Background: The impact of aberrant expression of miRNAs, small noncoding RNAs of 19 to 23 nucleotide, has been reported in different types of cancer, such as breast cancer. Authors aim to investigate the role of circulating miRNA-335 as a diagnostic and prognostic marker for breast cancer.Materials and Methods: miRNA-335 expression was measured in primary breast cancer patients (n = 106), patients with benign breast lesion (n = 49) and healthy individuals as control (n = 40) using quantitative real-time polymerase chain reaction and its diagnostic efficacy, relation with clinicopathological factors, and disease-free survival (DFS) and overall survival (OS) were assessed.Results: A significant decrease in miRNA-335 expression was reported in patients with breast cancer as compared to the other two investigated groups. The positivity rate for miRNA were related to adverse clinical features of primary breast cancer as high histological grading (X 2 = 7.72, P = 0.016), presence of metastasis to lymph node (X 2 = 21.8, P < 0.001), large tumor size (X 2 = 6.41, P = 0.041), and hormonal status (P < 0.001). miRNA-335 mean rank level was significantly different among breast cancer subtypes and its level was inferior in triple negative breast cancer. Worse DFS (X 2 = 7.76, P = 0.005) and OS (X 2 = 9.3, P = 0.002) were reported with decreased miRNA-335 level. Conclusion: Assessment of circulating miRNA expression level is a promising minimal invasive marker for diagnosis and prediction of breast cancer prognosis with significant discrepancies among molecular breast cancer subtypes. K E Y W O R D S breast cancer subtypes, clinicopathological factors, diagnosis, micro-RNA, prognosis, tumor suppressor J Cell Biochem. 2019;120:8975-8982.wileyonlinelibrary.com/journal/jcb

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These findings indicate that investigated biomarkers are constructive for early diagnosis of breast cancer and MMP-9/TIMP-1 ratio might be a new significant marker in predicting breast cancer development.

Background. Genetic aberrations and epigenetic alterations have been reported in different types of cancer. Impact of Isocitrate dehydrogenase1 (IDH1) and O6-methylguanine-DNAmethyltransferase (MGMT) in glioblastoma (GB) have been of great interest due to their implications in prediction of prognosis of several types of cancer. It was aimed to investigate the clinical role of IDH1 mutation and MGMT methylation pattern among GB patients versus non-neurooncological diseases (NND) patients and their impact on survival criteria. Methods. Formalin-Fixed Paraffin-Embedded (FFPE) tissue sections of 58 GB and 20 non-onconeurological diseases patients were recruited and IDH1 mutation were detected using Cast-PCR technology and MGMT methylation was detected using Methyl II quantitative PCR approach. Their results were assessed with other clinicopathological criteria and correlated with survival patterns (progression free survival [PFS] and overall survival [OS]). Results. IDH1 mutation was detected among 15 GB cases (15/58) and it was not reported among NND (P=0.011). Receiver operating characteristic (ROC) curve were plotted to discriminate between MGMT methylation among studied groups. Patients with MGMT methylation ≥ 66% was reported as high methylation, which was recorded significantly in 51.7% and 100% of GB cases and NND, respectively. Both showed significant difference with performance status, while MGMT methylation was significantly related with tumor size and tumor location. IDH1 mutation and MGMT methylation reported significant increase with GB patients revealed complete response to treatment. Survival pattern was better for IDH1 mutation and MGMT high methylation as compared to IDH1 wild type or MGMT low-moderate methylation, respectively and favorable survival was detected when both were combined than using either of them alone. Conclusion. Detection of IDH1 mutation and MGMT methylation among GB patients could aid in prediction of their response to treatment and their survival patterns, and their combination is better than using any of them alone.

Background. Breast cancer is among the most common female cancers worldwide according to WHO 2020 data. Breast cancer tumor suppressor genes (BRCA1 and BRCA2) are the most susceptibility genes for breast cancer. Thus, authors aimed to detect germline mutations of BRCA1 and BRCA2 genes among Egyptian female breast cancer patients. Methods. Blood samples were collected from primary breast cancer patients (n=22), benign breast lesions (n=5) and healthy control (n=7). Then DNA was extracted and germline mutational profiling of BRCA1 and BRCA2 were studied using next generation sequencer (Ion Torrent personal Genome Machine [PGM]).Results. A total of 135 genetic variations were detected, 59 in BRCA1 and 76 BRCA2, 2indels and 133 SNV, nearly 55% of those variants were missense variants, 38% were synonyms and 7% were nonsense. Ten exonic and 49 intronic variations were detected in BRCA1. The exonic variants in BRCA1were grouped as 6 ​​synonymous variants, one 3-prime UTR variant, 12 missense variants, 11 non coding transcript exon variants, 2 splice_region_variant,synonymous_variant, and 2 stop gain variants were previously reported to be pathogenic in Clinvar database. For BRCA2, 55 intronic variations and 21 exonic variants were detected, from the exonic variations there were 13 new mutations and 8 previously reported (7 were benign and only one were reported to be with conflicting pathogenicity on the clinvar database). Conclusion. This study reports gremline profiling of BRCA1 and BRCA2genetic mutations among Egyptian females with breast cancer using next generation sequencing as high throughput technology for a better coverage for mutational analysis that may benefit in clinical routine practice.