The Impact of Cell-free Plasma DNA on Metastatic and Nonmetastatic Prostate Cancer.

Intorductuion: Increased cell-free DNA (cfDNA) is observed in many diseases such as cancer, myocardial infarction, and autoimmune diseases. It has the ability to alter the receptor cell phenotype, triggering events related to malignant transformation. AIMS: Our study aims at assessing the use of cell-free plasma DNA in the diagnosis of metastatic and non-metastatic prostate cancer. METHODS: The study included 180 subjects who were classified into four groups: Group I (GI) included 50 perfect health subjects as the control group, Group II (GII) included 40 patients with prostatitis, group III (GIII) included 40 patients with benign prostatic hyperplasia (BPH) and Group IV (GIV) included 50 patients with pre-operative prostate cancer (PC). Evaluation of the plasma level of circulating cell-free DNA by real-time PCR and measurement of total PSA (tPSA) and free to total PSA percent (f/tPSA%) were carried out for all groups. RESULTS: Our study revealed that the level of tPSA was significantly higher in prostate cancer patients, while levels of f/t PSA were found to be significantly lower. The level of cfDNA was significantly higher in prostate cancer patients (399.9±88.6ng/ul) when compared to that of group I (12.1±1.5ng/ul) (p<0.01), group II (14.7±2.4 ng/ul) (p<0.01), and group III (26.6±45.6 ng/ul) (p<0.01) respectively. CONCLUSION: There was a statistically significant difference in yields of cfDNA between metastatic and non-metastatic groups (P=0.03) with a higher level in the metastatic group.

The Influence of rs1859168 Polymorphism on Serum Expression of HOTTIP and Its Target miR-615-3p in Egyptian Patients with Breast Cancer.

BACKGROUND: Polymorphisms of long noncoding RNAs are lately documented as hazardous factors for the development of numerous tumors. Furthermore, the evaluation of noncoding RNAs has emerged as a novel detector of breast cancer patients. We aimed to genotype the HOXA transcript at the distal tip (HOTTIP) rs1859168 and assess its relationship with the levels of the serum HOTTIP and its target miR-615-3p in patients with breast cancer (BC). METHODS: One hundred and fifty-one patients with BC, 139 patients with fibroadenoma (FA), and 143 healthy participants were incorporated into the current study. The genotyping of rs1859168 and the measurements of the HOTTIP and miR-615-3p levels were assessed using quantitative real-time PCR. RESULTS: We revealed a significant association between each of the CC genotypes, C allele, dominant and recessive models, and the increased risk of BC (p = 0.013, p < 0.001, p < 0.001, and p < 0.001, respectively) relative to the healthy controls. Similarly, the CC genotype, C allele, and recessive model were observed to be related to the increased incidence of BC with respect to FA (p < 0.001 for all). A significant upregulation of HOTTIP and a marked decrease of miR-615-3p were verified in patients with BC compared to each of the healthy individuals, patients with FA, and the non-BC group (healthy subjects + FA) (p < 0.001 for all). A significant negative correlation was demonstrated between the expression of HOTTIP and miR-615-3p in the serum of patients with BC. The HOTTIP expression was upregulated, while that of miR-615-3p was downregulated in patients with BC who carried the CC genotype with respect to those who carried the AA or AC genotypes (p < 0.05 for all). CONCLUSIONS: The genetic variants of rs1859168 are linked to an increased susceptibility to BC. Moreover, HOTTIP and miR-615-3p may be used as novel indicators and targets for the treatment of patients with BC.

Association Between rs1859168/HOTTIP Expression Level and Colorectal Cancer and Adenomatous Polyposis Risk in Egyptians.

LncRNA HOTTIP is a new lncRNA that is strictly linked to the susceptibility, growth, propagation, and prognosis of several human cancers together with colorectal cancer. lncRNA HOTTIP rs1859168 may confer colorectal cancer susceptibility through regulating its gene expression level. To elucidate its role in colorectal cancer risk, we genotyped rs1859168 A>C and measured serum HOTTIP expression level in colorectal cancer, adenomatous polyposis patients and controls by real-time polymerase chain reaction. The results displayed that rs1859168 A>C single-nucleotide polymorphism is a risk factor for colorectal cancer among adenomatous polyposis patients and controls, AC versus CC genotypes [adjusted odds ratio (OR) = 2.256, 95% confidence interval (CI) = 1.316-3.868, P = 0.003] when compared with controls and (adjusted OR = 9.521, 95% CI = 3.330-27.217, P < 0.0001) when compared with adenomatous polyposis. Serum HOTTIP was upregulated in the colorectal cancer group when compared with adenomatous polyposis or controls [median (interquartile range) = 3.64 (2.46-5.02) (P < 0.0001)]. A significant difference in serum HOTTIP was found to be associated with different rs1859168 genotypes. rs1859168 A>C and higher serum HOTTIP were significantly associated with distant metastasis, lymph nodes metastasis, and grade III of colorectal cancer. Both rs8159168 and high HOTTIP confer increased risk for colorectal cancer development. [Figure: see text].

Association analyses of a genetic variant in long non-coding RNA MEG3 with breast cancer susceptibility and serum MEG3 expression level in the Egyptian population.

BACKGROUND: LncRNA MEG3 rs7158663 has been shown to confer cancer susceptibility, maybe through altering its gene expression level. OBJECTIVE: We aimed to weigh the effect of rs7158663 on MEG3 serum level and breast cancer susceptibility. METHODS: We genotyped rs7158663 G > A and measured serum MEG3 in 150 breast cancer, 95 fibroadenoma , and 154 controls by the TaqMan method. RESULTS: The presence of rs7158663 G > A is a risk factor for breast cancer among fibroadenoma patients and controls, AA vs. GG genotypes (OR = 6.320, 95% CI = 2.587-15.439, P< 0.0001 when compared to controls and OR = 10.825, 95% CI = 1.929-60.742, P= 0.007 when compared to fibroadenoma). Decreased serum MEG3 was observed in breast cancer group when compared with fibroadenoma and/or controls [median (IQR) = 0.43 (0.27-0.55)] (P< 0.0001). However, increased serum MEG3 was noted in fibroadenoma group when compared with controls (P< 0.0001). A significance decreased serum MEG3 was found to be associated with mutant A allele than with wild G allele (P< 0.0001). The results showed that rs7158663 and lower MEG3 were significantly associated with patients with higher TNM staging and larger tumor size > 5 cm. CONCLUSION: The presence of both rs7158663 and low MEG3 are diagnostic and unfavorable prognostic factors for BC patients.

Association between LINC00657 and miR-106a serum expression levels and susceptibility to colorectal cancer, adenomatous polyposis, and ulcerative colitis in Egyptian population.

Colorectal cancer (CRC) represented the second cause of mortality among cancer patients. Long noncoding RNAs and microRNAs (miRNAs) serve as noninvasive biomarkers for CRC surveillance and introduce new therapeutic approaches. LINC00657 and miR-106a expression levels play a pivotal role in CRC. This study included 190 Egyptian subjects, and the expression levels of LINC00657 and miR-106a in serum were measured by using quantitative real-time polymerase chain reaction. We found that upregulation of LINC00657 and downregulation of miR-106a are significantly associated with the development of CRC. Also, a positive correlation was detected between their serum levels. In addition, serum LINC00657 can distinguish adenomatous polyposis (AP) patients and/or ulcerative colitis (UC) patients from controls. Also the miRNA-106a expression level discriminates AP but not UC from healthy individuals. Our study cited new diagnostic biomarkers for CRC, AP, and UC among Egyptians in addition to be noninvasive screening tools for CRC in both healthy subjects and those having precancerous lesions. © 2019 IUBMB Life, 71(9):1322-1335, 2019.

Association of SPARC gene polymorphisms rs3210714 and rs7719521 with VEGF expression and utility of Nottingham Prognostic Index scoring in breast cancer in a sample of Egyptian women.

Breast cancer is the most common malignancy in women. To our knowledge, there is no single study conducted on the role of secreted protein acidic and rich in cysteine (SPARC) gene polymorphism in breast cancer risk or prognosis. The present study aims to investigate the probable role of SPARC genetic polymorphisms in development of breast cancer; their correlation with immunohistochemical expression of VEGF; and their association with breast cancer prognosis in the Egyptian population. The study sample included 238 Egyptian females who were divided into two groups: breast cancer group (118 patients) and healthy control group (120 subjects). SPARC gene single nucleotide polymorphisms rs3210714 and rs7719521 were genotyped. Allelic and genotypic frequencies were determined in both groups and association with ductal breast carcinoma, clinicopathological and prognostic characters were determined. For SPARC rs3210714, a significant difference was observed in the codominant model and both A and G alleles' frequencies between breast cancer patients and control group (P < 0.001). For rs7719521, a significant difference in codominant and dominant models as well as in both A and C alleles' frequencies between breast cancer and control groups (P < 0.001) was observed. A significant relation was found between SPARC rs3210714 and rs7719521, and immunohistochemical expression of VEGF (P = 0.046 and P = 0.027, respectively). SPARC rs7719521 showed a significant association with Nottingham Prognostic Index (NPI) (P = 0.032). The present study revealed that SPARC rs3210714 and rs7719521 polymorphisms are associated with breast cancer risk and its prognosis. Therefore, these SNPs may be useful in predicting the increased risk of breast cancer.