RESUMO
Cancer cells have an altered transcriptome, which contributes to their abnormal behavior. Many tumors have high levels of kinetochore genes, which play important roles in genome stability. This overexpression could be utilized to destabilize cancer cell genomes, however this has not been proven specifically. We investigated the link between kinetochore gene overexpression, chromosomal number variations (CNVs) and genomic instability. Data on RNA expression and CNV from 12 different cancer types were evaluated using information theory. In all cancer types, we looked at the relationship between RNA expression and CNVs. Kinetochore gene expression was found to be substantially linked with CNV levels. In all cancer types, with the exception of thyroid cancer, highly expressed kinetochore genes were enriched in the most dominant cancer-specific co-expression subnetworks characterizing the largest patient subgroups. Except for thyroid cancer, kinetochore inner protein CENPA was among the transcripts most strongly associated with CNV values in all cancer types studied, with significantly higher expression levels in patients with high CNVs than in patients with low CNVs. CENPA function was investigated further in cell models by transfecting genomically stable (HCT116) and unstable (MCF7 and HT29) cancer cell lines using CENPA overexpression vectors. This overexpression increased the number of abnormal cell divisions in the stable cancer cell line HCT116 and, to a lesser extent, in the unstable cell lines MCF7 and HT29. Overexpression improved anchorage-independent growth properties of all cell lines. Our findings suggest that overexpression of kinetochore genes in general, and CENPA in particular, can cause genomic instability and cancer progression.
RESUMO
Management of ß-thalassemia in developing countries is demanding in the absence of available therapies rather than recurrent transfusions. This study describes the characteristics and evaluates the hematological, biochemical, and hormonal findings of patients with ß-thalassemia in the West Bank. We conducted a retrospective cohort study between January 2017 and December 2018. Data were collected through medical files of the patients with ß-thalassemia from eight primary healthcare clinics, nine emergency departments, and 11 governmental hospitals across the West Bank. Results of the hematological, biochemical, and hormonal evaluations, in addition to demographic data and the use of iron chelation were included in the study and analyzed. A total of 309 patients with ß-thalassemia were included with a male-to-female ratio of 1:1 and an average age of 23.4 ± 10.4 years. The anemic presentation was reported in 78.6% of the patients as indicated by hemoglobin level (mean ± SD = 8.4 ± 1.4 g/dl), and 73.1% had iron overload with serum ferritin (SF) levels ≥ 1,000 µg/L (mean ± SD = 317.8 ± 3,378.8 µg/L). Evaluation of the liver function tests showed that alanine transaminase (ALT) and aspartate transaminase (AST) levels were high among 38.1 and 61.2% of the patients, respectively. ALT and AST showed significant positive correlations with SF levels, while the kidney tests did not. As for iron chelation medications, patients receiving deferoxamine (26.5%) showed significantly higher SF levels compared with patients receiving deferasirox (73.5%). This study highlights the importance of establishing patient-tailored comprehensive assessment and follow-up protocols for the management of ß-thalassemia with an emphasis on blood transfusion and iron chelation practices.
