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Cancer Informatics
Published in Trevor F. Cox, Medical Statistics for Cancer Studies, 2022
Figure10.12 shows a principal components analysis (PCA) plot of the genes, using the first and second principal components. Figure 10.13 shows non-metric MDS plot for the genes. The plots are similar when the y-axis of one of them is reversed, i.e. y-values multiplied by -1. Looking at the MDS plot, we note that the genes on the left hand side of the plot, MAGE genes, ANGPT1, EGF, MMP19 and ITGA4, are associated with cell matrix remodelling and surface adhesion (cell scaffolding and the binding of cells) and angiogenesis (growing a blood supply for the cell). At the top, KIT is a proto-oncogene involved with cell signalling. Close by, CDH1 is a tumour suppressor gene involved with cell adhesion, away from EGF which is also involved with cell adhesion, but is a proto-oncogene. On the right hand side of the plot, NRAS, CDK and PTEN are involved with the cell cycle, and B2M makes a protein found on cell surfaces mainly on tumour cells.
Comprehensive analysis of matrix metalloproteinases and their inhibitors in head and neck squamous cell carcinoma
Published in Acta Oncologica, 2022
Mingyuan Zou, Chen Zhang, Yan Sun, Huina Wu, Feng Xiao, Wei Gao, Fengfeng Zhao, Xiaobo Fan, Guoqiu Wu
MMPs are a family member of calcium- and zinc-dependent endopeptidases involved in extracellular matrix (ECM) proteins, including collagen, fibronectin, laminin, elastin, and proteoglycans [11,12]. Because of their ability to degrade the ECM, MMPs are elevated in several human patient tumor samples, including ovarian cancer [13,14], prostate cancer [15], and breast cancer [16], and MMP levels are positively correlated with cancer progression. To date, 24 members of the MMP family have been identified in humans, as summarized in Figure S1. Of note, the terms MMP4, MMP5, MMP6, MMP18, and MMP22 are not used in humans because they correspond to MMP17, MMP24, MMP25, MMP19, and MMP27, respectively. In addition, there are two equivalent forms of MMP23 (MMP23A and MMP23B) in humans that are encoded by two distinct genes, and MMP23A is a pseudogene [17]. According to their structure and substrate specificities, MMP gene family can be classified into subgroups of collagenases (−1, −8 and −13), stromelysins (−3, −10 and −11), gelatinases (−2 and −9), matrilysins (−7 and −26), membrane-type (-14, −15, −16, −17, −23, −24 and −25), and other MMPs (−12, −19, −20, −21, −27 and −28) [18,19]. Further, a corresponding family named tissue inhibitors of metalloproteinases (TIMPs), which include four members (TIMP1 to TIMP4), are natural inhibitors of MMPs [20,21]. ECM integrity and remodeling depend on the dynamic balance between remodeling enzymes (MMPs) and their inhibitors (TIMPs) [22,23]. Likewise, studies on the expression of TIMPs in HNSCC and their roles in prognosis are limited, and their results are controversial.
Precision medicine for age-related macular degeneration: current developments and prospects
Published in Expert Review of Precision Medicine and Drug Development, 2018
Marc Biarnés, Vassil Vassilev, Everson Nogoceke, Eszter Emri, Eduardo Rodríguez-Bocanegra, Lucia Ferraro, Míriam Garcia, Sascha Fauser, Jordi Monés, Imre Lengyel, Tunde Peto
When nAMD and GA were compared, four variants showed different associations (ARMS2-HTRA1, CETP, MMP9, and SYN-TIMP3), but only MMP9 showed exclusive association with nAMD [26]. Comparison of intermediate and advanced AMD showed a significant overlap in genetic determinants (correlation of 0.78 [95% CI = 0.69–0.87]). Most of those variants were exclusively associated with nAMD, and these were related to extracellular matrix remodeling (COL15A1, COL8A1, MMP9, PCOLCE, MMP19, CTRB1-CTRB2, and ITGA7), paving the way for a theory that patients with such variants may progress rapidly to nAMD and may have maximum benefit from future genetic diagnostics and preventive treatment [26].
Heterogeneity of T cells and macrophages in chlorine-induced acute lung injury in mice using single-cell RNA sequencing
Published in Inhalation Toxicology, 2022
Chen-qian Zhao, Jiang-zheng Liu, Meng-meng Liu, Xiao-ting Ren, De-qin Kong, Jie Peng, Meng Cao, Rui Liu, Chun-xu Hai, Xiao-di Zhang
Subsequently, GSVA analysis to characterize the functions of lung six subtypes of macrophages (Figure 6(A)). Mø-1 showed gene enrichment primarily for apoptotic process and biological-process (Figure 6(A)), as evidenced by several marker genes, such as Calcrl, Gphn, and others (Figure 6(B)). Mø-2 exhibited preference for genes involved in phosphorylation, including protein phosphorylation, peptidyl-serine phosphorylation, and positive regulation of protein phosphorylation (Figure 6(A)), which was validated by several representative markers, as shown in Figure 6(C). Both Mø-1 and Mø-3 are enriched in the positive regulation of transmission of nerve impulse, neutrophil apoptotic process and regulation of vascular endothelial growth factor production (Figure 6(A,D)). It can also be seen from the heat map of the correlation between cell populations that Mø-1 and Mø-3 have strong similarities (Figure 6(H)). Mø-4 showed higher level of genes involved in a multiplicity of pathways, such as response to extracellular stimulus, proteolysis involved in cellular protein catabolic process, regulation of intracellular protein transport, etc. We particularly observed dramatic upregulation of related genes, such as Ccr1, Mmp19, Msr1, and Slc41a2, in this subcluster (Figure 6(A,E)). Interestingly, signal pathways related to cell division, cell cycle and chromosome organization are enriched in Mø-5 (Figure 6(A)). Just like the genes Iqgap3, Kif15, kif14, and TTK, KNL1 in these pathways are highly expressed in Mø-5 (Figure 6(F)). Mø-6 was found to highly express genes enriched in regulation of cell shape and the establishment of endothelial barrier, suggesting that Mø-6 may be involved in the anti-inflammatory and wound repair functions potential of M2 macrophages (Figure 6(A,G)).