Cartilage oligomeric matrix protein as a non-invasive biomarker for diagnosis of hepatocellular carcinoma in patients with liver cirrhosis.

Aim: The current study purposed to evaluate serum COMP (Cartilage oligomeric matrix protein) as a diagnostic marker for HCC in patients with cirrhosis and to correlate it with other parameters of disease progression. Background: COMP is known to promote fibrosis in various tissues. Emerging evidence shows that COMP plays critical roles in tumor development. It can serve as a fibrosis and cancer biomarkers. Methods: The study included 24 subjects who serve as the healthy control, 24 cirrhotic patients without HCC, and 24 HCC patients with cirrhosis. All participants were subjected to liver function tests, AFP, calculation of fibrotic indices (APRI and FIB-4), and serum COMP by ELISA. Results: COMP was significantly increased in cirrhotic patients when compared to healthy controls and in HCC patients when compared to cirrhotic patients and healthy controls. A significant positive correlation was observed between COMP and APRI and FIB-4 in cirrhotic and HCC patients. Based on receiver operating characteristic (ROC) curve analysis, COMP had an area under curve (AUC) of 0.943 with 87.5% sensitivity and 79.2% specificity for diagnosis of HCC in cirrhotic patients. In combination with AFP, the sensitivity was increased to 100%. Conclusion: COMP might act as a promising non-invasive biomarker for HCC either alone or in combination with AFP. It was correlated with the degree of fibrosis and associated with advanced cancer staging.

Analysis of FHIT gene methylation in egyptian breast cancer women: association with clinicopathological features.

BACKGROUND: Fragile histidine triad (FHIT) gene is a tumor suppressor gene which involved in breast cancer pathogenesis. Epigenetics alterations in FHIT contributes to tumorigenesis of breast cancer. OBJECTIVE: Our objective was to study FHIT promoter region hypermethylation in Egyptian breast cancer patients and its association with clinicopathological features. MATERIALS AND METHODS: Methylation-specific polymerase chain reaction was performed to study the hypermethylation of FHIT promoter region in 20 benign breast tissues and 30 breast cancer tissues. RESULTS: The frequency of hypermethylation of FHIT promoter region was significantly increased in breast cancer patients compared to bengin breast disease patients. The Odd ?s ratio (95%CI) of development of breast cancer in individuals with FHIT promoter hypermethylation (MM) was 11.0 (1.22-250.8). There were also significant associations between FHIT promoter hypermethylation and estrogen, progesterone receptors negativity, tumor stage and nodal involvment in breast cancer pateints. CONCLUSIONS: Our results support an association between FHIT promotor hypermethylation and development of breast cancer in Egyptian breast cancer patients. FHIT promoter hypermethylation is associated with some poor prognostic features of breast cancer.

Peroxisome proliferator activated receptor γ2 gene Pro12Ala gene polymorphism in type 2 diabetes and its relationship with diabetic nephropathy.

BACKGROUND: Despite intensive research, a genetic background of type 2 diabetes is still unknown as are causes of differences in the clinical course of the disease. This supports the hypothesis for factors of genetic susceptibility (or protection) to diabetic nephropathy. This study aimed to examine the association between Pro12Ala polymorphism in the PPARgamma2 gene with both type 2 diabetes and the development of diabetic nephropathy. METHODS: The study included seventy subjects classified into three groups: healthy control group (20), diabetics without nephropathy (25), and diabetics with nephropathy (25). All members of the study were subjected to the following laboratory investigations: fasting glucose and insulin with calculation of insulin resistance by HOMA IR, HbA1c, urea, creatinine and calculation of creatinine clearance, lipid profile, urinary protein and/or microalbumin. Determination of Pro12Ala polymorphism in PPARgamma2 gene was done by PCR/RFLP. RESULTS: As regards PPARgamma2 Pro12Ala gene polymorphism, the Pro/Pro genotype was the most common in diabetic patients as well as in controls followed by Pro/Ala genotype and Ala/Ala genotypes was the least common one. The genotype distribution of the PPARgamma2 polymorphism was significantly different in diabetic patients compared to controls and in diabetics with nephropathy compared to those without nephropathy (p < 0.05). The allelic frequency of proline (Pro) was significantly higher in diabetic patients than controls (p < 0.001) and also significantly higher in diabetics with nephropathy than without nephropathy (p < 0.05). The odds ratio (OR) of having diabetes for Pro allele carriers was 8 compared with noncarriers (95% CI: 2.66 - 23.98). CONCLUSIONS: Our results support the association between the Pro allele of PPARgamma2 gene and both development of type 2 diabetes and diabetic nephropathy.

Clinical relevance of serum endoglin level in Egyptian hepatocellular carcinoma patients.

BACKGROUND: In hepatocellular carcinoma (HCC), preferential expression of endoglin on endothelial cells of the tumor vasculature versus neoplastic cells has led to the suggestion that it originates from the neovasculature and plays an important role in angiogenesis. Our study aimed to evaluate the role of serum endoglin in the diagnosis of HCC and to correlate it with other studied prognostic markers. METHODS: Sixty hepatocellular carcinoma patients were studied, 60 cirrhotic patients and 45 matched healthy controls. Liver function tests, alpha fetoprotein (alphaFP) and serum endoglin levels were determined. RESULTS: The study revealed a significant increase in alphaFP and endoglin in patients with liver disease compared to controls and in HCC patients compared to cirrhotic ones. There was a positive correlation between both biomarkers and stages of HCC, whereas no significant correlation between endoglin and alphaFP or between both of them and Child Pugh's classification was seen. At a cutoff value of 20 ng/mL, the sensitivity of alphaFP was 75% and the specificity was 90%, in differentiating HCC from cirrhosis. At a 7.5 ng/mL cutoff, the sensitivity of endoglin was 70% and specificity was 65%. On combination of both biomarkers, the sensitivity was increased to 85%. CONCLUSIONS: Serum endoglin is a useful complementary biomarker in the diagnosis of HCC.

HE4 and mesothelin: novel biomarkers of ovarian carcinoma in patients with pelvic masses.

OBJECTIVES: To evaluate the utility of novel serum tumor markers, HE4 and mesothelin either alone or in combination with CA125 in diagnosis and early detection of ovarian carcinoma in patients with pelvic masses. SUBJECTS AND METHODS: Sera were obtained preoperatively from 65 women underwent surgery for a pelvic mass and 25 age- and menopausal status-matched healthy women. All samples were analyzed for levels of CA125, HE4, and mesothelin by serum based immunoassays and patients results were compared to final pathology findings. RESULTS: Of 65 patients with pelvic masses; 41 had histologically diagnosed ovarian cancer, and 24 had benign ovarian diseases. The studied tumor markers were significantly increased in malignant compared to benign cases and healthy subjects, and in benign cases compared to healthy subjects (p<0.001). Based upon Receiver operator characteristic (ROC) curves analysis, HE4 had the highest sensitivity as a single marker in detecting ovarian malignancy (82.9%) and early stage malignancy (76.9%), followed by CA125, then mesothelin. The combination of HE4 and CA125 gave the highest sensitivity in detecting ovarian carcinoma and early stage disease (90.2%, 84.6% respectively). Addition of mesothelin to this combination did not show any improvement in the sensitivity. CONCLUSIONS: As a single marker, HE4 had the highest sensitivity for detecting ovarian carcinoma specially early stage disease. Combined CA125 and HE4 was a more accurate predictor of ovarian malignancy than either alone.

Association of the receptor for advanced glycation end products (RAGE) -374 T/A gene polymorphism and circulating soluble RAGE with nephropathy in type 1 diabetic patients.

The binding of advanced glycation end-products (AGEs) to their receptor (RAGE) may play an important role in the development of diabetic vascular complications. Circulating soluble RAGE (sRAGE) reflects tissue RAGE expression. We examined circulating sRAGE and RAGE -374 T/A gene promoter polymorphism in type 1 diabetic patients and explored their possible associations with the development of nephropathy. Fifty diabetic patients with disease duration >10 years and 20 age, sex and body mass index (BMI) matched healthy controls were included in the study. Diabetic patients were subdivided into 23 patients without nephropathy and 27 with nephropathy. All the studied individuals were subjected to the following investigations: fasting glucose, HbA1c, serum creatinine, lipid profile, albuminuria and sRAGE levels. The -374 T/A RAGE gene polymorphism was studied by PCR amplification and restriction fragment length polymorphism (RFLP) analysis. Our study reported significant increase in sRAGE in diabetic patients compared to controls and in diabetic patients with nephropathy compared to those without nephropathy (P < 0.001). sRAGE was significantly correlated with HbA1c, creatinine, albuminuria and atherogenic lipid profile. There were significant increase in the frequency of RAGE -374 A allele (T/A and/or A/A genotypes) in diabetic patients with nephropathy compared to those without nephropathy and control groups (P < 0.01). A allele was a risk factor for diabetic nephropathy (OR 2.36 & 95% CI 1.1-5.6). RAGE -374 A allele was associated with increased sRAGE levels, hypertension and increased creatinine concentration in diabetic patients. This study points to the possible role of sRAGE as a marker of early nephropathy in diabetic patients. Early testing for the RAGE gene -374 T/A could have merit in predicting risk of diabetic nephropathy later in life.