<abstract><sec> <title>Objective</title> <p>The aim of the current study was to explore the gene enrichment and dysregulated pathways on the basis of interaction network analysis of <italic>SLC30A8</italic> in type 1 diabetes mellitus (T1DM). <italic>SLC30A8</italic> polymorphism could be characterized as a beneficial tool to identify the interacting gene in developing T1DM.</p> </sec><sec> <title>Materials and methods</title> <p><italic>SLC30A8</italic> interacting protein interaction network was obtained by String Interaction network Version 11.0. Ten proteins were identified interacting with <italic>SLC30A8</italic> and were analysed by protein-protein interaction and enrichment network analysis along with Functional Enrichment analysis tool (FunRich 3.1.3) to map the gene data sets. In entire analysis, FunRich database was used as background against all annotated gene/protein list. Protein-protein interaction (PPI) and enrichment network analysis of the selected protein: <italic>SLC30A8</italic> gene along with gene mapping and pathway enrichment were performed using FunRich 3.1.3 and String Interaction network Version 11.0.</p> </sec><sec> <title>Results</title> <p>Biological pathway grouping displayed enriched proteins in TRAIL signalling pathway (<italic>p</italic> < 0.001). <italic>PTPRN, GAD2</italic> and <italic>TCF7L2</italic> were enriched in TRAIL Signalling pathway when <italic>INS</italic> was made focused gene and directly interacting with <italic>SLC30A8</italic>.</p> </sec><sec> <title>Conclusions</title> <p>TRAIL signalling pathways were enriched in T1DM. Therefore, <italic>SLC30A8</italic> along with <italic>PTPRN, GAD2</italic> and <italic>TCF7L2</italic> involved in TRAIL pathway must be further explored to understand their in vivo role in T1DM.</p> </sec></abstract>
Tissue biopsy, until date, is a gold standard for tumor diagnosis, grading, treatment, and detecting genetic evidences for identifying appropriate personalized treatments. However, it is painful, invasive, expensive, and risky making sequential biopsies basically impractical. Detection of Kras genes through liquid biopsy is the growing theragnostic technique, which is more sensitive, specific, much cost-effective and quick method for detecting the mutational status of cancers. Liquid biopsy detects biomarkers present in various body fluids, such as plasma, urine, saliva and cerebrospinal fluid, harboring cancer degraded fragments and cells shed by carcinoma such as circulating tumor cells, microRNA and circulating tumor DNA. It can be utilized as a pre-screening test for initial stage cancers also where multiple sampling is required for monitoring cancer therapies. Kras is the most extensively mutated cancer oncogene involve in altering the downstream signaling pathways, increasing oncogenic signaling, which is typically associated with poor prognosis and resistance to therapy. This review was conducted to clarify its prognostic significance as well as its mutational role in different carcinomas. To identify studies related to Kras mutation Medline, PubMed, Google Scholar and Web of Science search engines were explored and forty two relevant researches were finalized from year 2005 to 2019.
Background: To determine KRAS gene in circulating tumor DNA in comparison with histological grading through liquid biopsy in colorectal cancer patients. Methods: This dual-centered cross-sectional study included 73 diagnosed patients of colorectal cancer at different grading levels [Grade I, well differentiated (n = 7, 9.5%); Grade II, moderately differentiated (n = 14,18.9%); and Grade III, poorly differentiated (n = 52, 70%)]. Blood was collected, and plasma was separated. ctDNA was extracted, using magnetic bead-based technique (MagMAX Cell-Free DNA kit). KRAS gene was quantified through qPCR. STRING database was used to find KRAS interactomes. Results: Mean threshold cycle (CT value) of KRAS gene in Grade III samples showed significantly higher (P = 0.001) levels of ctDNA (2.7 ± 1.14) compared with Grade II and Grade I (3.1 ± 0.68, 2.3 ± 0.60), respectively. Grading characterization showed that rectal cancer (n = 22, 42.3%) with Grade III (68.8%) was more prevalent than colon and sigmoid cancer (n = 19, 36.5%, n = 11, 21%, respectively). STRING database showed 10 functional genes interacting with KRAS expressed as gene/proteins. Conclusion: Liquid biopsy can be used to detect ctDNA in plasma of CRC patients and enabled to detect the KRAS gene by qPCR. The technique being less invasive and cost-effective is convenient for multiple biopsies in different cancers.
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