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PGM5 is a promising biomarker and may predict the prognosis of colorectal cancer patients.

ABSTRACT: Background:Phosphoglucomutase (PGM), a key enzyme in the metabolism of glucose-1-phosphate and glucose-6-phosphate, has been found to be associated with proliferation, invasion, and metastasis of cancer. However, the expression and function of PGM5 in colorectal cancer (CRC) remains unknown. Methods:We tested PGM5 mRNA and protein expression levels in 79 CRC tissue and their matched adjacent tissue samples by qRT-PCR and immunohistochemistry, respectively. Overall survival (OS) was estimated with the Kaplan-Meier method and compared between groups with the log-rank test. We performed multivariable Cox regression analyses to identify factors associated with CRC risk. The cell proliferation, migration and invasion abilities of CRC cells were detected by using CCK-8, Transwell migration and invasion assays, respectively. Results:The PGM5 protein levels expression in CRC tissues were significantly lower than those in the adjacent tissues (t?=?5.035, P?

SUBMITTER: Sun Y

PROVIDER: S-EPMC6771116 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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PGM5 is a promising biomarker and may predict the prognosis of colorectal cancer patients.

Sun Yifan Y Long Haihua H Sun Lin L Sun Xiujuan X Pang Liping L Chen Jianlin J Yi Qingqun Q Liang Tianwei T Shen Yongqi Y

Cancer cell international 20191001

<h4>Background</h4>Phosphoglucomutase (PGM), a key enzyme in the metabolism of glucose-1-phosphate and glucose-6-phosphate, has been found to be associated with proliferation, invasion, and metastasis of cancer. However, the expression and function of PGM5 in colorectal cancer (CRC) remains unknown.<h4>Methods</h4>We tested PGM5 mRNA and protein expression levels in 79 CRC tissue and their matched adjacent tissue samples by qRT-PCR and immunohistochemistry, respectively. Overall survival (OS) wa ...[more]

PMID: 31582909

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Project description:Almost all of the extracellular matrix (ECM) components can be degraded by the endoproteinases matrix metalloproteinases (MMPs). Important regulators of MMPs, and thereby of the extracellular environment, are tissue inhibitors of metalloproteinases (TIMPs), and especially TIMP-1. Early tumor development, as well as distant metastasis, may be results of an MMP/TIMP ratio imbalance altering the ECM. MMPs are elevated in several inflammatory conditions. Our aim is to investigate the prognostic role of MMP-8, -?9, and TIMP-1 in colorectal cancer (CRC) and their relationship to inflammation.We included 337 colorectal cancer patients and 47 controls undergoing surgery at Helsinki University Hospital in Finland, 1998-2011. Serum levels of MMP-8 and plasma levels of C-reactive protein (CRP) were determined with a time-resolved immunofluorometric assay (IFMA), and MMP-9 and TIMP-1 with commercial enzyme-linked immunosorbent assay (ELISA) kits. Association and correlation analyses were performed with the Mann-Whitney U, Kruskal-Wallis, and Spearman rank correlation tests. Survival curves were constructed according to the Kaplan-Meier method and compared with the log-rank test.Among patients with advanced disease, serum levels of MMP-8 and TIMP-1 were elevated. CRC patients with high MMP-8 (HR (hazard ratio) 1.72, 95% confidence interval (CI) 1.17-2.52, P?=?0.005) and those with high TIMP-1 (HR 1.80, 95% CI 1.23-2.64, P?=?0.002) had worse prognoses. MMP-9 level failed to serve as a prognostic factor. In multivariable survival analysis, Dukes stage, and low MMP-9/TIMP-1 molar ratio (HR 0.46, 95% CI 0.33-0.98, P?=?0.042) were independently predicted prognosis. A weak correlation between CRP and MMP-8 (rS?=?0.229, P?<?0.001), and TIMP-1 (rS?=?0.280, P?<?0.001) was noted. Among patients showing no systemic inflammatory response, MMP-8 (HR 1.66, 95% CI 1.10-2.53, P?=?0.017) and TIMP-1 (HR 1.59, 95% CI 1.05-2.42, P?=?0.029) were prognostic factors.MMP-8 and TIMP-1 in serum, but not MMP-9, identified CRC patients with bad prognosis. Among patients showing no systemic inflammatory response, MMP-8 and TIMP-1 may associate with poor prognosis.

Project description:BackgroundPyroptosis is a form of cell death characterized by cell swelling and plasma membrane bubbling in association with inflammatory and immune responses. To date, the association between pyroptosis and colorectal cancer remains unclear. We aimed to establish a novel pyroptosis-associated model for the prognosis of colorectal cancer.MethodsPyroptosis-related genes were extracted using Gene Set Enrichment Analysis. A least absolute shrinkage and selection operator regression model was constructed to identify a pyroptosis-related gene signature using the Cancer Genome Atlas and Gene Expression Omnibus databases. Then, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology and GSEA were performed to better understand the potential mechanisms and the functional pathways associated with pyroptosis involved in colorectal cancer. The relationship between the pyroptosis-related signature and immune infiltration was investigated using Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts and MCPcounter.ResultsA 12 pyroptosis-related gene signature was identified. Then, patients were classified into high- and low-risk groups. Kaplan-Meier and receiver operating characteristic analyses confirmed that the high-risk groups showed worse overall survival, progression-free survival, or relapse-free survival probability. Functional enrichment analysis showed that pyroptosis was associated with extracellular matrix-related pathways. Furthermore, the pyroptosis risk score was associated with immune infiltration. The low-risk group exhibited a higher percentage of plasma cells, CD4 T cells, activated dendritic cells, and activated mast cells. M2 macrophages and M0 macrophages were positively related to the risk score.ConclusionOur research yielded a novel pyroptosis-related prognostic signature for colorectal cancer that was related to immune cell infiltration, and it provided an immunological perspective for developing personalized therapies.

Dataset Information

PGM5 is a promising biomarker and may predict the prognosis of colorectal cancer patients.

Publications

PGM5 is a promising biomarker and may predict the prognosis of colorectal cancer patients.

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