Background
Abnormal expression patterns of microRNAs (miRs) play an important role in the development and progression of malignancy. Identification of the clinical significance and prognostic value of these small molecules in chronic lymphocytic leukemia (CLL); a disease of heterogeneous biological landscape and clinical course, has always been of tremendous translational value.
Aim
To evaluate the prognostic value of microRNA17-92 cluster members in Egyptian CLL patients.
Methods
The expression levels of miR17-92 cluster members were evaluated by qRT-PCR, including miR17, miR18a, miR19a, miR19b-1, miR20a, and miR92a-1. Other investigations included serum LDH, serum β2 microglobulin (β2M), CD38 and ZAP70 expression by flow cytometry, fluorescence in situ hybridization (FISH) for 17p deletion, and imaging studies (computerized tomography (CT) scans of neck, chest, abdomen, and pelvis or PET-CT scans).
Results
Overexpression of all members of the miRNA17-92 cluster was detected in CLL patients compared to controls (p = < 0.001 for all miRs while p = 0.01 for miR19b-1). A significant positive correlation between Hb and miR17 and a significant negative correlation between Hb and miR19b-1 were observed (p = 0.041, 0.017 respectively). A statistically significant positive correlation between miR19b-1 expression and each of the WBCs and absolute lymphocytic count (ALC) was detected (p = 0.023, 0.022 respectively). Moreover, a statistically significant relation between miR19b-1 expression and advanced Binet stages was also found (p = 0.05). Regarding miR18a, a statistically significant positive correlation with LDH level was found (p = 0.003). We also found a significant positive correlation between miR92a-1 and β2M level (p = 0.005), as well as a significant relation between miR17 and negative CD38 expression (p = 0.034). However, no significant relationships between any of studied miRNA expression levels and 17p deletion or response to treatment were observed. Patients who expressed miR19b-1 were significantly indicated to start therapy at diagnosis (p = 0.05). The overall survival of CLL patients included in our study was 90.2% after 1 year from the time of diagnosis. Patients with high expression of miR19a had better OS than those with low expression (p = 0.04).
Conclusions
Overexpression of all members of the miR17-92 cluster was detected in Egyptian CLL patients. MiR18a, miR19b-1, and miR92a-1 also have an adverse prognostic value while miR17 can be considered a good prognostic marker. High expression of miR19a is associated with better OS.
The molecular biomarkers, and their correlation with pathological parameters are very important for diagnosis, prognosis, predictive utility, management, and prevention of breast cancer (Patani et al., 2013). The phosphatidylinositol-3-kinase (PI3K) pathway is an important signaling pathway in cells and is involved in essential cellular functions such as metabolism, proliferation, survival, motility, and growth and plays a main role in development and progression of breast cancer (Engelman et al., 2006; Boyault et al., 2012). Based on structure, regulation, and substrate specificity, the PI3K family is classified into three classes, class I, class II, and class III (Leevers et al., 1999). Class I is divided to IA and IB, class IA PI3K is composed of two subunits: A regulatory subunit (85 kDa), and a catalytic
Breast cancer (Bc) is the most commonly diagnosed cancer worldwide and a major health concern in egypt. There is a known association between pathogenic variants identified in breast cancer susceptibility gene (BRCA)1 and 2 and the risk of developing Bc. However, the number of studies investigating mutations in BRCA1 and BRCA2 in egypt remains limited. Thus, the aim of the present study was to investigate the frequency of BRCA1 and BRCA2 variants in patients with Bc and their relatives. For this purpose, 11 families (11 patients and 16 relatives) were included in the present study. BRCA1 and BRCA2 variants were investigated using the ion S5 next-generation sequencer. it was found that pathogenic variants were more frequent in patients with familial Bc (FBc) than in those with sporadic Bc, with 71% of variants in BRCA2, including the first reported identification of c.9089del, c.5583_5584dup, c.8243G>A and c.7976G>A pathogenic variants in Egyptian patients with BC. Pathogenic variants in relatives were confined to FBC c.1278delA, c.1960_1961del, and c.1224delT, with a higher incidence of variants of uncertain significance (VUS), such as BRCA2 intron 2 c.68-16delT. of note, two cold spot benign variants, c.3113A>G and c.4837A>G, were repeatedly found (67%) in patients and relatives. in conclusion, to the best of our knowledge, novel pathogenic variants and VUS in Egyptian patients with BC and their high-risk relatives were identified for the first time in the present study. These findings should be integrated with other genomic data concerning egyptian families and carefully interpreted during genetic counseling.
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