Plasma CD24 level as a promising prognostic biomarker of hepatocellular carcinoma

Abstract Background Hepatocellular carcinoma constitutes the most common primary hepatic cancer and remains a major medical burden in both developing and developed world. It ranks fifth in terms of global cases and second in terms of deaths for males.CD24 is known as a heavily glycosylated cell surface molecule that is highly expressed in a wide variety of human malignancies. It plays an important role in self-renewal, proliferation, migration, invasion, and drug resistance. The aim of this work was to evaluate the potential role of serum CD24 in the diagnosis and prediction of response to interventional therapy among hepatocellular carcinomas. Methods This study included 40 adult Egyptian patients who had liver cirrhosis and hepatocellular carcinoma (HCC group). Another group of 20 patients with liver cirrhosis only served as controls (Cirrhosis group). All patients underwent standard laboratory tests and abdominal ultrasound. For HCC patients, a triphasic CT scan, alpha-fetoprotein was done. CD24 levels were measured in all patients, and in HCC patients at baseline and one month after intervention. Results Baseline CD24 was significantly higher among HCC group in comparison to cirrhosis group (19.463 ± 8.573 vs. 0.725 ± 0.125 mg/L) with an overall p value < 0.001. Serum CD24 levels significantly declined after locoregional treatment from 19.463 ± 8.573 mg/L to 3.569 ± 1.248 mg/L (p < 0.001). Baseline CD24 was a useful marker in eligibility for HCC intervention with 80% sensitivity and 74.29% specificity at a cutoff of ≤ 23 mg/L, and it also had 62.96% sensitivity and 100% specificity in prediction of cure after locoregional treatment at a cutoff of ≤ 19.5 mg/L. Conclusion CD24 could be a helpful diagnostic and prognostic marker for HCC, as its baseline level is useful in predicting both eligibility for intervention and cure after locoregional treatment

HOTAIR expression and prognostic impact in acute myeloid leukemia patients

Abstract Background Acute myeloid leukemia (AML) is a disorder characterized by a rapid onset of symptoms attributable to bone marrow failure due to clonal proliferation of primitive hematopoietic stem cells or progenitor cells. Epigenetic abnormalities play an important role in the development and progression of acute leukemia. Long non-coding ribonucleic acid (lncRNA) plays an important role in epigenetic regulation. Homeobox (Hox) transcript antisense intergenic RNA (HOTAIR) is a lncRNA which has been determined to be a negative prognostic indicator in various solid-tumor patients. However, its role in hematopoietic tumors as AML is to be assessed. This study aimed at measuring lncRNA HOTAIR expression level on bone marrow (BM) mononuclear cells in newly diagnosed AML patients and correlating its expression with their outcome and different prognostic variables. This provides new prospective for a novel marker involved in development and progression of AML which can be used as a diagnostic marker and a target of therapy. The current study included 65 subjects divided into 35 newly diagnosed AML adult patients (before initiation of chemotherapy) and 30 non-leukemic adult patients who are candidates for BM aspiration for causes other than hematological malignancies as immune thrombocytopenic purpura and hypersplenism as controls. HOTAIR expression was measured on BM mononuclear cells by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results HOTAIR expression was found to be significantly upregulated in AML patients (probability (p) value = 0.000) and it can be used as a diagnostic biomarker of AML as confirmed by a significant difference between cases and controls using receiver operating characteristic curve (ROC) analysis. However, it was not significantly correlated with event free survival (EFS) or prognostic variables. Conclusion This study showed that the expression of HOTAIR is upregulated in de novo AML patients and can be used as a diagnostic marker. However, highly expressed HOTAIR is not associated with poor prognosis

Microelimination of hepatitis C in patients with chronic hemolytic anemias: a single-center experience

Abstract Background Patients with chronic hemolytic anemias (CHA) are at a high risk for transfusion-transmitted infections. Various studies in Egypt have shown a prevalence of hepatitis C virus (HCV) infection in 24–37% of those patients. Elimination of hepatitis C virus (HCV) in patients with CHA would prevent early progression of liver disease. In this study, we aimed to assess the efficacy, safety, and tolerability of sofosbuvir (SOF) and daclatasvir (DAC) in the special population of HCV-infected patients with CHA. In this prospective study, 21 consenting hepatitis C patients were recruited and treated using ribavirin-free SOF/DAC regimen for either 12 or 24 weeks according to categorization of patients into easy or hard-to-treat in accordance with the national protocols. Sustained virological response was assessed by RT-PCR for HCV-RNA at 12 weeks post-treatment (SVR12). Any treatment-related adverse events were noted. Results All patients were adherent to treatment with no discontinuation of therapy. SVR12 was achieved in 19 out of 21 patients (90.5%). There was a significant improvement in levels of ALT (p<0.009) after completion of therapy. On the other hand, the hemoglobin, total bilirubin, and ferritin levels showed a non-significant difference (p<0.501, p<0.542, and p<0.339, respectively). Moderate adverse events were observed in 2 out of 21 patients (9.5%), including sickling crisis and hepatic decompensation. Conclusion The results of this study substantiate the favorable efficacy, safety, and tolerability of ribavirin-free direct-acting antivirals (DAAs) in the special population of HCV-infected patients with CHA. Micro-elimination of HCV in special patient populations allows for pragmatic delivery of care to patients with co-morbid conditions who are in most need for treatment and allows for achievement of global elimination of HCV worldwide

Down-regulation of MSH3 and MSH6 genes in female breast cancer patients receiving taxane-based therapy

Abstract Background The DNA in each cell in our body is constantly in danger of becoming damaged. Most DNA damage gets repaired straight away via many different proteins encoded by DNA—repair genes. MSH3 and MSH6 are pivotal DNA repair genes maintaining human genome integrity. Dysregulated expression of such genes has its implications resulting in developing of adverse reactions in cancer breast patients receiving taxanes. Cancer chemotherapy with some of taxane class of agents are associated with significant neurotoxicity, arthralgias and myalgias that may offset the therapeutic benefits of taxane use. Our aim is to identify gene expression pattern of MSH3 and MSH6 DNA mismatch repair genes in female breast cancer patients who develop adverse reactions to taxane-based therapy. One hundred and five patients with histologically proven breast cancer who received paclitaxel (PTX) as a single agent or combination therapy have been enrolled along with a group of 50 females with benign breast lesions serving as controls.Gene expression studies of mismatch repair genes (MMR) genes; MSH3 and MSH6; have been performed by real-time PCR. Patients were divided into groups according to the determined type/grade of PTX-based toxicity and fold changes of both genes were estimated. Results In the present work both MMR genes showed significantly lower expression in all the studied patients compared to benign cases as a control group. Toxicity findings were encountered in 75.2% of the studied patient cohort. The most common observed type of toxicity was peripheral neuropathy (PN), 58.1% of the studied patients. Both MSH3 and MSH6 genes were significantly down-regulated in the presence of high grade PN toxicity ≥ 2 (p = 0.034 and 0.01); diarrhea toxicity (p = 0.02 and 0.008); dyspnea (p = 0.01 and 0.016) respectively and bone pain (p = 0.024 for MSH6 only). Conclusion Dysregulated expression of MMR GENES [MSH3and MSH6] can be implicated in paclitaxel—induced toxicity experienced by some cancer breast patients

CYP2C8 rs11572080 and CYP3A4 rs2740574 risk genotypes in paclitaxel-treated premenopausal breast cancer patients

Abstract Breast cancer (BC) is the most prevalent malignancy in women globally. At time of diagnosis, premenopausal BC is considered more aggressive and harder to treat than postmenopausal cases. Cytochrome P450 (CYP) enzymes are responsible for phase I of estrogen metabolism and thus, they are prominently involved in the pathogenesis of BC. Moreover, CYP subfamily 2C and 3A play a pivotal role in the metabolism of taxane anticancer agents. To understand genetic risk factors that may have a role in pre-menopausal BC we studied the genotypic variants of CYP2C8, rs11572080 and CYP3A4, rs2740574 in female BC patients on taxane-based therapy and their association with menopausal status. Our study comprised 105 female patients with histologically proven BC on paclitaxel-therapy. They were stratified into pre-menopausal (n = 52, 49.5%) and post-menopausal (n = 53, 50.5%) groups. Genotyping was done using TaqMan assays and employed on Quantstudio 12 K flex real-time platform. Significant increased frequencies of rs11572080 heterozygous CT genotype and variant T allele were established in pre-menopausal group compared to post-menopausal group (p = 0.023, 0.01, respectively). Moreover, logistic regression analysis revealed a significant association between rs11572080 CT genotype and premenopausal BC. However, regarding rs2740574, no significant differences in genotypes and allele frequencies between both groups were detected. We reported a significant association between CYP2C8 genotypic variants and premenopausal BC risk in Egyptian females. Further studies on larger sample sizes are still needed to evaluate its importance in early prediction of BC in young women and its effect on treatment outcome