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A disease's aetiology is often complex, including both hereditary and environmental influences. Medical (by facilitating medication development and tailored treatment) and scientific (by illuminating the mechanical and evolutionary components of disease) goals are served by the discovery of major genetic components. A number of genetic approaches have established associations between diseases and specific regions of the genome. These include association studies and linkage analysis, which map the correlation between alleles at distinct loci and unite sites that tend to be inherited together. Studies of this kind look at hundreds of genes, which is much too many to test experimentally for possible disease codes. It follows that computational approaches for determining whether or not certain genes within a given chromosomal region may encode disease genes are very beneficial. There is a significant amount of evidence showing that many illnesses are susceptible. variances in the rates of gene expression among different kinds of cells. In particular, a gene's involvement in disease is likely to be supported by the fact that it is more prevalent in sick individuals compared to healthy ones. To identify the variations in expression levels, microarray experiments were the most common. [ABSTRACT FROM AUTHOR]

Introduction: The serum metabolomics approach has been used to identify metabolite biomarkers that can diagnose colorectal cancer (CRC) accurately and specifically. However, the biomarkers identified differ between studies suggesting that more studies need to be performed to understand the influence of genetic and environmental factors. Therefore, this study aimed to identify biomarkers and affected metabolic pathways in Malaysian CRC patients. Methods: Serum from 50 healthy controls and 50 CRC patients were collected at UKM Medical Centre. The samples were deproteinized with acetonitrile and untargeted metabolomics profile determined using liquid chromatographyquadrupole time-of-flight mass spectrometry (LC-QTOFMS, Agilent USA). The data were analysed using Mass Profiler Professional (Agilent, USA) software. The panel of biomarkers determined were then used to identify CRC from a new set of 20 matched samples. Results: Eleven differential metabolites were identified whose levels were significantly different between CRC patients compared to normal controls. Based on the analysis of the area under the curve, 7 of these metabolites showed high sensitivity and specificity as biomarkers. The use of the 11 metabolites on a new set of samples was able to differentiate CRC from normal samples with 80% accuracy. These metabolites were hypoxanthine, acetylcarnitine, xanthine, uric acid, tyrosine, methionine, lysoPC, lysoPE, citric acid, 5-oxoproline, and pipercolic acid. The data also showed that the most perturbed pathways in CRC were purine, catecholamine, and amino acid metabolisms. Conclusion: Serum metabolomics profiling can be used to identify distinguishing biomarkers for CRC as well as to further our knowledge of its pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most prevalent malignant cancer types worldwide. Although the purine metabolism pathway is vital for cancer cell survival, little is known about the role of equilibrative nucleoside transporter 2 (ENT2) in CRC development and its association with purine metabolites. The aim of the present study was to evaluate the levels of hypoxanthine phosphoribosyl transferase (HPRT), hypoxanthine and uric acid (UA), as well as xanthine oxidase (XO) activity, and investigate their association with ENT2 expression levels in a normal human colon cell line and CRC cell lines derived from different stages of CRC. These analyses were performed using the normal colon CCD-841CoN cell line and a panel of human CRC cell lines comprising SW480, HCT15 and HCT116, which represent Dukes' B, C and D stages, respectively. Reverse transcription-quantitative PCR was performed to determine the level of ENT2 mRNA expression. In cells of all CRC stages, the levels of HPRT and hypoxanthine were significantly higher (P<0.05), while XO activity and UA levels were significantly decreased (P<0.05), compared with those in the CCD-841CoN cell line. ENT2 expression was found to be elevated in cells derived from all stages of CRC. The Dukes' D stage cell line had higher levels of HPRT and hypoxanthine, although its ENT2 level was not significantly lower than that of the Dukes' B and C stage cell lines. Increased levels of HPRT and hypoxanthine in various stages of CRC may indicate an increase in the activity of the salvage pathway. The increased expression of ENT2 implies the importance of the ENT2 protein in facilitating hypoxanthine transport, which is required for enhanced DNA synthesis via hypoxanthine recycling. In conclusion, ENT2 may have potential as a target in the development of CRC therapeutics. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancer (CRC) remains the third common cancer occurred globally and the second leading cause of cancer mortality in the world. Purines are essential components of nucleotides in cell proliferation, hence altered purine metabolism has been linked to cancer growth. Increasing evidence have reported that equilibrative nucleoside transporter 2 (ENT2), a bidirectional transporter, mediates the uptake of purine nucleosides and other nucleobases. Hence, this study aims to determine the level of the rate-limiting enzymes and metabolites involved in the purine catabolism pathway and to relate the findings with the ENT2 expression level in different colorectal cancer stages. Methods: Xanthine oxidase (XO), hypoxanthine/xanthine and uric acid (UA) levels were measured in a panel of human CRC cell lines; SW480, HCT15 and HCT116, representing different CRC stages; Dukes’ B, C, and D, respectively, and were compared to normal colon cell line; CCD-841CoN. RTq-PCR was performed to determine the level of ENT2 gene expression. Results: XO enzyme activity and UA levels were significantly decreased (p<0.05) in CRC cell lines compared to the normal cells. In contrast, hypoxanthine/xanthine concentrations and ENT2 expression were significantly higher (p<0.05) in all CRC cell lines as compared to normal cells. Hypoxanthine/xanthine concentration was 0.07, 0.096 and 0.12 μM in Dukes’ B, C, and D stages of CRC. ENT2 expression level was 186, 471, and 123-fold higher in Dukes’ B, C, and D stages of CRC, respectively. HCT116 (Dukes’ D) showed the highest level of hypoxanthine/xanthine and the lowest level of ENT2 compared to other CRC stages. Conclusion: ENT2 is suggested to mediate the influx of hypoxanthine as indicated by the reduced XO activity and UA levels in CRC cells. Our findings implied that hypoxanthine may have a prognostic importance during CRC development. Further investigation is warranted to determine the role of ENT2 in CRC progression. [ABSTRACT FROM AUTHOR]