Prognostic impact of MYD88 and TP53 mutations in diffuse large B Cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of lymphoma. It is a highly heterogeneous lymphoid neoplasm, with variations in gene expression profiles and genetic alterations. MYD88 and TP53 genes are common to be expressed and mutated in DLBCL patients with controversy regarding their role in prognosis and survival. This study aims to determine the predictive and prognostic role of MYD88 and TP53 gene mutation in DLBCL. A prospective cohort study was conducted on 50 patients who were diagnosed with DLBCL and 30 healthy individuals to assess the sensitivity and specificity of MYD88 and TP53 genetic mutations. MYD88 and TP53 gene mutations were more sensitive, specific, and accurate in predicting overall mortality and disease progression in comparison with the international prognostic index. Mutant MYD88 and TP53 showed their prognostic importance for worse objective response rates and survival outcomes. Both mutant MYD88 and TP53 were associated with worse ORR. There was a significant statistical difference for both MYD88 and TP53 with regard to 2-year PFS and 2-year OS rate. Hence, both mutant MYD88 and TP53 can be used in predicting disease progression and overall mortality.

Prognostic utility of lncRNAs (LINC00565 and LINC00641) as molecular markers in glioblastoma multiforme (GBM).

BACKGROUND AND AIM: Glioblastoma multiforme (GBM) is primary brain tumor grade IV characterized by fast cell proliferation, high mortality and morbidity and most lethal gliomas. Molecular approaches underlying its pathogenesis and progression with diagnostic and prognostic value have been an area of interest. Long-non coding RNAs (lncRNAs) aberrantly expressed in GBM have been recently studied. The aim is to investigate the clinical role of lncRNA565 and lncRNA641 in GBM patients. PATIENTS AND METHODS: Blood samples were withdrawn from 35 newly diagnosed GBM cases with 15 healthy individuals, then lncRNA565 and lncRNA641 expression were evaluated using real time-PCR. Their diagnostic efficacy was detected using receiver operating characteristic curve. Progression free survival (PFS) and overall survival (OS) were studied using Kaplan-Meier curves. RESULTS: lncRNAs expressions were increased significantly among GBM as compared to control group. Their expressions were correlated with clinico-pathological data and survival pattern for the studied GBM patients. Higher levels of both lncRNAs were correlated to worse performance status. Expression of lncRNA565 was increased with large tumor size (≥ 5 cm). Survival analysis showed that both investigated lncRNA were increased with worse PFS and OS. CONCLUSION: Expression of lncRNA565 and lncRNA641 in a liquid biopsy sample can be used as prognostic biomarker for GBM patients.

Clinical recommendations in the management of advanced prostate cancer: International Gastrointestinal, Liver and Uro-oncology (IGILUC 2019) experts.

PURPOSE: Advancements in the diagnosis and treatment of prostate cancer (PC) have rapidly progressed through the past years. Various factors should be taken into account while treating individual patients to ensure optimal and careful decision making. The purpose of this consensus review is to summarize the current practice patterns when managing patients with advanced prostate cancer (APC) as there is still a lack of or very limited evidence on its clinical management in some areas. METHODS: Pre-defined questions were shared with experts prior to the consensus session that took place in Cairo, Egypt in April 2019 during the 8th International gastrointestinal, liver and uro-oncology conference (IGILUC). Voting was based mainly on the expert opinions of the panel after a thorough discussion and review of available evidence from guidelines or best evidence available concerning the topic at hand. RESULTS: A strong consensus or unanimity was reached on 47% of the proposed questions. Notably, the panelists reached consensus on several topics based on high-level expert opinion. These findings contribute in several ways to our understanding of the management of PC and provide a basis for future recommendations. There was also a lack of consensus on other several topics, which suggests the need for further supporting data addressing these knowledge gaps. CONCLUSION: This review offers a thorough understanding of APC practice and offers insight on the various opinions shared amongst experts in the field that can serve as guidance regionally and deepens our understanding of disease management globally.

Clinical impact of circulating oncogenic MiRNA-221 and MiRNA-222 in glioblastoma multiform.

BACKGROUND AND AIM: Glioblastoma multiform (GBM); most fatal brain cancer, is incurable with molecular diversity hence identification of molecular targets that contribute to GBM tumorgenesis will be suitable for the development of diagnostic and treatment strategies. Micro-RNAs (miR); small RNA molecules, are stable in blood and play a crucial role in molecular processes in GBM. Thus it was aimed to investigate the clinical role of miR-221 and miR-222 among GBM cases as compared to healthy individuals and illustrate their role in patient's survival. MATERIALS AND METHODS: Blood samples were withdrawn from 20 GBM cases before and after treatment, a group of 20 healthy individuals were served as control. For all enrolled samples expression of miR-221 and miR-222 were detected using quantitative PCR (QPCR). Sensitivities, specificities of investigated miRs and their relation with GBM clinical characteristics and patient's outcome were analyzed using Kaplan Meir curve. RESULTS: Expression of investigated miR- 221 and -222 were significantly increased in GBM cases as compared to healthy individuals (F = 12.9, at P < 0.001, F = 28.78, at P < 0.0001, respectively) and with absolute specificity for both and 90% sensitivity for miR-221 and 85% for miR-222. Among GBM patients (n = 20), mean expression level miR-221 reported significant increase with elder GBM ( > 60 years) at F = 5.7, P = 0.028, while both miR-221 and -222 showed significant difference in performance status (ECGO) at P = 0.036 and 0.007, patients with primary lesion at P = 0.001 and 0.005, surgically treatment strategy at P < 0.001 and 0.004, respectively. Patients were grouped according to their outcomes into response (complete [CR] or partial [PR]), stable disease[SD] and progressive disease [PD], miR-221 and miR-222 showed increase expression with PD and patients with worse PFS and OS were those with high miRs expression. CONCLUSION: Detection of circulating miR-221 and miR-222 may be used as circulating molecular marker for diagnosis and prediction of outcome for patients with GBM. Further studies with large cohort of samples are encouraged.

Clinical role of NDRG2-based methylation status on survival pattern of glioblastoma.

OBJECTIVES: Gliobalstoma is the most common primary brain tumor in adults with an extensive genetic and transcriptional heterogeneity, still identification of the role of DNA methylation, as one of epigenetic alterations, is emerged. Authors aimed to study the clinical role of N-myc downstream-regulated gene 2 (NDRG2) -based methylation among GBM patients versus benign neurological diseases (BND), investigate its prognostic role and its relation with survival outcomes. METHODS: A total of 78 FFPE specimens were recruited as follows: GBM (n = 58) and BND (n = 20) then analyzed for NDRG2 methylation using Methyl II quantitative PCR system. The sensitivity and specificity of methylation was detected using receiver operating characteristic (ROC) curve and the relation with clinicopathological criteria for GBM and response to treatment were studied. Survival patterns; progression free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier analyses. RESULTS: Mean methylation NDRG2 level was significantly increased in GBM patients as compared to BND and its sensitivity and specificity were 96.55% and 95%, respectively with area under curve (AUC) equals 0.973. Among the clinical characteristic factors, mean methylation level reported significant difference with ECOG and tumor site. Survival out comes revealed that NDRG2 methylation increased with worse PFS and OS at significant level (long rank test X2 = 13.3, p < .0001; and X2 = 7.1, p = .008, respectively). CONCLUSION: Current findings highlight the importance of studying DNA methylation of NDRG2 as a key factor to understand the role of epigenetic alterations in GBM.

Next generation sequencing of BRCA genes in glioblastoma multiform Egyptian patients: a pilot study.

BACKGROUND: Germ line mutations of BRCA1 and BRCA2 were correlated with a variety of cancer Authors aimed to use next-generation sequencing (NGS) to detect BRCA1 and BRCA2 germ line mutations in glioblastoma multiform (GBM) Egyptian patients. MATERIALS AND METHODS: Genomic DNA was extracted from six GBM cases, amplified using Ion AmpliSeq BRCA1 and BRCA2 panel. DNA libraries were pooled, barcoded and finally sequenced using Ion Torrent Personal Genome Machine sequencer. RESULTS: BRCA1 the previously reported rs1799966, rs1799950, rs16941 were found in five cases and they are in a linkage disequilibrium forming two distinct haplotypes, which might support their role in cancer predisposition. Out of the 18 reported variants in BRCA2, three denovo mutations were detected which leads to frame shift. CONCLUSION: Further studies on large number of GBM patients and control cases to determine BRCA1 and BRCA2 germline mutations and haplotypes; diagnostic and prognostic role are encouraged.

Relevance of circulating MiRNA-21 and MiRNA-181 in prediction of glioblastoma multiforme prognosis.

BACKGROUND: Authors aimed to investigate the clinical role of miR-21 and miR-181 among glioblastoma multiforme (GBM) patients. MATERIALS AND METHODS: Expression for both miRs were detected in blood samples from newly diagnosed twenty GBM patients before and after treatment along with 20 healthy individuals using QPCR technology. RESULTS: MiR-21 reported increase expression while miR-181 reported decreased expression in GBM patients. Expression of miR-21 was up-regulated in GBM patients older than 60 years and frontal mass with tumor size > 5 cm while miR-181 expression was down-regulated among them. Worse PFS and OS reported increase in miR-21 expression and decrease in miR-181 expression. CONCLUSION: Detection of miR-21 and miR-181 expression levels may be a potential diagnostic and predictors for GBM prognosis.

Emerging role of miRNAs as liquid biopsy markers for prediction of glioblastoma multiforme prognosis.

Serum miRNAs (miRs) have gained consideration as encouraging molecular markers for cancer diagnosis and prediction of prognosis. The authors aimed to identify the exact role of miR-17-5p, miR-125b, and miR-221 among glioblastoma multiforme (GBM) patients before and after standard treatment, and correlate their expression with survival pattern. The study included 25 GBM patients and 20 healthy controls. Serum miR-17-5p, miR-125b, and miR-221 expression were analyzed before and after treatment using quantitative real-time polymerase chain reaction (qPCR). The diagnostic efficacy for the tested miRs was evaluated using the receiver operating characteristic (ROC) curve, and the relation of miRs expression versus clinical criteria for GBM was assessed. Patients' survival patterns were examined versus miRs expression levels. A significant difference was reported between miRs expression among the enrolled individuals. Both miR-17-5p and miR-221 reported significant elevations in GBM patients who: are above 60 years old, underwent biopsy resection, have a non-frontal lesion, with tumor size above 5 cm, and with performance status equals 2 according to the Eastern Cooperative Oncology Group (ECOG) Performance Status. With regard to miR-125b, a significant difference was detected according to surgery strategy, primary lesion of the tumor, and ECOG status. MiRs levels were significantly decreased for GBM patients after treatment. Survival patterns demonstrated an increase in miR-17-5p, miR-125b, and miR-221 in GBM patients with worse progression-free survival and among those with worse overall survival. Detection of serum miR-17-5p, miR-125b, and miR-221 aids in the prediction of prognosis and response to treatment strategy for GBM patients.

Clinical Significance of Serum IL-12 Level in Patients with Early Breast Carcinoma and Its Correlation with Other Tumor Markers.

AIM: To investigate the diagnostic significance of Interleukin 12 (IL-12) in breast cancer (BC) and its correlation with other tumor markers including cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and MMP9/TIMP1 ratio. METHODS: Serum levels of IL-12, tumor markers, and hormone receptors were measured in 92 BC and 56 benign lesion patients versus 40 healthy subjects. Clinical stage, tumor size, lymph node metastasis, grade, and histological type were recorded. RESULTS: BC patients have lower IL-12, but higher CA 15.3 and CEA than control group. High levels of serum IL-12 were associated with lymph node positivity and progesterone receptor negativity. IL-12 was significant lower in invasive ductal carcinoma (IDC) compared to non IDC histological type. IL-12 was higher in patients with higher stage and grade but the difference was not statistically significant. IL-12 correlates negatively with MMP9/TIMP1 ratio. CONCLUSION: IL-12 is less specific than CEA for screening early BC, but its correlation with tumor aggressiveness and progression markers may have a prognostic value.