, MSKCC: AUC=0.793). Pid integrin1 pathway, G2M checkpoint, and response to growth factor signaling pathways were activated in MMPS-H group, patients with the high MMPS risk score and low M2 macrophage showed the worst recurrence-free survival (RFS). Conclusion: MMPs involved and played an essential role in the tumorigenesis and biochemical recurrence in PCa patients. The MMPS signature could accurately predict the recurrence of PCa patients and validated in several cohorts.

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“…COMP can reportedly prevent apoptosis by inducing the expression of apoptosis inhibitors 5 - 8 . COMP is also a prognostic factor and biomarker of colon cancer and promotes cell proliferation by activating the Akt pathway 9 , 10 . In addition, COMP initiates cancer stem cells by activating Jagged1-Notch3 signaling 11 .…”

Section: Introductionmentioning

confidence: 99%

Cartilage Oligomeric Matrix Protein promotes epithelial-mesenchymal transition by interacting with Transgelin in Colorectal Cancer

Zhong

Hou

et al. 2020

Theranostics

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Background and Purpose: The role of the cartilage oligomeric matrix protein (COMP) in epithelial-mesenchymal transition (EMT) in tumor progression has been studied, but its exact regulatory mechanism remains unknown. Methods: The interaction between COMP and the actin-binding protein transgelin (TAGLN) was identified by interaction protein prediction and co-immunoprecipitation and verified through the stochastic optical reconstruction microscopy (STORM) and duolink experiments. Western blot and immunofluorescence analyses were conducted to detect the changes in EMT-related markers after COMP overexpression and knockdown. Molecular docking and Biacore of the interaction interface of COMP/TAGLN revealed that Chrysin directly targeted COMP. The promotion of COMP and the Chrysin inhibition of EMT were detected through the cell migration, invasion, apoptosis, and xenotransplantation of nude mice. Results: COMP interacts with TAGLN in EMT in colorectal cancer to regulate cytoskeletal remodeling and promote malignant progression. COMP is highly expressed in highly malignant colorectal cancer and positively correlated with TAGLN expression. COMP knockdown can inhibit colorectal cancer metastasis and invasion, whereas COMP overexpression promotes EMT in colorectal cancer. Through virtual screening of the protein interaction interface, Chrysin, a flavonoid compound extracted from Oroxylum indicum , was found to have the highest docking score to the COMP/TAGLN complex. Chrysin inhibited COMP, thereby preventing EMT and the malignant progression of colorectal cancer. Conclusions: This study illustrated the role of COMP in EMT and suggested that COMP/TAGLN may be a potential tumor therapeutic target. Chrysin exhibits obvious antitumor effects. This work provides a preliminary antitumor therapy to target COMP or its interaction protein to inhibit EMT.

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Cartilage oligomeric matrix protein is a prognostic factor and biomarker of colon cancer and promotes cell proliferation by activating the Akt pathway

Abstract: COMP may be a novel prognostic indicator and biomarker and also a potential therapeutic target for colon cancer.

Cited by 56 publications

References 32 publications

Prognostic Value of Immune-Related Genes in the Tumor Microenvironment of Bladder Cancer

Prognostic Value of Immune-Related Genes in the Tumor Microenvironment of Bladder Cancer

The prognostic value and potential mechanism of Matrix Metalloproteinases among Prostate Cancer

Cartilage Oligomeric Matrix Protein promotes epithelial-mesenchymal transition by interacting with Transgelin in Colorectal Cancer

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