Browsing by Author "Hadizadeh, M."

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    The Differential DNA Hypermethylation Patterns of microRNA-137 and microRNA-342 Locus in Early Colorectal Lesions and Tumours.
    (MDPI, 2019-09-21) Kashani, E.; Hadizadeh, M.; Chaleshi, V.; Mirfakhraie, R.; Young, Christopher N. J.; Irani, S.; Asadzadeh Aghdaei, H.; Ashrafian Bonab, M.
    Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, representing 13% of all cancers. The role of epigenetics in cancer diagnosis and prognosis is well established. MicroRNAs in particular influence numerous cancer associated processes including apoptosis, proliferation, differentiation, cell-cycle controls, migration/invasion and metabolism. MiRNAs-137 and 342 are exon- and intron-embedded, respectively, acting as tumour-suppressive microRNA via hypermethylation events. Levels of miRNAs 137 and 342 have been investigated here as potential prognostic markers for colorectal cancer patients. The methylation status of miRNA-137 and miRNA-342 was evaluated using methylation-specific (MSP) polymerase chain reaction (PCR) on freshly frozen tissue derived from 51 polyps, 8 tumours and 14 normal colon mucosa specimens. Methylation status of miRNA-137 and miRNA-342 was significantly higher in tumour lesions compared to normal adjacent mucosa. Surprisingly, the methylation frequency of miR-342 (76.3%) among colorectal cancer patients was significantly higher compared to miR-137 (18.6%). Furthermore, normal tissues, adjacent to the lesions (N-Cs), displayed no observable methylation for miRNA-137, whereas 27.2% of these N-Cs showed miRNA-342 hypermethylation. MiRNA-137 hypermethylation was significantly higher in male patients and miR-342 hypermethylation correlated with patient age. Methylation status of miRNA-137 and miRNA-342 has both diagnostic and prognostic value in CRC prediction and prevention.
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    GJA4/connexin 37 mutations correlate with secondary lymphedema following surgery in breast cancer patients
    (2018-02-22) Hadizadeh, M.; Ardebili, S.M.M.; Salehi, M.; Young, Christopher N. J.; Mokarian, F.; McClellan, J.; Xu, Q.; Kazemi, M.; Moazam, E.; Mahaki, B.; Bonab, Maziar Ashrafian
    Lymphedema is a condition resulting from mutations in various genes essential for lymphatic development and function which leads to obstruction of the lymphatic system. Secondary Lymphedema is a progressive and incurable condition, most often manifesting after surgery for breast cancer. Although its causation appears complex, various lines of evidence indicate genetic predisposition may play a role. Previous studies show that mutations in Connexin 47 are associated with secondary lymphedema. We have tested the hypothesis that connexin 37 gene mutations in humans are associated with secondary lymphedema following breast cancer surgery. 2211 breast cancer patients were screened and tested for reference single nucleotide polymorphisms of the GJA4 gene. The results presented in this paper indicate that two SNPs in the 3’ UTR of the GJA4 gene are associated with increased risk of secondary lymphedema in patients undergoing breast cancer treatment. Our results provide evidence of a novel genetic biomarker for assessing predisposition to secondary lymphedema in human breast cancer patients. Testing for the condition-associated alleles described here could assist and inform treatment and post-operative care plans of breast cancer patients, with potentially positive outcomes for the management of disease progression.