Expression of Plasma miRNA-221 in Colorectal Carcinoma Patients and its Diagnostic Significance in Comparison with p53 Expression.

BACKGROUND: Colorectal carcinoma development progresses through a sequence of normal mucosa-polyp-carcinoma. Early detection of premalignancy is crucial for improved outcomes. We evaluated the diagnostic performance of plasma miRNA-221 and its feasibility in discriminating premalignant from malignant neoplasms and correlating it with immunohistochemical p53 expression. METHODS: A total of 109 plasma samples were collected (76 carcinoma, 14 premalignant, and 19 controls). MiRNA221 was quantified by qPCR for calculation of ∆Ct using RNU6B as endogenous control. p53 immunohistochemical staining was performed on corresponding tissue. RESULTS: Plasma miRNA-221 and p53 in tissues were significantly overexpressed in the malignant group when compared with the premalignant and control groups. Plasma miRNA-221 was increased in late-stage tumors with nodal or distant metastasis. ROC curve construction for distinguishing between malignant and premalignant tumors revealed a cutoff value of 2.97 with 74% sensitivity, 79% specificity, 73.7% positive predictive value and 78.6% negative predictive value (AUC = 0.824; p = 0.001). Plasma miRNA-221 significantly correlated with p53 in cancer samples (r = 0.507). CONCLUSIONS: MiRNA-221 could have a diagnostic role in differentiating malignant from premalignant neoplasms and could also serve as a predictive marker indicating tumor progression.

miRNAs role in bladder cancer pathogenesis and targeted therapy: Signaling pathways interplay - A review.

Bladder cancer (BC) is the 11th most popular cancer in females and 4th in males. A lot of efforts have been exerted to improve BC patients' care. Besides, new approaches have been developed to enhance the efficiency of BC diagnosis, prognosis, therapeutics, and monitoring. MicroRNAs (miRNAs, miRs) are small chain nucleic acids that can regulate wide networks of cellular events. They can inhibit or degrade their target protein-encoding genes. The miRNAs are either downregulated or upregulated in BC due to epigenetic alterations or biogenesis machinery abnormalities. In BC, dysregulation of miRNAs is associated with cell cycle arrest, apoptosis, proliferation, metastasis, treatment resistance, and other activities. A variety of miRNAs have been related to tumor kind, stage, or patient survival. Besides, although new approaches for using miRNAs in the diagnosis, prognosis, and treatment of BC have been developed, it still needs further investigations. In the next words, we illustrate the recent advances in the role of miRNAs in BC aspects. They include the role of miRNAs in BC pathogenesis and therapy. Besides, the clinical applications of miRNAs in BC diagnosis, prognosis, and treatment are also discussed.

Evaluation of microRNA 92a Expression and Its Target Protein Bim in Colorectal Cancer.

BACKGROUND: Colorectal cancer is one of the most commonly diagnosed cancers and leading causes of malignancy-related deaths all over the world. MicroRNAs (miRNAs) can regulate more than 60% of human genes, including tumor-stimulating, and -suppressor genes. Therefore, they can promote cancer development and affect risk of malignancy. miR-92a overexpression in CRC enhances tumor proliferation, invasion, and metastasis through downregulating different pro-apoptosis proteins including Bim. This study aimed to assess the role of plasma miR-92a as non-invasive marker in CRC patients, outline correlation between plasma miR-92a and serum Bim, and determine their correlations with clinicopathological parameters in CRC and adenoma patients. METHODS: A total of 54 newly diagnosed CRC patients, 15 colonic adenoma patients, and 15 age- and sex-matched control subjects were recruited in this study. Plasma miR-92a was assayed by TaqMan qRT-PCR and serum Bim was measured by ELISA. RESULTS: Statistically significant overexpression of serum miR-92a was observed in CRC patients as compared to adenoma and control groups (p<0.001 each) and lower serum Bim in CRC patients as compared to adenoma and control groups (p=0.001, p <0.001 respectively). The ROC curve analysis showed excellent AUC for plasma miR-92a in discriminating CRC from control (AUC=0.994), and adenoma (AUC=0.993) groups with highest diagnostic performance in discriminating CRC from controls (at cutoff 1.43, sensitivity 98.1%, specificity 93.9%), and adenoma patients (at cutoff 1.78, sensitivity 92.6%,  specificity 93.3%). The diagnostic performance in discriminating early from late CRC was good (at cutoff 15, AUC=0.641, sensitivity 61.2%, specificity 80%). A significant negative correlation was evident between plasma miR-92a and serum Bim both in adenoma and CRC groups (P<0.001 for both). Higher plasma miR-92a expression (r=0.275, p=0.044) and lower serum Bim (r=-0.299, p=0.028) were found to be correlated with late CRC stages. CONCLUSION: Circulating miR-92a and Bim could be promising, non-invasive diagnostic and prognostic biomarkers in CRC.
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Micro RNA-148a Targets Bcl-2 in Patients with Non-Small Cell Lung Cancer.

OBJECTIVE: Lung cancer is one of the most prevalent cancers and the leading cause of cancer-related deaths worldwide. MicroRNAs regulate more than 60% of human genes, including tumor suppressor genes and oncogenes. Accordingly, they can affect cancer risk. This study aimed to evaluate the role of serum miR-148a as a non-invasive biomarker in non-small cell lung cancer (NSCLC) patients and to assess the correlation between miR-148a and Bcl-2, as one of its target proteins. MATERIALS AND METHODS: A total of 50 newly diagnosed NSCLC cases and 30 apparently healthy controls were recruited in this study. MiR-148a level was measured by TaqMan- Real time RT-PCR assay and Bcl-2 level was measured by ELISA. RESULTS: Significant lower expression of serum miR-148a and higher serum Bcl-2 levels were observed in NSCLC patients as compared to the control group (p.

Competitive Endogenous Role of the LINC00511/miR-185-3p Axis and miR-301a-3p From Liquid Biopsy as Molecular Markers for Breast Cancer Diagnosis.

Breast cancer (BC) is the leading cause of female cancer-related mortalities. Evidence has illustrated the role of long non-coding RNAs (lncRNA) and microRNAs (miRNA) as promising pool of protein non-coding regulators, for tuning the aggressiveness of several malignancies. This research aims to unravel the expression pattern and the emphases of the diagnostic value of the long intergenic ncRNA00511 (LINC00511) and its downstream microRNA (miR-185-3p) and the pathogenic significance of the onco-miR-301a-3p in naïve BC patients. LINC00511 was chosen and validated, and its molecular binding was confirmed using bioinformatics. LINC00511 was measured in 25 controls and 70 patients using qPCR. The association between the investigated ncRNA's expression and the BC patients' clinicopathological features was assessed. Receiver operating characteristic (ROC) curve was blotted to weigh out their diagnostic efficacy over the classical tumor markers (TMs). Bioinformatics and Spearman correlation were used to predict the interaction between LINC00511, miR-185-3p, and miR-301a-3p altogether to patients' features. LINC00511 and miR-301a-3p, in BC patients' blood, were overexpressed, and their median levels increased significantly, while miR-185-3p was, in contrast, downregulated, being decreased fourfold. LINC00511 was elevated in BC early stages, when compared to late stages (p < 0.0003). LINC00511, miR-185-3p, and miR-301a-3p showed AUC superior to classical TMs, allowing us to conclude that the investigated ncRNAs, in BC patients' liquid biopsy, are novel diagnostic molecular biomarker signatures. Lymph node metastasis (LNM) and advanced tumor grade were directly correlated with LINC00511 significantly. Additionally, both LINC00511 and miR-301a-3p were positively correlated with the aggressiveness of BC, as manifested in patients with larger tumors (>2 cm) at (p < 0.001). Therefore, these findings aid our understanding of BC pathogenesis, in the clinical setting, being related in part to the LINC00511/miR axis, which could be a future potential therapeutic target.

Association of serum level of vitamin D and VDR polymorphism Fok1 with the risk or survival of pancreatic cancer in Egyptian population.

BACKGROUND AND AIMS: Pancreatic cancer (PC) is the fourth most common cause of death from cancer in Egypt. Few studies have been conducted to assess the relationship between vitamin D serum level and vitamin D receptor (VDR) polymorphisms with the survival of PC patients. This is the first study in Egypt to investigate the association of the status of vitamin D serum level and genotypic distribution of single nucleotide polymorphisms (SNP) Fok1 with the risk of developing PC and whether they could detect survival or not. PATIENTS AND METHODS: The study included a total of 47 PC cases that were histopathologically proven to have PC, and 37 controls that were attending at the same time for investigation but proved that they were all PC free. Pre-diagnostic concentrations of vitamin D and VDR polymorphism Fok1 were assessed from all participants in the study. RESULTS: There was a 1.5-fold increase in the serum level of vitamin D in PC patients when compared to non-PC subjects. Regarding VDR Fok1, polymorphism distribution in PC was CC (Wild Type) 26 (55.3%), CT 16 (34%), and TT 5 patients (10.7%). For the control group, CC was found in 24 (64.8%), CT in 12 (32.4%), and TT genotype was found only in one individual 1 (2.8%) with no statistically significant difference between the two studied groups (P 0.72). CONCLUSION: Low serum vitamin D or VDR-SNP is not a risk factor for PC in Egyptian patients. Recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer and improving overall survival should be carefully considered.

Serum MicroRNA-21 Negatively Relates to Expression of Programmed Cell Death-4 in Patients with Epithelial Ovarian Cancer

Background: Ovarian cancer is the third most common cancer of the female genital tract and the leading cause of cancer death associated with gynecologic tumors. MicroRNAs regulate at least 60% of human genes, including tumor suppressor genes and oncogenes and, thereby, can affect cancer risk. Aim of the work: We aimed to assess any diagnostic role for serum miR-21 as a biomarker in human ovarian cancer and to study relations with programmed cell death-4 (PDCD4), one of its target proteins, hoping to help explain heterogeneity of this cancer type and facilitate stratification of regimens for therapy. Subjects and Methods: A total of 60 newly diagnosed ovarian cancer cases and 30 apparently healthy females were recruited. Serum microRNA-21 levels were measured by TaqMan- Real time PCR assay and PDCD4 by ELISA. Results: Significant over-expression of serum miR-21 and lower serum PDCD4 levels were observed in ovarian cancer patients as compared to the control group. A statistically significant inverse correlation was also evident between miR-21 and PDCD4. However, no significant links were noted observed between miR-21 and tumor grade, stage or histopathological type. Conclusion: The present work showed significantly up-regulation of serum miR21 in the recruited group of patients and a significant inverse relation association between miR-21and PDCD4. These findings suggest that miR-21 may be used as a diagnostic biomarker for human ovarian cancer.

Clinical Impact of Overexpression of FOXP3 and WT1 on Disease Outcome in Egyptian Acute Myeloid Leukemia Patients

Background: In the last decade, it has become clear that change of gene expression may alter the hematopoietic cell quiescent state and consequently play a major role in leukemogenesis. WT1 is known to be a player in acute myeloid leukemia (AML) and FOXP3 has a crucial role in regulating the immune response. Objectives: To evaluate the impact of overexpression of WT1and FOXP3 genes on clinical course in adult and pediatric AML patients in Egypt. Patients and methods: Bone marrow and peripheral blood samples were obtained from 97 de novo non M3 AML patients (63 adult and 34 pediatric). Real-time quantitative PCR was used to detect overexpression WT1 and FOXP3 genes. Patient follow up ranged from 0.2 to 39.0 months with a median of 5 months. Results: In the pediatric group; WT1 was significantly expressed with a high total leukocyte count median 50X109/L (p=0.018). In the adult group, WT1 had an adverse impact on complete remission induction, disease-free survival and overall survival (p=0.02, p=0.035, p=0.019 respectively). FOXP3 overexpression was associated with FAB subtypes AML M0 +M1 vs. M2, M4+M5 (p =0.039) and the presence of hepatomegaly (p=0.005). Conclusions: WT1 and FOXP3 overexpression has an adverse impact on clinical presentation, treatment response and survival of pediatric and adult Egyptian AML patients.

Prognostic Value of Prepro-Gastrin Releasing Peptide in Lung Cancer Patients; NCI-Prospective Study

Background: Prior series investigated the expression of prepro-gastrin releasing peptide (prepro-GRP) in the peripheral blood of lung cancer patients. Our aim was to assess any prepro-GRP role as a prognostic factor for small cell lung cancer (SCLC) and NSCLC and correlations with clinical presentation and treatment outcome. Methods: A prospective study was conducted during the time period from the beginning of January 2012 till the end of January 2014. Prepro-GRP expression was analysed using a nested RT-PCR assay in peripheral blood of 62 untreated lung cancer patients attending the National Cancer Institute (NCI), Cairo University, and 30 age and sex matched healthy volunteers. Results: Among the 62 lung cancer cases, there were 24 (38.7%) SCLC, and 38 (61.3%) NSCLC (10 squamous cell carcinomas, 12 adenocarcinomas, 11 large cell carcinomas, 4 undifferentiated carcinomas, and 1 adenosquamous carcinoma). Twenty six patients (41.9%) were prepro-GRP positive. Prepro-GRP expression was higher (58.3%) among SCLC patients compared to NSCLC (squamous cell carcinoma (15.4%), large cell carcinoma (36.4%), and adenocarcinoma (25%)). Mean OS among prepro-GRP negative cases was longer than that among preprogastrin positive cases (17.6 vs 14.9 months). The mean PFS durations among preprogastrin negative versus positive cases were 7.7 vs 4.6 months (p= 0.041). No difference in response to chemotherapy was identified between the groups (p=0.983). Conclusion: Prepro-GRP is suggested to be a useful prognostic marker for lung cancer patients, especially with the fast- growing, bad prognostic SCLC type. More studies should aim at detailed understanding of the mechanisms of prepro-GRP action and its use in monitoring the response to treatment in a larger cohort.