Implication By understanding Matrix Metalloprotease (MMP) dysregulation from a pan-cancer perspective, this study sheds light on the diagnostic potentials of MMPs across multiple neoplasms. Background MMPs are intriguing genes related to cancer disease progression, functional promotion of angiogenesis, invasion, metastasis, and avoidance of immune surveillance. Many studies have noted these genes are frequently upregulated in cancer. However, expression patterns of all MMPs and their diagnostic and prognostic potential have not been investigated in a pan-cancer perspective. Methods The Cancer Genome Atlas (TCGA) data were used to evaluate diagnostic and prognostic potential of 24 MMPs in fifteen different cancer types. Gene expression measured by RNA-seq was analyzed by differential expression, hierarchical clustering, and ROC analysis for individual genes and in combination. Results MMP1, MMP9 , MMP10 , MMP11 , and MMP13 were almost universally upregulated across all cancers, with significant ( p < 0.05) fold change (FC > 2) in ten of fifteen cancers. MMP3 , MMP7 , MMP12 and MMP14 ) are significantly up-regulated in at least 10 cancer types. Interestingly, MMP2 , MMP7 , MMP23B , MMP27 and MMP28 ) are significantly down-regulated in seven to nine cancer types. Multiple MMPs possess AUC’s > 0.9 in more than one cancer. However, survival analyses suggest that the prognostic value of MMPs is limited to clear cell renal carcinoma. Conclusions Most MMPs have consistently increased gene expression across cancers, while several MMPs have consistently decreased expression in several cancer types. Many MMPs have diagnostic value individually or in combination, while the prognostic value of MMPs is restricted to one subtype of kidney cancer. Electronic supplementary material The online version of this article (10.1186/s12885-019-5768-0) contains supplementary material, which is available to authorized users.

In patients with Type 2 diabetes and inadequate glucose control while on insulin or insulin and oral agent(s) combination therapy, treatment with a twice-daily insulin lispro mixture plus metformin, which targets both post-prandial and pre-meal BG, provided clinically significant improvements in A1c, significantly reduced post-prandial BG after each meal, and reduced nocturnal hypoglycaemia as compared with once-daily glargine plus metformin, a treatment that targets fasting BG.

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Background/Aims Several studies have shown that regions of hypoxia develop in the liver during chronic injury. Furthermore, it has been demonstrated that hypoxia stimulates the release of mediators from hepatic stellate cells (HSCs) that may affect the progression of fibrosis. The mechanism by which hypoxia modulates gene expression in HSCs is not known. Recent studies demonstrated that the hypoxia-activated transcription factor, hypoxia-inducible factor-1α (HIF-1α), is critical for the development of fibrosis. Accordingly, the hypothesis was tested that HIF-1α is activated in HSCs and regulates expression of genes important for HSC activation and liver fibrosis. Methods HSCs were isolated from mice and exposed to hypoxia. HIF-1α and HIF-2α activation were measured, and gene expression analyzed by gene array analysis. To identify genes regulated by HIF-1α, HSCs were isolated from Control and HIF-1α-Deficient mice. Results Exposure of primary mouse HSCs to 0.5% oxygen activated HIF-1α and HIF-2α. mRNA levels of numerous genes were increased in HSCs exposed to 0.5% oxygen, many of which are important for HSC function, angiogenesis, and collagen synthesis. Of the mRNAs increased, Ccr1, Ccr5, macrophage migration inhibitory factor, interleukin-13 receptor α1, prolyl-4-hydroxylase α2 (PHD α2) were completely HIF-1α-dependent. Upregulation of VEGF and placental growth factor were partially HIF-1α-dependent and upregulation of angiopoietin-like 4 and PHD α1 were HIF-1α-independent. Conclusions Results from these studies demonstrate that hypoxia, through activation of HIF-1α, regulates expression of genes that may alter the sensitivity of HSCs to certain activators and chemotaxins, and regulates expression of genes important for angiogenesis and collagen synthesis.

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Proteins identified in this study are implicated in signaling, glycosylation, immune response, molecular transport, and lipid metabolism. The identified candidate proteins may be potential biomarkers associated with POAG development and may lead to more insight in understanding the mechanisms underlying the pathogenesis of this disease.