Risk of Malignancy Following Radiofrequency Ablation of Thyroid Nodules

Radiofrequency ablation (RFA) is a safe and effective treatment of symptomatic benign thyroid nodules. However, some publications have cautioned against the use of RFA in Bethesda III, IV, and V thyroid nodules due to risk of developing follicular thyroid cancer. Unfortunately, these studies lack in statistical power due to small sample size. We aim to investigate the pathological changes following RFA of Bethesda III, IV, and V thyroid nodules. Patients treated by RFA with pre-operative and post-operative fine needle aspiration (FNA) were included. Nondiagnostic nodules were subsequently subjected to ThyGeNEXT and ThyraMIR testing. The FNA results following RFA were compared against the two FNA biopsies prior to ablation. The repeat FNA occurred between 1 and 24 months after ablation. Surgery was offered to patients when indicated and final pathology was recorded. A total of 74 thyroid nodules were included. At baseline, 21 nodules were nondiagnostic, 37 nodules were benign, and 16 nodules were either Bethesda III, IV, or V. Of the 37 benign nodules, 35 (94.6%) remained benign on repeat FNA and 2 (5.4%) became nondiagnostic with no mutation detected following molecular and genetic testing. Of the 21 baseline nondiagnostic nodules which were proven benign by ThyGeNEXT and ThyraMIR prior to ablation, 17 (81%) were benign on repeat FNA and 4 (19%) remained nondiagnostic with no mutation detected. Of the 16 Bethesda III, IV, and V nodules, 6 (37.5%) were benign on repeat FNA, 1 (6.3%) was nondiagnostic on repeat FNA, and 9 (56.2%) remained Bethesda III, IV, and V nodules with no mutation detected on molecular and genetic testing. Among the 5 patients with Bethesda III, IV, and V nodules who had surgery, 4 (80%) were benign and 1 (20%) was papillary thyroid carcinoma on surgical pathology. No patients had follicular carcinoma. Following RFA, the majority of nodules (98.6%) were benign by FNA or surgical pathology. RFA does not increase the risk of follicular carcinoma in Bethesda III, IV, and V thyroid nodules

Catching the driver mutations in Ewing sarcoma tumours: an in silico genomic analysis

OBJECTIVE: Ewing sarcoma (EWS) is a rare neuroectodermal-related malignancy affecting bones and soft tissues. The well-known hallmark of genomic alteration in EWS is gene fusion involving the Ewing Sarcoma Breakpoint Region 1 (EWSR1) gene. However, studies have determined that this is not the sole determinant of tumour transformation and indicated the presence of other mutated genes related to signalling pathways and chromatin-modifying genes. MATERIALS AND METHODS: This is an in silico analysis of the previously published genomic sequencing of 218 EWS patients and 11 cell lines. RESULTS: The presence of frequent deleterious mutations in EWSR1 (17%); titin, TTN (16%); stromal antigen 2, STAG2 (14%); and tumour protein P53, TP53 (9%) was determined. An increased prevalence of the co-occurrence of a few mutated driver genes across tumour samples was significantly noted, namely, between TP53 and either EWSR1 or STAG2 and between TTN and complement C3b/C4b receptor 1 (CR1) or zinc finger homeobox 3 (ZFHX3), suggesting their joint contribution to EWS tumour development. Patients carrying the TP53 aberration alone or combined with EWSR1 or STAG2 alterations had much lower survival rates. Functional enrichment analysis highlighted transcription factors, kinases, and hub proteins that could be putative therapeutic targets for EWS in the future. CONCLUSIONS: The current analysis provides new insights that can be used as a roadmap for future in vitro or in vivo work. A systems biology approach will be required that takes into account the genomic and epigenomic landscapes of EWS for risk stratification and future molecular targeted therapy

Long Non-Coding RNAs ANRIL and HOTAIR Upregulation is Associated with Survival in Neonates with Sepsis in a Neonatal Intensive Care Unit

Nouran B AbdAllah,1 Essam Al Ageeli,2 Abdullah Shbeer,3 Jawaher A Abdulhakim,4 Eman A Toraih,5,6 Doaa O Salman,6 Manal S Fawzy,7,8 Sanaa S Nassar1 1Department of Pediatrics, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 2Department of Clinical Biochemistry (Medical Genetics), Faculty of Medicine, Jazan University, Jazan, Saudi Arabia; 3Anesthesiology and Intensive Care, Department of Surgery, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia; 4Medical Laboratory Department, College of Applied Medical Sciences, Taibah University, Yanbu, Saudi Arabia; 5Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, USA; 6Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 7Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 8Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi ArabiaCorrespondence: Manal S Fawzy, Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt, Email [email protected] Eman A Toraih, Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, USA, Email [email protected]: Recently, long non-coding RNAs (lncRNAs) have emerged as potential molecular biomarkers for sepsis. We aimed to profile the expression signature of three inflammation-related lncRNAs, MALAT1, ANRIL, and HHOTAIR, in the plasma of neonates with sepsis and correlate these signatures with the phenotype.Patients and Methods: This case–control study included 124 neonates with sepsis (88 survivors/36 non-survivors) admitted to the neonatal ICU and 17 healthy neonates. The relative expressions were quantified by real-time PCR and correlated to the clinic-laboratory data.Results: The three circulating lncRNAs were upregulated in the cases; the median levels were MALAT1 (median = 1.71, IQR: − 0.5 to 3.27), ANRIL (median = 1.09, IQR: 0.89 to 1.30), and HOTAIR (median = 1.83, IQR: 1.44 to 2.41). Co-expression analysis showed that the three studied lncRNAs were directly correlated (all p-values < 0.001). Overall and stratification by sex analyses revealed significantly higher levels of the three lncRNAs in non-survivors compared to the survivor group (all p-values < 0.001). Principal component analysis showed a clear demarcation between the two study cohorts in males and females. Cohorts with upregulated ANRIL (hazard ratio; HR = 4.21, 95% CI = 1.15– 10.4, p=0.030) and HOTAIR (HR = 2.49, 95% CI = 1.02– 6.05, p=0.044) were at a higher risk of mortality.Conclusion: Circulatory MALAT1, ANRIL, and HOTAIR were upregulated in neonatal sepsis, and the latter two may have the potential as prognostic biomarkers for survival in neonatal sepsis.Keywords: neonatal sepsis, long non-coding RNAs, MALAT1, ANRIL, HOTAIR, surviva

Association of Angio-LncRNAs MIAT rs1061540/MALAT1 rs3200401 Molecular Variants with Gensini Score in Coronary Artery Disease Patients Undergoing Angiography

Long non-coding RNAs (lncRNAs) have emerged as essential biomolecules with variable diagnostic and/or prognostic utility in several diseases, including coronary artery disease (CAD). We aimed for the first time to investigate the potential association of five angiogenesis-related lncRNAs (PUNISHER, SENCR, MIAT, MALAT1, and GATA6-AS) variants with CAD susceptibility and/or severity. TaqMan Real-Time genotyping for PUNISHER rs12318065A/C, SENCR rs12420823C/T, MIAT rs1061540C/T, MALAT1 rs3200401T/C, and GATA6-AS1 rs73390820A/G were run on the extracted genomic DNA from 100 unrelated patients with stable CAD undergoing diagnostic coronary angiography and from 100 controls. After adjusting covariates, the studied variants showed no association with disease susceptibility; however, MIAT*T/T genotype was associated with a more severe Gensini score. In contrast, MALAT1*T/C heterozygosity was associated with a lower score. The lipid profile, and to a lesser extent smoking status, male sex, weight, hypertension, and MALAT1 (T &gt; C) (negative correlation), explained the variance between patients/control groups via a principal component analysis. Incorporating the principal components into a logistic regression model to predict CAD yielded a 0.92 AUC. In conclusion: MIAT rs1061540 and MALAT1 rs3200401 variants were associated with CAD severity and Gensini score in the present sample of the Egyptian population. Further large multi-center and functional analyses are needed to confirm the results and identify the underlying molecular mechanisms