The emerging role of lncRNA MEG3 and MEG3 rs7158663 in hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy in Egypt. Genetic and environmental factors play a role in its development. This study explored the association between the long non-coding RNA (lncRNA) MEG3 rs7158663 polymorphism, MEG3 expression, and the risk of HCC and other clinicopathologic characteristics in an Egyptian population. PATIENTS AND METHODS: This case-control study included 114 patients with HCC and 110 healthy controls. TaqMan Real-time PCR was used to analyze lncRNA MEG3 rs7158663. Serum MEG3 expression levels were measured using RT-PCR. RESULTS: The AA, GA+AA, and A alleles were associated with increased risk for HCC (adjusted odds ratio (OR) 11.84%, 95% CI 4.07-34.45, p < 0.0001; adjusted OR 3.18, 95% CI 1.79-5.67, p < 0.0001; and adjusted OR 2.87, 95% CI 1.91-4.34, p < 0.0001, respectively). The mutant genotype and allele were linked to an increased risk in male patients and patients ≥ 50 years old. MEG3 serum expression level was downregulated in HCC patients. The rs7158663 G > A polymorphism and downregulated MEG3 were significantly associated with larger tumor size and advanced disease stage. CONCLUSIONS: MEG3 rs7158663 single nucleotide polymorphisms and downregulated lncRNA MEG3 were associated with HCC risk and may represent diagnostic and bad prognostic factors for HCC patients.

Peroxisome Proliferator-Activated Receptor Gamma in Obesity and Colorectal Cancer: the Role of Epigenetics.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that is deregulated in obesity. PPARγ exerts diverse antineoplastic effects. Attempting to determine the clinical relevance of the epigenetic mechanisms controlling the expression PPARγ and susceptibility to colorectal cancer (CRC) in obese subjects, this study investigated the role of some microRNAs and DNA methylation on the deregulation of PPARγ. Seventy CRC patients (34 obese and 36 lean), 22 obese and 24 lean healthy controls were included. MicroRNA levels were measured in serum. PPARγ promoter methylation was evaluated in peripheral blood mononuclear cells (PBMC). PPARγ level was evaluated by measuring mRNA level in PBMC and protein level in serum. The tested microRNAs (miR-27b, 130b and 138) were significantly upregulated in obese and CRC patients. Obese and CRC patients had significantly low levels of PPARγ. A significant negative correlation was found between PPARγ levels and the studied microRNAs. There was a significant PPARγ promoter hypermethylation in CRC patients that correlated to low PPARγ levels. Our results suggest that upregulation of microRNAs 27b, 130b and 138 is associated with susceptibility to CRC in obese subjects through PPARγ downregulation. Hypermethylation of PPARγ gene promoter is associated with CRC through suppression of PPARγ regardless of BMI.

Human papillomavirus (HPV) in Egyptian females: study by cytology, histopathology, colposcopy and molecular diagnosis of high risk types.

OBJECTIVES: In Northern Africa, the region Egypt belongs to, about 10.7% of women are estimated to harbour cervical human papillomavirus (HPV) infection and 78.4% of invasive cancers are attributed to HPVs 16 or 18. We aimed at comparing HPV detection by ISH-PCR tissue with other conventional available cheaper techniques, finding which of them can be relied upon in a developing country like Egypt for HPV detection. METHODS: Sixty patients were included. For them colposcopy, PAP smear, histopathology and detection of HPV using ISH PCR tissue and PCR swab were achieved. RESULTS: PCR-ISH tissue was positive in 53.33%, 46.6% were negative. Pap smear was negative in 26 cases (43.33%) and 43 cases (56.67%) were positive. LSIL with perinuclear halo represented nearly half of the positive cases (16/34; 47.05%), 10 cases were diagnosed as HSIL, 4 cases as ASCUS and 4 as AGC. Histopathology was negative in 12 (20%) cases and 48 (80%) cases were positive. CIN I and CIN I+ koliocytosis represented half of the cases (30/60) and more than half of positive cases (30/48; 62.5%). Comparing the results of pap smear, histopathology, colposcopy and PCR swab with ISH PCR tissue, highly significant results were seen with sensitivity of 87.5%, 100%, 62.5% and 56.2% respectively but the specificity were 78.6%, 42.9%, 28.6% and 100% respectively. CONCLUSION: Conventional cytology and histopathology were sensitive tests for detection of HPV. This may help for early detection of cancer cervix in a developing country like Egypt. PCR swab showed the highest specificity and the lowest sensitivity.

Expression of sirtuins 1, 6, tumor necrosis factor, and interferon-γ in psoriatic patients.

Sirtuins (SIRT) have been regarded as culprits in the pathogenesis of various diseases. Their exact role has not been explained. This study aimed to assess the expression of SIRT1, SIRT6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in psoriatic patients. Thirty psoriatic patients and 22 controls were enrolled. Clinical examination and Psoriasis Area and Severity Index (PASI) were obtained. Two skin biopsies (lesional, peri-lesional) and one from controls were obtained. Tissue levels of SIRT1, SIRT6, TNF-α, and IFN-γ were measured using ELISA. SIRT1 was significantly lower in lesional skin with gradual increase in perilesional followed by control skin (P <0.001). SIRT6, TNF-α, and IFN-γ were significantly higher in lesional than perilesional and control skin (P <0.001). Significant positive correlations were found between SIRT1 and TNF-α, IFN-γ and between SIRT6 and TNF-α in peri-lesional skin. SIRT1 and SIRT6 are potentially involved in the pathogenesis of psoriasis. Modulating their action could offer a novel therapy for such disease.

Estimation of tissue and serum lipocalin-2 in psoriasis vulgaris and its relation to metabolic syndrome.

Adipose tissue is now considered an endocrine organ secreting different cytokines known as adipocytokines. Lipocalin-2 has been recently identified as an adipokine present in the circulation, it is related to insulin resistance, obesity, atherosclerotic diseases and type 2 diabetes. Lipocalin-2 and psoriasis are assumed to be closely associated with the metabolic syndrome. The aim of the present study is to estimate the level of lipocalin-2 in the serum and tissue of psoriatic patients and to correlate these levels with markers of metabolic syndrome, CRP and disease severity. This study was done on 30 patients of psoriasis and 30 healthy controls. All patients and controls were subjected to clinical examination. Serum, tissue levels of lipocalin-2 and C-reactive protein (CRP) were measured by enzyme linked immunosorbent assay technique. Metabolic syndrome parameters including anthropometric measures, lipid profiles, blood sugar and blood pressure were studied. Patients with psoriasis showed significant association with metabolic syndrome parameters than controls. Tissue lipocalin-2 was significantly higher than serum levels in psoriasis patients. A significant difference was detected in tissue levels of lipocalin-2 and not in the serum between patients and controls. Both tissue and serum lipocalin-2 correlated with CRP. Although there was a correlation between tissue and serum levels of lipocalin-2 in patients, there was no correlation between both of them with metabolic syndrome and related disorders. Our results revealed that patients with psoriasis are at increased risk of metabolic and cardiovascular complications, tissue lipocalin-2 is more specific to psoriasis than serum lipocalin-2. Lipocalin-2 has no role in determining severity of the disease. Neither tissue nor serum lipocalin-2 conveys cardiovascular risk in psoriasis patients.

Basic fibroblast growth factor and tumour necrosis factor alpha in vitiligo and other hypopigmented disorders: suggestive possible therapeutic targets.

BACKGROUND: In healthy skin, there is a molecular microenvironment that favours the survival of melanocytes and regulates their function. Keratinocytes synthesize and secrete several cytokines that have stimulatory and inhibitory effects on melanocytes. AIM OF THE WORK: This work was conducted to evaluate the expression of basic fibroblast growth factor (bFGF) and tumour necrosis factor alpha (TNF-α) mRNA levels in lesional skin of vitiligo, hypopigmented mycosis fungoides and hypopigmented tinea versicolor. PATIENTS AND METHODS: Forty eight patients (25 vitiligo, 14 hypopigmented mycosis fungoides, 9 hypopigmented tinea versicolor) and 10 healthy controls were included. A 4 mm punch skin biopsy was taken from lesional skin of patients, and the normal skin of controls for quantitative PCR examination of TNF-α and bFGF mRNA. RESULTS: The level of TNF-α mRNA in lesional skin of the three studied disorders was significantly higher than in the control group, while the level of bFGF mRNA was significantly lower in lesional skin of the three diseases than the control skin. A significant inverse correlation was demonstrated between the mRNA levels of the two studied cytokines in vitiligo and hypopigmented MF lesions. CONCLUSION: The study's findings demonstrate that the studied hypopigmented (vitiligo, hypopigmented MF, hypopigmented TV) disorders show similar changes in their cutaneous microenvironment with increased TNF-α and decreased bFGF mRNA expression. This cytokine microenvironment change may be implicated in the pigment loss and hence these cytokines may have future therapeutic implications.

Peroxisome proliferator-activated receptor gamma, a possible culprit in mycosis fungoides: an immunohistochemical study.

BACKGROUND: It still remains debatable whether peroxisome proliferator-activated receptor gamma (PPARγ) is pro- or antineoplastic, and its exact role in mycosis fungoides (MF) remains unclear. OBJECTIVE: This prospective comparative study aimed to investigate the expression of PPARγ in MF and compare it with psoriatics and controls in a trial to deduce its possible role in MF. Also, we tried to clarify the relation between PPARγ and Bcl-2 in MF. METHODS: Twenty MF patients, 20 psoriatic patients and 20 controls were included. All participants underwent a skin biopsy, and immunohistochemical staining for both PPARγ and Bcl-2 were performed. Western blot analysis was performed for detection of both PPARγ and Bcl-2. RESULTS: The mean area per cent of PPARγ measured in the MF patients (57.1217±9.502417) was significantly higher (P<0.001) when compared with that of both the psoriatics (2.989±1.723) and controls (35.9357±8.1789). The mean area per cent of Bcl-2 in MF patients (9.3763±6.6328) was significantly higher (P<0.001) than that of both the psoriatics (2.35±1.35) and the controls (0.73105±0.5302)]. Our results were confirmed using the western blot analysis. We detected a highly significant positive correlation between the PPARγ and Bcl-2 mean area per cents in all patients. In our MF patients, both parameters were also positively correlated with the age of the patient, duration and stage of MF (P<0.05). CONCLUSION: Our data suggest a possible role for PPARγ in the pathogenesis of MF possibly through several mechanisms, one of which might be conferring upon the lymphoma cells, a survival advantage at least partially through up regulating Bcl-2.

Serum and tissue expression of transforming growth factor beta 1 in psoriasis.

BACKGROUND: In psoriasis, keratinocyte hyperplasia may be explained by imbalance of growth factors responsible for epidermal proliferation and altered metabolism of their receptors. Transforming growth factor-beta 1 (TGF-beta1) implications in the pathogenesis of psoriasis can be attributed to several mechanisms besides keratinocyte cell cycle inhibition. OBJECTIVES: To evaluate the relation between serum and tissue levels of TGF-beta1 in psoriasis and their correlation with disease parameters. PATIENTS AND METHODS: Serum and punch biopsy of involved and non-involved skin of 22 patients with psoriasis vulgaris and 10 controls were collected for quantification of TGF-beta1 by enzyme-linked immunosorbent assay kit. RESULTS: Serum level of TGF-beta1 in psoriatic patients was higher than controls in a statistically non-significant manner. Correlations between serum level of TGF-beta1 and extent of the disease (P = 0.007) and Psoriasis Area and Severity Index (PASI) score (P = 0.005) were observed. Mean tissue levels of TGF-beta1 were highest in psoriatic lesions in contrast to normal skin of psoriatic patients and healthy controls, but not statistically significant. Correlation between tissue levels of TGF-beta1 in non-involved skin and extent of the disease (P = 0.007) and PASI score (P = 0.013) was detected. Correlation was detected between levels of TGF-beta1 in psoriatic plaques and serum of patients (P = 0.035), but not between levels of TGF-beta1 in non-involved skin and serum. CONCLUSIONS: Tissue expression of TGF-beta1 in psoriasis may be affected by the stage of development of the lesion. The direct relation between TGF-beta1 in psoriatic plaques and serum imply that the mechanisms for TGF-beta1 production and release in both these compartments may be related.

Expression of insulin-like growth factor-I in lesional and non-lesional skin of patients with morphoea.

BACKGROUND: Morphoea (scleroderma) is a chronic disorder characterized by circumscribed sclerotic plaques with the hallmark of increased fibroblast activation and fibrosis. Through its effect on connective tissue cells and immune cells, insulin-like growth factor (IGF)-I has been found to play a role in some autoimmune connective tissue diseases and has been implicated in the pathogenesis of several fibrotic disorders. OBJECTIVES: To evaluate the role of IGF-I in the pathogenesis of morphoea. METHODS: The study was carried out on 15 patients with morphoea and nine healthy controls. Two 5-mm punch skin biopsies were taken from every patient (one from lesional and one from non-lesional skin) and a single biopsy was taken from the normal skin of each control. A 10-mL blood sample was also taken from each patient and control. Quantitative detection of tissue and serum levels of IGF-I was done using an enzyme-linked immunosorbent assay technique. RESULTS: IGF-I in lesional skin was significantly higher than in non-lesional and control skin (P = 0.001 and P = 0.021, respectively). Moreover, a significantly higher level of IGF-I was detected in patient serum when compared with control serum (P < 0.001). A direct significant correlation existed between lesional and non-lesional skin level (r = 0.618, P = 0.014), and between lesional skin level and Rodnan score (r = 0.538, P = 0.039). CONCLUSIONS: Despite the small sample size, this study suggests that IGF-I plays an important role in the pathogenesis of fibrosis, characteristic of morphoea. Studies on a larger number of patients with morphoea as well as on patients with systemic sclerosis are recommended. Furthermore, therapeutic trials using IGF-I antagonist (octreotide) are highly recommended in patients with morphoea.