ABSTRACT
Diagnosis of breast cancer by using sensitive and specific biomarkers is necessary. Cell- free DNA (cf-DNA) is a candidate biomarker in various cancers. Contrasting, shorted uniformed DNA released from apoptotic non-diseased cells, DNA released from malignant cells varies in size. DNA integrity is a ratio between 247 and 115 bp. This study aimed to evaluate the diagnostic values of cf-DNA using ALU -247 and ALU- 115 and DNA integrity in peripheral blood of breast cancer patients as a noninvasive marker. Also, to determine correlations between ALU-247 and ALU-115, DNA integrity, cancer antigen (CA )15-3 and carcinoembryonic antigen (CEA) with each other in breast cancer patients and in different stages of breast cancer. This study included 100 females, divided into 3 groups. The first group consisted of 20 apparently healthy females as the control group. The second group included 20 patients with benign breast lesions. The third group included 60 patients with breast cancer. Serum levels of both ALU-247 and ALU-115 as well as cf-DNA integrity were statistically significant higher in breast cancer patients as compared to the control group (p=0.018, p < 0.001 and p=0.009 respectively). Compared to the control group, ALU-247 had the best diagnostic sensitivity for diagnosis of breast cancer (86.78%) with 75% specificity with area under the curve of 0.848. We concluded that measuring ALU-247, ALU-115 and DNA integrity in peripheral blood would be a promising novel approach for diagnosis and early detection of breast cancer.
Subject(s)
Breast Neoplasms , Cell-Free Nucleic Acids , Female , Humans , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Cell-Free Nucleic Acids/geneticsABSTRACT
Little is known about abundance level changes of circulating microRNAs (miRNAs) and messenger RNAs (mRNA) in patients with Ebstein's anomaly (EA). Here, we performed an integrated analysis to identify the differentially abundant miRNAs and mRNA targets and to identify the potential therapeutic targets that might be involved in the mechanisms underlying EA. A large panel of human miRNA and mRNA microarrays were conducted to determine the genome-wide expression profiles in the blood of 16 EA patients and 16 age and gender-matched healthy control volunteers (HVs). Differential abundance level of single miRNA and mRNA was validated by Real-Time quantitative PCR (RT-qPCR). Enrichment analyses of altered miRNA and mRNA abundance levels were identified using bioinformatics tools. Altered miRNA and mRNA abundance levels were observed between EA patients and HVs. Among the deregulated miRNAs and mRNAs, 76 miRNAs (49 lower abundance and 27 higher abundance, fold-change of ≥2) and 29 mRNAs (25 higher abundance and 4 lower abundance, fold-change of ≥1.5) were identified in EA patients compared to HVs. Bioinformatics analysis identified 37 pairs of putative miRNA-mRNA interactions. The majority of the correlations were detected between the lower abundance level of miRNA and higher abundance level of mRNA, except for let-7b-5p, which showed a higher abundance level and their target gene, SCRN3, showed a lower abundance level. Pathway enrichment analysis of the deregulated mRNAs identified 35 significant pathways that are mostly involved in signal transduction and cellular interaction pathways. Our findings provide new insights into a potential molecular biomarker(s) for the EA that may guide the development of novel targeting therapies.
Subject(s)
Ebstein Anomaly/genetics , Gene Regulatory Networks , MicroRNAs/genetics , RNA, Messenger/genetics , Adolescent , Adult , Ebstein Anomaly/metabolism , Female , Humans , Male , MicroRNAs/metabolism , RNA, Messenger/metabolism , TranscriptomeABSTRACT
BACKGROUND: This study applied tissue Doppler imaging and color tissue Doppler imaging to study atrial function changes in patients with hypertrophic cardiomyopathy (HCM). The profile of the segmental atrial velocities and the strain rate were determined and compared with those of normal matched control subjects. METHODS: This study investigated 20 patients with HCM and 20 age-matched healthy control subjects. In a four-chamber apical view, tissue Doppler imaging was used to measure the lateral left and right atrial (LA and RA) and interatrial septal (IAS) wall systolic, early, and late diastolic velocities. Similarly, the atrial strain rate during ventricular systole (SR(S)) and the early (SR(E)) and late (SR(A)) diastolic phases in patients and control subjects were measured. The interventricular septal tissue Doppler-derived isovolumic relaxation time was calculated. RESULTS: Only the IAS annular and middle segments showed a significant reduction in the early diastolic velocity (mean, 4.01 +/- 2.2 vs 8.7 +/- 1.1, p = 0.001; 3.23 +/- 2 vs 6.01 +/- 1.9, p = 0.001, respectively) for the patients with HCM in comparison with the control subjects. Generally, the atrial strain rate was clearly reduced. The systolic strain rate (SR(S)) was significantly reduced in the LA wall in the annular (p = 0.007) and middle (p = 0.001) segments and in the IAS middle segment (p = 0.007). Similarly, there was a reduction of the early diastolic strain rate (SR(E)) in the LA annular (p = 0.001) and middle (p = 0.01) segments and in the IAS annular (p = 0.05) and middle (p = 0.001) segments, as well as in the RA annular segment (p = 0.02). The RA middle segments showed insignificant changes. CONCLUSION: Atrial function may be affected by HCM due to impairment of myocardial diastolic function. Strain rate imaging is reproducible, yields readily obtained parameters that provide unique data about global and longitudinal segmental atrial contraction, and can quantify the atrial dysfunction in patients with HCM.
