RESUMO
Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide, and especially in Egypt. Early diagnosis of HCC greatly improves the survival and prognosis of patients. Low sensitivity and specificity of alpha-fetoprotein (AFP) has led to the demand for novel biomarkers of HCC. The aim of the present study was to evaluate the validity of frizzled-7 (FZD7) and glypican-3 (GPC3) gene expression as potential biomarkers for HCC early diagnosis, and to investigate the association between FZD7 rs2280509 polymorphism and HCC risk. Materials and methods: Quantification of FZD7 and GPC3 gene expression by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay, and genotyping FZD 7 (rs2280509 SNP) gene polymorphism using RT-PCR. Results: The current results revealed that FZD7 gene expression had a greater area under the curve (AUC) for identifying HCC than GPC3 gene expression and AFP levels. The combination of the three markers as a panel showed a better diagnostic performance with a greater AUC than any of the single markers alone (p < 0.05). The FZD7 rs2280509 polymorphism (CT) was found to be significantly associated with an increased risk of HCC. The CT genotype and T allele were significantly more prevalent in the HCC group compared to either the cirrhosis (p = 0.03) or control groups (p = 0.0009 and 0.002; respectively). Conclusion: FZD7 and GPC3 gene expressions have a complementary role in early HCC detection, with a greater diagnostic sensitivity and accuracy than AFP. In addition, FZD7 rs2280509 polymorphism is significantly associated with an increased risk of HCC in the Egyptian population.
RESUMO
BACKGROUND: Red blood cell (RBC) aging in transfusion medicine is characterized by alteration of many biochemical and morphological integrity of the cell referred to as red cell storage lesion (RCSL), CD47 is a protective marker expressed on RBCs that salvage the cell from phagocytosis. 2,3-diphosphoglycerate (2,3-DPG) tends to have a greater affinity towards deoxygenated hemoglobin. Any oxygen unloading at tissue capillaries are facilitated by 2,3-DPG, and any alterations in its levels can significantly interfere with oxygen release. Alteration of both CD47 expression and 2,3-DPG levels during red cell storage may serve as markers in the development of RCSL. The aim of this study was to validate the impact of storage time and leuco-depletion on CD47 expression on the RBCs, which could be a prospective marker for detection of RBCs viability and to clarify if the changes in CD47 expression and 2,3-DPG levels are correlated during storage of Packed RBCs. SUBJECTS AND METHODS: One hundred samples from Packed RBCs units were divided into two groups [Group 1 comprised unfiltered packed red cell units (n=50), whereas Group 2 included filtered "leuco-reduced" red cell units (n=50)]. Collection of samples was executed on days 0, 1 and 21. Each sample was measured for 2,3-DPG and alteration of CD47 expression on RBC using flow cytometry. RESULTS: Decreased CD47 expression along the storage period was statistically significant in both groups (P<0.05). Interestingly, the expression of CD47 was significantly higher in group 2 than group 1 on day zero, 1st and 21st days (P<0.05). Additionally, a statistically significant decrease in 2,3-DPG level was detected at day 21 of storage in group 1 compared to group 2 with a P-value of <0.001. There was a significant positive correlation (r=0.570, P<0.001) between CD47 MFI on RBC during storage and the level of 2,3-DPG at day 21 from packed RBCs storage. CONCLUSION: Older unfiltered RBC possesses lower expression of CD47 and low levels of 2,3-DPG, however filtration (leucoreduction) of RBCs units may help to retain considerable levels of 2,3-DPG and CD47 and hence sustains preservation of RBCs through reduction of phagocytosis.
