Clinical significances and diagnostic utilities of both miR-215 and squamous cell carcinoma antigen-IgM versus alpha-fetoprotein in Egyptian patients with hepatitis C virus-induced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It has been widely established that the early detection of HCC enables more treatment options with improvements in prognosis and survival. OBJECTIVES: The aim of this study was to assess the diagnostic accuracy of both circulating miR-215 and squamous cell carcinoma antigen-IgM (SCCA-IgM) as serum biomarkers for HCC by examining their diagnostic sensitivity, specificity, accuracy, and predictive values in hepatitis C virus (HCV)-induced HCC patients. SUBJECTS AND METHODS: This study included 60 patients with HCV-related HCC. In addition, 60 patients with HCV-related liver cirrhosis (LC) and 60 apparently healthy subjects were involved, and served as diseased and healthy control groups, respectively. The relative expression levels of miR-215 were detected using quantitative real-time PCR. SCCA-IgM levels in serum were measured by enzyme immunoassay. We used receiver operating characteristic (ROC) curve to calculate the diagnostic accuracy against alpha-fetoprotein (AFP). RESULTS: Relative miR-215 expression levels increased the most in HCC patients compared to that in healthy or diseased controls (P<0.001). Serum concentration of SCCA-IgM was significantly higher in HCC group than that in the two control groups. We performed multivariate analysis using AFP level, focal lesion size, and portal vein thrombosis as independent variables. ROC curves showed that the optimum diagnostic miR-215 cutoff value for identifying HCC patients from cirrhotic ones was 417 (sensitivity, 97%; specificity, 91%) and for SCCA-IgM was 95 AU/mL (sensitivity, 92%; specificity, 98%). Moreover, the superiority of both miR-215 and SCCA-IgM to AFP is obvious in our study and this superiority is more evident in distinguishing HCC with AFP levels <200 ng/mL and HCC patients with small-sized focal lesions from cirrhotic patients. CONCLUSION: Cell-free miR-215 and serum SCCA-IgM could be used for early diagnosis of HCC either each one as a single marker or with AFP complement measurement.

Expression of chemerin correlates with a poor prognosis in female breast cancer patients.

OBJECTIVE: Chemerin was reported to regulate adipogenesis, metabolism, and immunity. But, its relation to cancer remains controversial. In breast cancer, chemerin expression has only been studied in serum, however, its expression in tissue, to our knowledge, has not been studied. The aim of this study was to investigate chemerin expression in breast cancer tissue in comparison to the adjacent normal tissue, and to assess its relationship to disease prognosis. METHODS: We examined chemerin expression in tissue with immunohistochemistry and analyzed the association of chemerin expression with the patients' clinical and pathological characteristics to determine its role as a predictor of the disease and its relation to disease prognosis. RESULTS: We detected a significantly higher expression of chemerin in the malignant vs the non-cancerous tissue specimens in 30/53, (56%) patients, (P=0.001). Moreover, its expression was significantly higher in the metastatic lymph nodes in comparison to the tumor tissues, (P=0.01). Chemerin expression was significantly correlated with weight (r=0.256, P=0.04), body mass index (r=0.233, P=0.03), tumor size (r=0.235, P=0.03), lymph node metastasis (r=0.265, P=0.045), distant metastasis (r=0.267, P=0.02), and tumor grading, (r=0.421, P=0.004), while it was inversely significantly correlated with estrogen receptor and progesterone receptor expression in malignant breast tissues (P=0.038, r=-0.437, and P=0.047, r=-0.316), respectively. The area under the receiver operating characteristic curve for chemerin as a predictor of breast cancer was 0.82, (P<0.001, sensitivity 89%, and specificity 69%). The Kaplan-Meier survival curves revealed that patients with higher chemerin expression had worse overall survival in comparison to those with a lower chemerin expression, (P=0.001). CONCLUSION: Our results revealed higher chemerin expression in malignant vs adjacent normal breast tissue and lend support to a presumable role of chemerin tissue expression as an independent predictor of poor prognosis in breast cancer patients.

A study of the circulating fibroblast growth factor 21 as a novel noninvasive biomarker of hepatic injury in genotype-4 chronic hepatitis C: Egyptian patients and their response to direct-acting antiviral agents.

BACKGROUND: Fibroblast growth factor (FGF) 21 was reported to be induced by different injurious agents, including chronic hepatitis C (CHC) virus, affecting the liver. The aims of this study were to evaluate the FGF21 levels in CHC patients before and after the treatment with direct-acting antiviral agents (DAAs) in comparison to that in control subjects and to correlate these levels with insulin resistance (IR), lipid profile, and fibrosis stages. PATIENTS AND METHODS: We studied 75 naive CHC patients and 40 age- and gender-matched healthy control subjects. Patients were divided into five groups based on the severity of fibrosis as detected by Fibroscan as follows: F0, n=2; F1, n=13; F2, n=23; F3, n=16; F4, n=21. We estimated the FGF21 levels at the start of the study for all the participants and for the patients only at the end of treatment with simisipivir (SIM) and sofosbuvir (SOF). These levels were compared between the patients and the control subjects and also for the patients before and after the treatment with DAAs. The FGF21 levels were correlated to IR, lipid profile, and stages of liver fibrosis. RESULTS: The FGF21, fasting blood sugar (FBS), fasting insulin, and homeostasis model of IR (HOMA-IR) were significantly higher in CHC patients compared to control (5.04±0.75 vs 4.7±0.52, 20.15±5.13 vs 13.15±4.2, 4.49±1.28 vs 2.72±0.87, and 123.7±52.6 vs 21.8±8.8; P≤0.01, P≤0.001, P≤0.001, and P≤0.001, respectively). The posttreatment FGF21 levels were significantly reduced when compared to the pretreatment levels (123.7±52.5 vs 60.5±32.7, P≤0.001). FGF21 levels showed significant negative correlation with FBS and positive correlation with serum albumin (P≤0.05 and P≤0.003, respectively). The multiple linear regression analysis revealed that serum albumin, high-density lipoprotein cholesterol (HDL-c), and the stage of liver fibrosis were independent risk factors for FGF21. CONCLUSION: Besides its metabolic modulator role, FGF21 strongly introduced itself as a novel biomarker of hepatic injury in Egyptian, genotype-4, CHC patients.

The Role of Signal Transducer and Activator of Transcription 5 and Transforming Growth Factor-ß1 in Hepatic Fibrosis Induced by Chronic Hepatitis C Virus Infection in Egyptian Patients.

OBJECTIVE: To investigate the possible role of signal transducer and activator of transcription 5 (STAT5) in the pathogenesis of liver fibrosis in Egyptian patients with chronic hepatitis C (CHC) virus infection and its relation to hepatic stellate cells (HSC). SUBJECTS AND METHODS: Sixty-five patients (46 males and 19 females) were divided into 4 groups based on the severity of fibrosis as detected by Fibroscan as follows: F1, n = 15; F2, n = 21; F3, n = 13; and F4, n = 16. Twenty age- and gender-matched healthy persons volunteered as controls. The serum levels of STAT5, TGF-ß1, α-smooth muscle actin (α-SMA), fasting blood sugar, and fasting insulin, as well as homeostasis model assessment of insulin resistance (HOMA-IR), were determined and compared for all groups. The usefulness of the studied serum biomarkers for predicting liver fibrosis was evaluated using a receiver operating characteristic curve. RESULTS: Serum levels of STAT5 were significantly lower in patients compared to controls (9.69 ± 5.62 vs. 14.73 ± 6.52, p ≤ 0.001); on the contrary, TGF-ß1, α-SMA, and HOMA-IR were significantly higher in patients compared to controls (mean: 1,796.04 vs. 1,636.94; 14.94 vs. 8.1; and 7.91 vs. 4.18; p ≤ 0.01 and 0.001, respectively). TGF-ß1 and α-SMA showed a progressive increase with advancing severity of hepatic fibrosis (mean TGF-ß1: 2,058.4 in F1-F2 and 1,583.8 in F3-F4, p ≤ 0.04; mean α-SMA: 13.59 in F1-F2 and 16.62 in F3-F4, p ≤ 0.05). STAT5 had a significant negative correlation with TGF-ß1 (p ≤ 0.001), while no correlation was detected with α-SMA (p ≤ 0.8). CONCLUSIONS: STAT5 may play a significant role in hepatic fibrogenesis through the induction of TGF-ß1 but not through the activation of hepatic stellate cells.

Study of changes in lipid profile and insulin resistance in Egyptian patients with chronic hepatitis C genotype 4 in the era of DAAs.

Chronic hepatitis C virus (HCV) infection is associated with altered metabolism, including dyslipidemia and insulin resistance. These contribute to disease progression and influences the response to therapy. To investigate the relationships of new direct-acting antiviral drugs, simeprevir/sofosbuvir, with lipid profile and insulin resistance (IR). Eighty chronic hepatitis C genotype 4 patients were included; they were divided into four groups according to the severity of fibrosis as detected by fibroscan. Forty healthy persons volunteered as a control group. Lipid profile changes and IR were analyzed at baseline and after the end of treatment, and any effect of these changes on the response to treatment was studied. Before treatment, the levels of serum triglycerides were significantly higher in patients than in the control, and the levels of fasting insulin showed a progressive increase with advancing stage of fibrosis. At the end of treatment, there were a significant reduction in serum triglycerides, FBS, fasting insulin, and homeostasis model for the assessment of IR (P < 0.001), and a significant elevation of serum cholesterol and low-density lipoprotein (LDL)-c, high-density lipoprotein (HDL)-c, and LDL/HDL ratio (P = 0.001). An end-of-treatment response (week 12) was achieved in (99%) of the treated cases with 99% sustained viral response for 12 weeks post-treatment (week 24). Significant lipid profile changes were detected at the end of treatment. Serum lipid levels and IR are no longer predictors of response to DAAs. Follow-up of the lipid profile is warranted to avoid any possible remote effect of atherosclerotic heart disease.