4 research outputs found
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The potential prognostic and therapeutic application of tissue and circulating microRNAs in cervical cancer
Cervical cancer (CC) is a common malignancy in women and a major cause of cancer- related mortality globally. Some novel biomarkers may enable the early diagnosis and monitoring of CC. MicroRNAs are small noncoding RNAs that control gene translation at a post transcriptional level. Hence the deregulation of these molecules can cause many diseases. There appears to be an association between aberrant miRNA expression and CC, but the molecular mechanisms involved in the development of CC remain unknown. The upregulation of some circulating miRNAs, e.g. miRNA-20a, miRNA-203, miRNA-21, miRNA-205, miRNA-218, and miR-485-5, as well as tissue specific-miRNAs, e.g. miR-7, miR-10a, miR-17-5p, miR-135b, miR-149 and miR-203 has been found in patients with CC. There is also growing evidence for the importance of miRNAs in the development of drug-resistance. This review therefore highlights recently published preclinical and clinical investigation performed on tissue-specific and circulating miRNAs, as potential biomarkers for the detection of patients at early stages of CC, in the prediction of prognosis, and monitoring of their response to therapy.
Key word: cervical cancer, CIN, MiRNA, circulating biomarker, tissue-specific biomarker, HP
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Epigenetic drug therapy in the treatment of colorectal cancer
Colorectal cancer (CRC) is one of the most common cancers with a high rate of morbidity and mortality worldwide. The incidence of CRC is similar in men and women but is distributed uniformly globally. It has been demonstrated that epigenetic alterations which may cause changes in the expression of microRNA, DNA methylation and histone acetylation that results in inheritable modifications in gene expression in colorectal epithelial cells, plays a crucial role in the development of CRC. Recently, targeting epigenetic modification has emerged as a potentially important treatment approach in CRC. The US Food and Drug Association has approved the use of some epigenetic drugs that may be able to inhibit or reverse these alterations and also enhance sensitivity to chemotherapeutic agents and radiotherapy in CRC. In this review we have summarized the recent pre-clinical and clinical trial studies investigating the therapeutic value of using epigenetic drugs as novel therapeutic approach in CRC treatment.
Keywords: epigenetic, colorectal cancer, drug, DNA methylation, histone acetylatio
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The interaction between a HSP-70 gene variant with dietary calories in determining serum markers of inflammation and cardiovascular risk
Background: The high prevalence of cardiovascular disease (CVD) globally is attributable to an interaction between environmental and genetic factors. Gene Ă— diet interaction studies aim to explore how a modifiable factor interacts with genetic predispositions. Here we have explored the interaction of a heat shock protein (HSP70) gene polymorphism (+1267A>G) with dietary intake and their possible association with serum C-reactive protein (CRP), an inflammatory marker, that is a major component of CVD risk.
Methods: HSP70 genotype was determined using a TaqMan real time PCR based method. Genetic variation of the HSP70 gene +1267A>G locus. Dietary intake was assessed using a dietary questionnaire. Serum high sensitivity (Hs) CRP and other cardiovascular risk factors were assessed by routine methods. This included coronary angioplasty to determine the presence of coronary artery stenosis.
Results: There were significant differences between serum lipid profile and Hs-CRP across the genotypes for Hsp70. The carriers of G allele had higher serum hs-CRP concentrations, compared with the AA homozygotes, with the wild genotype. Interaction analysis showed the association was modulated by total energy intake; the interaction of high energy intake with GG genotype: RERI= 0.77, AP= 0.26, S=1.6.
Conclusion: We have found a significant association between the +1267A>G variant of the HSP70 gene with cardiovascular risk factors and serum hs-CRP concentrations. It is possible that a low energy diet could ameliorate the unfavorable effects of G allele of HSP70
The Prognostic Value of ASPHD1 and ZBTB12 in Colorectal Cancer: A Machine Learning-Based Integrated Bioinformatics Approach
Introduction: Colorectal cancer (CRC) is a common cancer associated with poor outcomes, underscoring a need for the identification of novel prognostic and therapeutic targets to improve outcomes. This study aimed to identify genetic variants and differentially expressed genes (DEGs) using genome-wide DNA and RNA sequencing followed by validation in a large cohort of patients with CRC. Methods: Whole genome and gene expression profiling were used to identify DEGs and genetic alterations in 146 patients with CRC. Gene Ontology, Reactom, GSEA, and Human Disease Ontology were employed to study the biological process and pathways involved in CRC. Survival analysis on dysregulated genes in patients with CRC was conducted using Cox regression and Kaplan–Meier analysis. The STRING database was used to construct a protein–protein interaction (PPI) network. Moreover, candidate genes were subjected to ML-based analysis and the Receiver operating characteristic (ROC) curve. Subsequently, the expression of the identified genes was evaluated by Real-time PCR (RT-PCR) in another cohort of 64 patients with CRC. Gene variants affecting the regulation of candidate gene expressions were further validated followed by Whole Exome Sequencing (WES) in 15 patients with CRC. Results: A total of 3576 DEGs in the early stages of CRC and 2985 DEGs in the advanced stages of CRC were identified. ASPHD1 and ZBTB12 genes were identified as potential prognostic markers. Moreover, the combination of ASPHD and ZBTB12 genes was sensitive, and the two were considered specific markers, with an area under the curve (AUC) of 0.934, 1.00, and 0.986, respectively. The expression levels of these two genes were higher in patients with CRC. Moreover, our data identified two novel genetic variants—the rs925939730 variant in ASPHD1 and the rs1428982750 variant in ZBTB1—as being potentially involved in the regulation of gene expression. Conclusions: Our findings provide a proof of concept for the prognostic values of two novel genes—ASPHD1 and ZBTB12—and their associated variants (rs925939730 and rs1428982750) in CRC, supporting further functional analyses to evaluate the value of emerging biomarkers in colorectal cancer.</p