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.

Involvement of FAM170B-AS1, hsa-miR-1202, and hsa-miR-146a-5p in breast cancer.

BACKGROUND: FAM170B-AS1 is usually expressed low in all organs except for testicular tissues. No study was performed to explore its role in breast cancer (BC). Contradictory results were reported about hsa-miR-1202 and hsa-miR-146a-5p in BC. OBJECTIVE: The present study aimed to explore the involvement of FAM170B-AS1 in BC using bioinformatics predictive tools, followed by a practical validation besides exploring the impact of hsa-miR-1202 and hsa-miR-146a-5p in BC. METHODS: This study enrolled 96 female patients with BC, 30 patients with benign breast diseases (BBD), and 25 control subjects. The expressions of circulating FAM170B-AS1, hsa-miR-1202, and hsa-miR-146a-5p were quantified using qRT-PCR. These ncRNAs' associations, predictive, and diagnostic roles in BC were statistically tested. The underlying miRNA/mRNA targets of FAM170B-AS1 in BC were bioinformatically predicted followed by confirmation based on the GEPIA and TCGA databases. RESULTS: The expression of FAM170B-AS1 was upregulated in sera of BC patients and hsa-miR-1202 was upregulated in sera of BBD and BC patients while that of hsa-miR-146a-5p was downregulated in BC. These FAM170B-AS1 was significantly associated with BC when compared to BBD. FAM170B-AS1 and hsa-miR-1202 were statistically associated with the BC's stage, grade, and LN metastasis. FAM170B-AS1 and hsa-miR-146a-5p gave the highest specificity and sensitivity for BC. KRAS and EGFR were predicted to be targeted by FAM170B-AS1 through interaction with hsa-miR-143-3p and hsa-miR-7-5p, respectively. Based on the TCGA database, cancer patients having mutations in FAM170B show good overall survival. CONCLUSIONS: The present study reported that for the first time, FAM170B-AS1 may be a potential risk factor, predictive, and diagnostic marker for BC. In addition, FAM170B-AS1 might be involved in BC by interacting with hsa-miR-143-3p/KRAS and hsa-miR-7-5p/EGFR through enhancement or repression that may present a new therapeutic option for BC.

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.

Long non-coding RNAs BACE1-AS and BC200 in multiple sclerosis and their relation to cognitive function: A gene expression analysis.

Cognitive impairment is a common and debilitating feature of multiple sclerosis (MS), and the dysregulation of synaptic plasticity is one of its direct causes. Long non-coding RNAs (lncRNAs) have been shown to play a role in synaptic plasticity, but their role in cognitive impairment in MS has not been fully explored. In this study, using quantitative real-time PCR, we examined the relative expression of two specific lncRNAs, BACE1-AS and BC200, in the serum of two cohorts of MS patients with and without cognitive impairment. Both lncRNAs were overexpressed in both cognitively impaired and non-cognitively impaired MS patients, with consistently higher levels in the cohort with cognitive impairment. We also found a strong positive correlation between the expression levels of these two lncRNAs. Notably, BACE1-AS was consistently higher in the remitting cases of both relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) groups than in the respective relapse cases of the same subtype, with the SPMS-Remitting group of cognitively impaired MS patients showing the highest expression of BACE1-AS among all MS groups. Additionally, we observed that the primary progressive MS (PPMS) group had the highest expression of BC200 in both cohorts of MS. Furthermore, we developed a model called Neuro_Lnc-2, which showed better diagnostic performance than either BACE1-AS or BC200 alone in predicting MS. Our findings suggest that these two lncRNAs may have a significant impact on the pathogenesis of the progressive types of MS and on the cognitive function of the patients. Future research is required to confirm these findings.

Potential diagnostic role of circulating MiRNAs in colorectal cancer.

OBJECTIVES: Colorectal cancer (CRC) is the third most common and fourth most deadly cancer worldwide despite its various screening method. Thus, the search for novel and better markers is continuous. This study aimed to assess the combined expression levels of miR-133a, miR-574-3p, and miR-27a in early diagnosis of colorectal cancer in comparison to traditional tumor markers (CEA and CA19.9). METHODS: miR-133a, miR-574-3p, and miR-27a were assessed in sera of 120 participants categorized into healthy control group (n = 20), benign group (n = 30) and malignant group (n = 70) using real-time PCR. RESULTS: miR-133a, miR-574-3p, and miR-27a expressions showed significant difference among different staging, grading and tumor size of CRC. The sensitivities of the three miRNAs whether combined or individually used were better than routinely used tumor markers (CEA and CA19.9) leading to more accurate and faster diagnosis of CRC. CONCLUSION: Synergetic detection of miRNA-133a, miRNA-574-3p, and miRNA-27a may serve as better noninvasive biomarkers with higher combined sensitivity for early diagnosis of CRC than individual detection of miRNAs.

Pomegranate juice and punicalagin-mediated chemoprevention of hepatocellular carcinogenesis via regulating miR-21 and NF-κB-p65 in a rat model.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common neoplasm among primary liver malignancies, accounting for 70%-85% of total liver cancer cases worldwide. It is also the second-leading cause of cancer-related death worldwide. Recent research has investigated naturally occurring products high in polyphenolic compounds in the regression and prevention of HCC. This study investigated the chemoprevention effects of pomegranate juice (PJ) and punicalagin (PCG) against diethylnitrosamine (DENA)-induced hepatocarcinogenesis in male albino rats. METHODS: Animals were randomized into six groups and treated for 11 weeks as follows: group 1 was a negative control group, group 2 was treated orally with 10 mL PJ per kilogram body weight (kg bw), group 3 was treated orally with 18.5 mg PCG/kg bw, and groups 4-6 were injected with an intraperitoneal dose of DENA (50 mg/kg bw) weekly beginning in the third week. Group 4 was a HCC control (DENA-treated group), group 5 was HCC + PJ, and group 6 was HCC + PCG. RESULTS: PJ antagonized DENA-induced elevations of ALAT, TNF-α, NF-κB-p65, GST, MDA, and NO and restored total protein, IL-10, SOD, and CAT levels. Moreover, PJ resulted in downregulation of miR-21, Bcl-2, and Bcl-XL and an upregulation of caspase-3 and Bax mRNA expressions. These chemoprevention effects of PJ also alleviated the hepatic preneoplastic lesions induced by DENA. Although PCG treatment induced some modulation in DENA-treated rats, it did not show potent chemoprevention activity and induced some side effects. CONCLUSION: Both of PJ and PCG downregulated miR-21 expression and triggered apoptosis. However, PJ was more effective than pure PCG in alleviating the hepatic antioxidant defense state and the inflammatory status. So, PJ was superior in prevention of DENA-induced hepatocellular carcinogenesis in rats than pure PCG.

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.

Expression of MiR-335 and its target metalloproteinase genes: clinical significance in breast cancer.

BACKGROUND: Early diagnosis of breast cancer decreases mortality rate; therefore, novel diagnostic methods are urgently required. In this study, authors aimed to investigate the role of serum-derived miR-335 in breast cancer, and the expression of matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) and evaluating their feasibility and clinical utility as biomarkers for the early detection of breast cancer. MATERIALS AND METHODS: Blood samples were collected from a total of 210 individuals who were enrolled in this study. The participants were divided into newly diagnosed breast cancer patients (n = 115), patients with benign breast lesions (n =55) and healthy individuals as control group (n =40). The expression profile of miR-335, MMP2 and MMP9 were determined using quantitative polymerase chain reaction (qPCR). RESULTS: MiR 335 expression level was down-regulated in primary breast cancer group as compared to benign breast group and healthy individuals with 98% and 94.9% sensitivity and specificity, respectively. MMP2 and MMP9 showed significantly higher expression levels in breast cancer group as compared to both benign and healthy group and reporting 92.7% and 93% sensitivity, respectively. The relations between investigated markers and pathologic types, staging, grading, and lymph node involvement were significant with these factors. Expression level of miR-335 was decreased with increased MMP2 and MMP9 at significant level. CONCLUSION: MiR-335, MMP2, and MMP9 can be used as diagnostic markers in breast cancer.

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.

Clinical role of MiRNA 29a and MiRNA 335 on breast cancer management: their relevance to MMP2 protein level.

BACKGROUND: Circulating miRNAs are novel biomarkers, authors aimed to investigate the expression level of miR-29a and miR-335 and their relevance to CEA, CA15.3, and matrix metalloproteinase-2 (MMP2). MATERIALS AND METHODS: Breast cancer (BC) patients (n = 44), benign breast lesion patients (n = 25), and healthy individuals (n = 19) were enrolled for detection of miRNA expression levels, MMP2 and biochemical markers using quantitative polymerase chain reaction (PCR) and ELISA, respectively. RESULTS: Expression of miR-29a and miR-335 were significantly decreased in breast patients as compared to healthy individuals, while biochemical markers were high in BC patients as compared to the other two groups. The diagnostic efficacy for miR-29a, miR-335, and MMP2 were superior to both CEA and CA 15.3 for early detection of BC patients. CONCLUSIONS: Detection of the miR-29a and miR335 expression levels in serum samples are significant promising biomarkers for BC diagnosis.

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.

Implications of targeted next-generation sequencing for bladder cancer: report of four cases.

BACKGROUND: Bladder cancer is considered heterogeneous diseases with two major subgroups: non-muscle- invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). It is a major healthcare problem, and it is one of the leading causes of mortality worldwide. Genetic mutations are not only a cause for carcinogenesis but are also a way for treatment strategy. The present study aimed to investigate breast cancer (BRCA genes) tumor suppressor gene mutations in bladder cancer tissue and combined blood samples for patients who developed secondary tumor after or during trimodal therapy. Fresh tissue samples and their matched blood samples were collected from four patients with bladder cancer. The objective regions for the examined genes (BRCA1 and BRCA2) were sequenced using next-generation sequencing (NGS); generated BAM files were uploaded to the cloud-based Ionreporter server, and the Oncomine BRCA-specific plugin was used to analyze the paired normal and tumor sample for each patient using the default plugin parameters. RESULTS: Intronic BRCA1 mutation c.5050-104 C >T was reported among the four investigated bladder cancer patients, and three somatic mutations were reported as follows: two of them were found to be benign rs1064793056 and rs28897679 on the Clinivar database and one nonsense pathogenic variant rs80357006. BRCA 2 gene mutation reported an exonic synonymous mutation rs397507876 in the tissue and germline DNA. Patients were treated with trimodal; however, three bladder cancer patients who reported BRCA mutations developed secondary tumors. CONCLUSION: Identification of mutational BRCA changes in bladder cancer is a promising marker for better treatment strategy. Further studies are encouraged on a large cohort of bladder cancer patients to confirm our findings.

Impact of circulating miRNA-373 on breast cancer diagnosis through targeting VEGF and cyclin D1 genes.

BACKGROUND: Breast cancer (BC) is the common primary tumor among females. Hence, there is an urgent need to improve the early prediction and diagnosis of BC. For that reason, the object of the current study is to analyze the expression levels of miRNA-373 and its target genes including vascular endothelial growth factor (VEGF) and cyclin D1 in women with BC. RESULTS: Upregulation of miRNA-373 and its target genes was observed in BC patients followed by patients with benign breast lesions compared to downregulation in controls. There was a significant association between the expression level of miRNA-373 and all clinical features. The same associations were observed between its target genes and all clinico-pathological features except hormonal status. The correlation between miRNA-373 and both genes was significant. CONCLUSIONS: Our results prove that miRNA-373, as an oncomir, would be a vital biomarker for BC diagnosis and prognosis by targeting both VEGF and cyclin D1.

Clinical impact of PTEN methylation status as a prognostic marker for breast cancer.

BACKGROUND: Aberrant DNA methylation of phosphatase and tensin homolog (PTEN) gene has been found in many cancers. The object of this study was to evaluate the clinical impact of PTEN methylation as a prognostic marker in breast cancer. The study includes 153 newly diagnosed females, and they were divided according to their clinical diagnosis into breast cancer patients (n = 112) and females with benign breast lesion (n = 41). A group of healthy individuals (n = 25) were recruited as control individuals. Breast cancer patients were categorized into early stage (0-I, n = 48) and late stage (II-III, n = 64), and graded into low grade (I-II, n = 42) and high grade (III, n = 70). Their pathological types were invasive duct carcinoma (IDC) (n = 66) and duct carcinoma in situ (DCI) (n = 46). Tumor markers (CEA and CA15.3) were detected using ELISA. DNA was taken away from the blood, and the PTEN promoter methylation level was evaluated using the EpiTect Methyl II PCR method. RESULTS: The findings revealed the superiority of PTEN methylation status as a good discriminator of the cancer group from the other two groups (benign and control) with its highest AUC and increased sensitivity (96.4%) and specificity (100%) over tumor markers (50% and 84% for CEA and 49.1% and 86.4% for CA15.3), respectively. The frequency of PTEN methylation was 96.4% of breast cancer patients and none of the benign and controls showed PTEN methylation and the means of PTEN methylation (87 ± 0.6) were significantly increased in blood samples of breast cancer group as compared to both benign and control groups (25 ± 0.7 and 12.6 ± 0.3), respectively. Methylation levels of PTEN were higher in the blood of patients with ER-positive than in patients with ER-negative cancers (P = 0.007) and in HER2 positive vs. HER2 negative tumors (P = 0.001). The Kaplan-Meier analysis recognizes PTEN methylation status as a significant forecaster of bad progression-free survival (PFS) and overall survival (OS), after 40 months follow-up. CONCLUSIONS: PETN methylation could be supposed as one of the epigenetic aspects influencing the breast cancer prognosis that might foretell more aggressive actions and worse results in breast cancer patients.

Alterations of PTEN and SMAD4 methylation in diagnosis of breast cancer: implications of methyl II PCR assay.

BACKGROUND: Diagnosis of breast cancer is more complicated due to lack of minimal invasive biomarker with sufficient precision. DNA methylation is a promising marker for cancer diagnosis. In this study, authors evaluated methylation patterns for PTEN and SMAD4 in blood samples using EpiTect Methyl II QPCR assay quantitative PCR technology. RESULTS: Methylation status for PTEN and SMAD4 were statistically significant as breast cancer patients reported hypermethylation compared to benign and control groups (77.1 ± 17.9 vs. 24.9 ± 4.5 and 15.1 ± 1.4 and 70.1 ± 14.4 vs. 28.2 ± 0.61 and 29.5 ± 3.6, respectively). ROC curve analysis revealed that both PTEN (AUC = 0.992) and SMAD4 (AUC = 0.853) had good discriminative power for differentiating BC from all non-cancer individuals (benign and healthy combined) compared to routine tumor markers CEA (AUC = 0.538) and CA15.3 (AUC = 0.686). High PTEN methylation degree was associated with late stages (84.2 ± 17.4), positive lymph node (84.2 ± 18.5), positive ER (81.3 ± 19.7), positive PgR (79.5 ± 19.1), and positive HER2 (80.7 ± 19.0) vs. 67.4 ± 13.8, 70.6 ± 14.8, 72.8 ± 14.9, 72.5 ± 14.7, and 70.2 ± 13.5 in early stages, negative lymph node, negative ER, negative PgR, and negative HER2, respectively. Similar results were obtained regarding SMAD4 methylation. Sensitivity, specificity, positive and negative predictive values, and accuracy for methylated PTEN were 100%, 95%, 99.1%, 100%, and 95%, respectively when differentiated BC from all-non cancer controls. Interestingly, PTEN could distinguish early BC stages with good sensitivity 84.4%, 51.4%, 69.1%, 72%, and 70%, respectively. CONCLUSION: Methylation status of PTEN and SMAD4 is a promising blood marker for early detection of breast cancer. Future studies are needed for their role as prognostic markers.

Clinical impact of LncRNA XIST and LncRNA NEAT1 for diagnosis of high-risk group breast cancer patients.

Long noncoding RNAs (lncRNAs) are evolving as contributing biomarkers for many diseases. Among these lncRNAs, X inactive-specific transcript (XIST), and nuclear paraspeckle assembly transcript 1 (NEAT1) were studied as undesirable upregulated nucleic acid markers for unfavorable prognosis of cancer. The authors aimed to investigate their role as diagnostic markers for breast cancer (BC) patients with high-risk factors. Serum samples were obtained from BC patients (n = 121), patients with benign breast lesions (n = 35), and healthy volunteers (n = 22). Assessment of lncRNA XIST, and lncRNA NEAT1 expression was performed using real time PCR. Expression levels of the investigated lncRNAs were significantly higher in BC patients as compared to the other groups. Both lncRNAs were significantly correlated with BC laterality, lymph node involvement, and clinical stages. LncRNA NEAT1 reported a significant aberrant expression with pathological types, histological grading and, hormonal status. The sensitivity of lncRNA NEAT1 was superior for detection of BC with high risk-factors as compared to lncRNA XIST. In conclusion, the detection of lncRNAs in body fluids has demonstrated a significant importance for detecting BC patients with high-risk factors, and was related to hormonal receptors, thus may be used for determining the direction of treatment strategy.

Serum MiRNA-27a as potential diagnostic nucleic marker for breast cancer.

BACKGROUND: Accumulating evidence reveals that microRNA 27a (miR 27a) is implicated in the pathogenesis of cancer. However, its diagnostic role in breast cancer (BC) still needs investigation. MATERIALS AND METHODS: MiR 27a expression was assessed in serum samples from patients with primary BC (n = 100), benign breast lesions (n = 30) and control group served as healthy volunteers (n = 20) using quantitative real-time PCR. RESULTS: Both expression and mean rank of miR 27a and tumor markers among BC patients as compared to the other two groups. Clinicopathological characteristics showed significant relation with miRN 27a expression for clinical stage, histological grading, ER receptor and HER-2/neu. The diagnostic efficacy for miR 27a was superior to both tumor markers for early detection of BC especially high-risk BC groups. CONCLUSION: Detection of miR 27a expression may serve as a potential sensitive minimally invasive molecular marker for early detection of primary BC.

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 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 significance of blood-based miRNAs as diagnostic and prognostic nucleic acid markers in breast cancer: Comparative to conventional tumor markers.

microRNAs (miRNAs) are implicated in carcinogenesis and their expression in biological fluids offer great potential as nucleic acid markers for cancer detection and progression. Authors investigated the expression level of miRNAs (miRNA-21, miRNA-126, and miRNA-155) to evaluate their role as diagnostic and prognostic markers for breast cancer compared with other commonly used protein-based markers (CEA and CA15-3). Serum samples from patients with breast cancer (n = 96), patients with benign breast lesion (n = 47), and healthy individuals (n = 39) were enrolled for detection of miRNA expression levels and protein-based tumor markers using fluorescent real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Correlation among investigated markers with clinicopathological factors and clinical outcomes were determined. Expression of miRNA-21 and miRNA-155 revealed significant increases in patients with breast cancer compared with both benign and control groups, the same result was reported for tumor markers; on the other hand, miRNA-126 was significantly decreased in breast cancer group as compared with the other two groups. miRNA frequencies were significantly related to clinical staging and histological grading as compared with tumor markers. Patients with breast cancer with increased miRNA-21 and miRNA-155 and decreased miRNA-126 expressions had significantly worse disease-free survival, while only miRNA-21 and miRNA-126 showed poor OS (P< 0.005). In conclusion, investigated miRNAs were superior over tumor markers for the early stage of breast cancer especially those with high-risk factor and their assessment in blood facilitates their role as a potential prognostic molecular marker.