Browsing by Author "Guzel, Esra"

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Differential Expression of Stem Cell Markers and ABCG2 in Recurrent Prostate Cancer
(Wiley-Blackwell, 2014) Guzel, Esra; Karatas, Omer F.; Duz, Mehmet B.; Solak, Mustafa; Ittmann, Michael; Ozen, Mustafa
BACKGROUND. Prostate cancer (PCa) is the second most common tumor type related to mortality in males in the developed countries. Studies have demonstrated that therapeutic tools mostly ineffective to give positive outcome especially for PCa. Cancer stem cells are composed of a small cell population, which are supposed to have roles in tumorigenesis, metastasis, and tumor recurrence after chemo-radiotherapy. The aim of this research is to investigate expressions of stem cell markers in recurrent PCa and non-recurrent PCa tumors as well as in adjacent normal prostate tissues. METHODS. We compared the expression of important sternness regulators like SOX2, OCT4, KLF4, and ABCG2 in recurrent, non-recurrent PCa and adjacent normal tissue samples using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS. Our results demonstrated that SOX2 and OCT4 are strongly overexpressed in PCa samples. Recurrent PCa samples are markedly positive for stem cell markers SOX2, OCT4, and KLF4. Furthermore, non-recurrent PCa samples presented low levels of ABCG2, a multidrug resistance protein, compared to both normal and recurrent samples, which might be associated with chemo-sensitivity. CONCLUSIONS. Enhanced expression of ABCG2 and stem cell markers including SOX2, OCT4, and KLF4 in the recurrent PCa tissues postulates the suggestion that enrichment for cells with stem cell characteristics in these tissues might be playing a critical role for chemoresistance and recurrence of cancer. (C) 2014 Wiley Periodicals, Inc.
Identification of miR139 as a Saliva Biomarker for Tongue Squamous Cell Carcinoma: A Pilot Study
(Springer, 2016) Duz, Mehmet Bugrahan; Karatas, Omer Faruk; Guzel, Esra; Turgut, Nesrettin Fatih; Yilmaz, Mehmet; Creighton, Chad J.; Ozen, Mustafa
Of all human oral carcinomas, 41 % are localized to the tongue. Despite considerable improvements in both diagnosis and treatment, tongue squamous cell carcinoma (TSCC) has remained one of the most lethal types of cancer. Here, we aimed at identifying a salivary microRNA (miRNA) expression signature specific for TSCC patients. To identify putative diagnostic biomarkers, we compared the miRNA expression profiles of saliva samples from three TSCC patients and four healthy control individuals using an Agilent miRNA microarray platform (V19). Three of the differentially expressed miRNAs identified were selected for further validation using quantitative reverse-transcription PCR (qRT-PCR) in saliva samples from 25 TSCC patients and 25 healthy control individuals. Through microarray-based expression profiling, we found that 419 miRNAs were deregulated in the saliva samples from the TSCC patients compared to those from the healthy control individuals tested. Subsequent qRT-PCR analysis revealed that the expression level of miR-139-5p was significantly reduced in the TSCC validation samples compared to the controls. Further analysis of post-operative saliva samples derived from TSCC patients revealed that the miR-139-5p expression levels had turned back to normal again. In addition, we found that miR-139-5p exhibited enough power to discriminate pre-operative TSCC patients from both normal individuals (AUC: 0.805) and post-operative TSCC patients (AUC: 0.713), thereby underscoring its diagnostic potential. From our results we conclude that saliva can be used as a feasible source for routine TSCC diagnostics and that miR-139-5p may serve as a potential biomarker for early TSCC detection.
Identification of miRNAs Differentially Expressed in Prostatic Secretions of Patients with Prostate Cancer
(Wiley, 2015) Guzel, Esra; Karatas, Omer F.; Semercioz, Atilla; Ekici, Sinan; Aykan, Serdar; Yentur, Serhat; Ozen, Mustafa
Prostate cancer (PCa) is one of the leading causes of cancer deaths in men. Since there are limited treatment options available for the advanced tumors, there is an urgent need for novel diagnostic tools for PCa. Prostate secretion samples (PSS) from 23 PCa and 25 benign prostate hyperplasia (BPH) patients were obtained from Urology Department of Bagcilar Educational and Research Hospital (Istanbul). MicroRNA (miRNA) profiling of eight PSS (four from BPH, four from PCa patients) was performed using microarray. Four of significantly deregulated miRNAs were further confirmed using quantitative reverse-transcription PCR (qRT-PCR). Statistical analysis was performed using Student's t-test. ROC curves were plotted with SPSS-15.0. In this study, we aimed to identify a miRNA expression signature that could be used to distinguish PCa from BPH. MiRNA profiling of four PCa and four BPH patients with microarray revealed that miR-361-3p, miR-133b and miR-221 were significantly downregulated and miR-203 was upregulated in PSS of PCa patients. Further qRT-PCR analysis confirmed the altered expressions of these four miRNAs in PSS of 23 PCa and 25 BPH patients. Four miRNAs, together and individually have much power (AUC; 0.950) than PSA has (AUC; 0.463) to discriminate PCa from BPH patients. We have shown for the first time in the literature the presence of miRNAs in the PSS. We suggest PSS as a powerful non-invasive source for evaluation of prognosis in PCa, since prostate massages can be easily applied during routine examination. Our results showed that certain differentially expressed miRNAs in PSS could be used as diagnostics markers. What's new? The association of microRNAs (miRNAs) with cancer initiation, progression, and metastasis has fueled increasing interest in their potential as diagnostic and therapeutic markers. The current study aimed to identify an miRNA expression signature that could be used to distinguish prostate cancer from benign prostatic hyperplasia by using prostate secretions obtained from patients. MiRNAs were found to be present in the prostate secretion samples, with altered expression detected for four miRNAs in particular. The findings suggest that certain miRNAs may be powerful tools for aiding prostate cancer diagnosis.
Microrna Profiling in Lymphocytes and Serum of Tyrosinemia Type-I Patients
(Springer, 2013) Karatas, Omer Faruk; Guzel, Esra; Karaca, Ender; Sevli, Serhat; Soyucen, Erdogan; Yuksel, Adnan; Ozen, Mustafa
Tyrosinemia type-I results from lack of fumarylacetoacetate hydrolase (FAH), which is a liver enzyme and also shown to be present in lymphocytes, fibroblasts, and cultured amniotic fluid cells. In young infants, symptoms of untreated Tyrosinemia type-I are restricted to severe liver involvement. Later in the first year; however, it is known to be present with liver and renal tubular dysfunction associated with growth failure and rickets. MicroRNAs are small regulatory RNAs that function post-transcriptionally. They target commonly 3'-UTR of the mRNAs and inhibit protein expression by either blocking the synthesis or causing degradation of the mRNAs. MiRNA deregulation was observed in a variety of pathologic conditions but their roles in metabolic diseases were remained unsolved. We studied 6 patients with classical phenotypes of Tyrosinemia type-I. To identify possible miRNAs targeting FAH transcripts, microarray profiling of 961 miRNAs for lymphocytes and serum is performed. Computational algorithms are used for prediction of putative mRNA-miRNA interactions. A number of deregulated miRNAs, targeting the non-conserved sites on FAH transcripts were found. Besides, there are some miRNAs that are similarly altered both in lymphocytes and serum, possibly contributing to the disease phenotype. Since miRNAs may have an active role in the enzymatic pathway of tyrosine catabolism, characterizing miRNA profile in fibroblasts of tyrosinemia patients is also important because miRNAs would have distinctive role in disease pathogenesis and they are promising for future therapeutic studies.
Micrornas as Prognostic Markers in Prostate Cancer
(Wiley, 2019) Suer, Ilknur; Guzel, Esra; Karatas, Omer F.; Creighton, Chad J.; Ittmann, Michael; Ozen, Mustafa
Background Prostate cancer (PCa) is the most commonly diagnosed malignancy in men who are especially over the age of 50 years in the western countries. Currently used therapeutic modalities mostly fail to give positive clinical outcomes and nearly 30% of the PCa patients eventually develop clinical recurrence. Therefore, understanding the underlying mechanisms of PCa progression is of paramount importance to help determining the course of disease. In this study, we aimed at profiling the differentially expressed microRNAs in recurrent PCa samples. Methods We profiled the microRNA expression of 20 recurrent and 20 non-recurrent PCa patients with microRNA microarray, and validated the differential expression of significantly deregulated microRNAs in 40 recurrent and 39 non-recurrent PCa specimens using quantitative reverse-transcription PCR (qRT-PCR). Data were statistically analyzed using two-sided Student's t-test, Pearson Correlation test, Receiver operating characteristic (ROC) analysis. Results Our results demonstrated that a total of 682 probes were significantly deregulated in recurrent versus non-recurrent PCa specimen comparison. Among those, we confirmed the significant downregulation of miR-424 and upregulation of miR-572 with further qRT-PCR analysis in a larger sample set. Further ROC analysis showed that these microRNAs have enough power to distinguish recurrent specimens from non-recurrent ones on their own. Conclusions Here, we report that differential expression of miR-424 and miR-572 in recurrent PCa specimens can serve as novel biomarkers for prediction of PCa progression.
miR1 and miR133b Are Differentially Expressed in Patients with Recurrent Prostate Cancer
(Public Library Science, 2014) Karatas, Omer Faruk; Guzel, Esra; Suer, Ilknur; Ekici, Isin D.; Caskurlu, Turhan; Creighton, Chad J.; Ozen, Mustafa
Prostate cancer (PCa) is currently the most frequently diagnosed malignancy in the western countries. It is more prevalent in older men with 75% of the incident cases above 65 years old. After radical prostatectomy, approximately 30% of men develop clinical recurrence with elevated serum prostate-specific antigen levels. Therefore, it is important to unravel the molecular mechanisms underlying PCa progression to develop novel diagnostic/therapeutic approaches. In this study, it is aimed to compare the microRNA (miRNA) profile of recurrent and non-recurrent prostate tumor tissues to explore the possible involvement of miRNAs in PCa progression. Total RNA from 41 recurrent and 41 non-recurrent PCa tissue samples were used to investigate the miRNA signature in PCa specimens. First of all, 20 recurrent and 20 non-recurrent PCa samples were profiled using miRNA microarray chips. Of the differentially expressed miRNAs, miR-1, miR-133b and miR-145* were selected for further validation with qRT-PCR in a different set of 21 recurrent and 21 non-recurrent PCa samples. Data were statistically analyzed using two-sided Student's t-test, Pearson Correlation test, Receiver operating characteristic analysis. Our results demonstrated that miR-1 and mir-133b have been significantly downregulated in recurrent PCa specimens in comparison to non-recurrent PCa samples and have sufficient power to distinguish recurrent specimens from non-recurrent ones on their own. Here, we report that the relative expression of miR-1 and mir-133b have been significantly reduced in recurrent PCa specimens in comparison to non-recurrent PCa samples, which can serve as novel biomarkers for prediction of PCa progression.
miR221 as a Pre- and Postoperative Plasma Biomarker for Larynx Cancer Patients
(Wiley, 2015) Yilmaz, Seda Salman; Guzel, Esra; Karatas, Omer Faruk; Yilmaz, Mehmet; Creighton, Chad J.; Ozen, Mustafa
Objective: In order to identify a plasma microRNA (miRNA) signature of larynx cancer (LCa), we examined miRNAs profile of plasma samples obtained from 30 LCa patients (preoperative and postoperative serum samples) and 30 healthy controls. Study Design: Basic science research study. Methods: MicroRNA profiling of eight plasma samples (four from preoperative, four from control individuals) were performed using miRNA microarray. Two of the significantly deregulated miRNAs were selected for further confirmation in the remaining samples using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results: Microarray profiling and qRT-PCR analysis showed that miR-221 was upregulated in LCa plasma samples. Further qRT-PCR analysis demonstrated that miR-221 was at normal levels in postoperative plasma samples. Conclusions: Plasma miR-221 may have a potential as a novel diagnostic/prognostic marker and might be considered as a therapeutic target in LCa.
Overexpression of miR145 Inhibits Proliferation of Prostate Cancer Cells and Reduces Sox2 Expression
(Taylor & Francis Inc, 2015) Ozen, Mustafa; Karatas, Omer Faruk; Gulluoglu, Sukru; Bayrak, Omer Faruk; Sevli, Serhat; Guzel, Esra; Ittmann, Michael
We aimed to perform functional analysis of miR-145-5p in prostate cancer (PCa) cells and to identify targets of miR-145-5p for understanding its role in PCa pathogenesis. PC3, DU145, LNCaP PCa, and PNT1a nontumorigenic prostate cell lines were utilized for functional analysis of miR-145-5p. Its overexpression caused inhibition of proliferation through apoptosis and reduced migration in PCa cells. SOX2 expression was significantly decreased in both mRNA and protein level in miR-145-5p-overexpressed PCa cells. We proposed that miR-145-5p, being an important regulator of SOX2, carries a crucial role in PCa tumorigenesis.
The Role of ATP-Binding Cassette Transporter Genes in the Progression of Prostate Cancer
(Wiley, 2016) Karatas, Omer F.; Guzel, Esra; Duz, Mehmet B.; Ittmann, Michael; Ozen, Mustafa
BACKGROUNDProstate cancer (PCa) is the most commonly diagnosed neoplasm and the second leading cause of cancer-related death among men in developed countries. There is no clear evidence showing the success of current screening tests in reducing mortality of PCa. In this study, we aimed to profile expressions of nine ABC transporters, ABCA5, ABCB1, ABCB6, ABCC1, ABCC2, ABCC3, ABCC5, ABCC10, and ABCF2, in recurrent, non-recurrent PCa and normal prostate tissues. METHODSA total of 77 (39 recurrent, 38 non-recurrent) radical prostatectomy and 20 normal prostate samples, obtained from Baylor College of Medicine Prostate Cancer program, were included into the study and divided into two independent groups as test and validation sample sets. Differential expression of selected ABC transporters was assessed using quantitative real-time PCR (qRT-PCR). Pearson's correlation test, receiver operating characteristics (ROC) analysis and Kaplan-Meier test were used for statistical analysis. RESULTSQRT-PCR results demonstrated the elevated expression of ABCA5, ABCB1, ABCB6, ABCC1, and ABCC2 as well as reduced expression of ABCC3 in PCa samples compared to normal prostate tissues. In addition, we found deregulation of ABCB1, ABCB6, ABCC3, and ABCC10 in recurrent PCa samples and validated differential expression of ABCB6, ABCC3, and ABCC10 in recurrent PCa compared to non-recurrent PCa. Pearson's correlation, ROC and Kaplan-Meier analysis revealed the power of these three ABC transporters for estimating prognosis of PCa. CONCLUSIONSWe demonstrated differential expression of ABC transporters both in tumor versus normal and recurrent versus non-recurrent comparisons. Our data suggest ABCB6, ABCC3, and ABCC10 as valuable predictors of PCa progression. Prostate 76:434-444, 2016. (c) 2015 Wiley Periodicals, Inc.