Publications
54 results found
Kottorou A, Antonacopoulou A, Dimitrakopoulos F-I, et al., 2018, Deregulation of methylation of transcribed-ultra conserved regions in colorectal cancer and their value for detection of adenomas and adenocarcinomas, Oncotarget, Vol: 9, Pages: 21411-21428, ISSN: 1949-2553
Expression of Transcribed Ultraconserved Regions (T-UCRs) is often deregulated in cancer. The present study assesses the expression and methylation of three T-UCRs (Uc160, Uc283 and Uc346) in colorectal cancer (CRC) and explores the potential of T-UCR methylation in circulating DNA for the detection of adenomas and adenocarcinomas.Expression levels of Uc160, Uc283 and Uc346 were lower in neoplastic tissues from 64 CRC patients (statistically significant for Uc160, p<0.001), compared to non-malignant tissues, while methylation levels displayed the inverse pattern (p<0.001, p=0.001 and p=0.004 respectively). In colon cancer cell lines, overexpression of Uc160 and Uc346 led to increased proliferation and migration rates. Methylation levels of Uc160 in plasma of 50 CRC, 59 adenoma patients, 40 healthy subjects and 12 patients with colon inflammation or diverticulosis predicted the presence of CRC with 35% sensitivity and 89% specificity (p=0.016), while methylation levels of the combination of all three T-UCRs resulted in 45% sensitivity and 74.3% specificity (p=0.013). In conclusion, studied T-UCRs’ expression and methylation status are deregulated in CRC while Uc160 and Uc346 appear to have a complicated role in CRC progression. Moreover their methylation status appears a promising non-invasive screening test for CRC, provided that the sensitivity of the assay is improved.
Dimitrakopoulos F-I, Antonacopoulou A, Kottorou A, et al., 2018, NF-kB2 genetic variations are significantly associated with non-small cell lung cancer risk and overall survival, Scientific Reports, Vol: 8, Pages: 5259-5269, ISSN: 2045-2322
During the last decade, a growing number of publications implicate NF-kB2 in NSCLC pathogenesis. Here, we investigated the clinical relevance of NF-kB2 single nucleotide polymorphisms (SNPs) rs7897947, rs11574852 and rs12769316 in NSCLC and their association with NF-kB2 protein and mRNA levels. Our data show that TT (rs7897947T >G) and AA (rs12769316G >A) genotypes were strongly associated with an increased risk for NSCLC (P = 0.019 and P = 0.003, respectively). Additionally, in multivariate analysis, TT (rs7897947T >G) homozygosity was associated with worse 2- and 3-year survival rates (P = 0.030 and P = 0.028, respectively), especially among patients with stages III/IV, who had worse 2, 3 and 5-year survival (P = 0.001, P = 0.022 and P = 0.035, respectively). In chemotherapy-treated patients, TT (rs12769316G >A) homozygosity was also associated with worse 2- and 3-year survival compared to G allele carriers (P = 0.006 and P = 0.014, respectively). Furthermore, rs12769316 was correlated with survival outcome of stage I and II patients (P = 0.031 and P = 0.006, respectively). Interestingly, amongst the patients who developed metastases, A allele carriers had better 5-year survival (P = 0.020). In addition, rs12769316 was associated with NF-kB2 protein (P = 0.001) and mRNA expression (P = 0.017) as well as with tumor maximum diameter (P = 0.025). Overall, this study suggests that rs7897947 and rs12769316 are involved in NSCLC susceptibility, in treatment response and in clinical outcome.
Khwaja M, Kalofonou M, Toumazou C, 2017, A Deep Belief Network system for prediction of DNA methylation, IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE
A Deep Belief Network architecture is proposed for prediction of DNA methylation characteristics across genetic regions. The proposed system uses an image analogous visualisation of DNA methylation features through an efficient mapping model. Implementation of this method has resulted in an accurate classification of DNA methylation for multiple CpG regions identified in cancer cell lines and has been designed to address variability in patterns found in a given human cell, regardless of their function or disease state. The proposed method is compared to time-tested supervised learning algorithms that include Support Vector Machine and Random Forest classifiers and has been validated using data from cancer cell lines. Using documented features, it achieves differentiation of DNA methylation states, while predicting distinct features with an average value of sensitivity 92%, specificity 99%, accuracy 95% and Matthew's Correlation Coefficient 0.91. The feature set coupled with the deep learning model makes the system efficient for DNA methylation prediction, while being independent of the data set used.
Moser N, Rodriguez-Manzano J, Yu LS, et al., 2017, Live demonstration: A CMOS-based ISFET array for rapid diagnosis of the Zika virus, ISSN: 0271-4310
We demonstrate a diagnostics platform which integrates an ISFET array and a temperature control loop for isothermal DNA detection. The controller maintains a temperature of 63°C to perform nucleic acid amplification which is detected by the on-chip sensors. The 32×32 ISFET array is first calibrated to cancel trapped charge and then measures the change in the pH of the reaction. The sensor data is sent to a microcontroller and the reaction is monitored in real-time using a MATLAB interface. Experiments confirm a change of 0.9 pH when tested for the presence of RNA associated with the Zika virus.
Kottorou A, Antonacopoulou A, Dimitrakopoulos F, et al., 2017, Deregulation of methylation of transcribed-ultra conserved regions in colorectal cancer and their diagnostic and prognostic value, ASCO 2017, Publisher: American Society of Clinical Oncology, Pages: e15130-e15130
Background: Expression of Transcribed Ultra Conserved Regions (T-UCRs) is often deregulated in cancer. We investigated the role of three T-UCRs (Uc160, Uc283 and Uc346) in colorectal adenocarcinomas and their prognostic and diagnostic value. Methods: Expression and methylation levels of the T-UCRs were assessed in neoplastic and paired non-malignant fresh frozen (FF) tissue specimens from 64 colorectal cancer (CRC) patients, as well as in 6 FF adenoma tissue specimens. In addition, T-UCR methylation levels were assessed in FFPE tumor tissues from 80 CRC patients and in plasma from 161 patients (50 CRC, 59 adenoma patients, 40 healthy subjects and 12 patients with colon inflammation or diverticulosis). Results: Expression levels of all three T-UCRs were lower in neoplastic, compared to non-malignant tissues, although at a statistically significant level only for Uc160 (p< 0.001). Also, methylation levels of Uc160, Uc283 and Uc346 were higher in tumors compared to non-malignant tissues (p< 0.001, p= 0.001 and p= 0.004 respectively). Tissue methylation levels of Uc160 were associated with TTP (p= 0.017). The combination of Uc283 and Uc346 methylation levels was related to OS, however without reaching statistical significance (p= 0.066). Methylation status of Uc160 and Uc346 in plasma differed significantly among the four patient groups with CRC patients exhibiting the higher levels. Moreover, a strong correlation was found between Uc160 plasma methylation levels and adenoma or adenocarcinoma size and lymph node infiltration (p< 0.001 and p= 0.024 respectively). When methylation status was used to predict if a subject has CRC, sensitivity and specificity were 35% and 89% respectively, while the values changed to 45% and 74.3% respectively when we combined the sum of the three T-UCR plasma methylation levels. For adenomas, the combination of Uc160 and Uc346 plasma methylation displayed 30.2% (sensitivity) and 80.7% (specificity). Conclusions: T-UCR expression an
Koutsos A, Kalofonou M, Sohbati M, et al., 2016, Epigenetic-IC: A fully integrated sensing platform for epigenetic reaction monitoring, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, Pages: 325-328, ISSN: 2379-447X
This paper presents a pH-based System-on-Chip DNA methylation quantification platform for real time monitoring of DNA methylation ratio in target genes. The architecture forms a novel autonomous system, capable of providing diagnostic information on the progression of a disease, notably cancer. The system is equipped with drift and trapped charge compensation schemes based on differential measurements and an auto-calibration algorithm. The simulated system in 0.35μm CMOS technology achieves a power consumption of 0.997mW, with a DNA methylation ratio output sensitivity of 0.1%. The ISFET-based detection platform occupies a total of 901um2 and allows the calculation of DNA methylation ratio in pH-monitored DNA methylation based reactions.
Sakellakis M, Koutras A, Pittaka M, et al., 2016, Identification of a seasonal pattern to brain metastases, Neuropsychiatric Disease and Treatment, Vol: 12, Pages: 609-610, ISSN: 1178-2021
Dimitrakopoulos F-ID, Antonacopoulou AG, Kottorou A, et al., 2015, Variant of BCL3 gene is strongly associated with five-year survival of non-small-cell lung cancer patients, Lung Cancer, Vol: 89, Pages: 311-319, ISSN: 0169-5002
ObjectivesBCL3, a known atypical IκB family member, has been documented to be upregulated in hematological malignancies and in some solid tumors, functioning as a crucial player in tumor development. Recently, rs8100239, a tag-Single Nucleotide Polymorphism (SNP) in BCL3 (T > A) has been identified, but there are no data regarding its involvement in non-small-cell lung cancer (NSCLC) initiation and progression.Materials and methodsTo study the possible association of BCL3 with NSCLC, 268 patients and 279 healthy controls were genotyped for rs8100239. Moreover, BCL3 protein expression was also investigated in 112 NSCLC cases through an immunohistochemical analysis.ResultsNSCLC patients with AA genotype displayed significantly worse prognosis compared to T allele carriers (P < 0.001), who had less frequent intermediate nuclear BCL3 expression (P = 0.042). In addition, overexpression of BCL3 was detected in tumor specimens, compared to normal tissue (P < 0.001). Furthermore, BCL3 protein levels were associated with five-year survival (P =0.039), maximum diameter of lesion (P = 0.012), grade (P = 0.002) and relapse frequency (P = 0.041).ConclusionsThe present study is the first to show a relationship between the genetic variation rs8100239 of BCL3 and cancer patients’ survival. It also represents the first quantitative evaluation of BCL3 expression in NSCLC. Our findings indicate that rs8100239 may be considered as a novel prognostic indicator, demonstrating also the overexpression of BCL3 protein in NSCLC and implicating this pivotal molecule in the pathogenesis of NSCLC.
Koutras A, Sakellakis M, Makatsoris T, et al., 2015, Identification of a seasonal pattern to brain metastases., 2015 ASCO Annual Meeting, Publisher: American Society of Clinical Oncology, Pages: e12627-e12627, ISSN: 1527-7755
Giannopoulou E, Siatis KE, Metsiou D, et al., 2015, The inhibition of aromatase alters the mechanical and rheological properties of non-small-cell lung cancer cell lines affecting cell migration, BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, Vol: 1853, Pages: 328-337, ISSN: 0167-4889
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- Citations: 17
Kalofonou M, Toumazou C, 2014, Early screening of breast cancer recurrence by monitoring DNA methylation based biomarkers using semiconductor technology, MEC Annual Meeting and Bioengineering14, Cancer Engineering and Technologies
Breast cancer is one of the most common cancer types in women, with 1 in 8 women having a lifetime risk of incidence. From the cases of primary breast cancer, more than 30% of diagnosed and treated cases will most likely lead to a metastasis, also known as cancer recurrence, within a period of 5-15 years from time of first diagnosis, dependent on the aggressiveness and rate of disease progression. From the stage of first detection of primary breast cancer to the point of a metastatic recurrence, certain tumour-specific genetic and epigenetic changes occur. The use of epigenetic markers, specifically DNA methylation, as a biomarker for cancer has shown great potential due to its role in the initiation, progression and recurrence of the disease. Given that the time of the event of a metastasis can vary from the moment of initial diagnosis, the use of markers that could monitor tumour progression by detecting tumour-specific DNA methylation based changes would provide significant insight in estimating the risk of recurrence, so that the right therapy is being addressed at the right time, in a more personalised way. Current screening methods of breast cancer have shown that more newly developed/recurred breast cancer cases can now be diagnosed but with the risk of more false-positive findings which could further lead to unnecessary treatment due to the possible misinterpretation of the imaging result (low/high risk lesions). Studies have shown that DNA methylation patterns found in blood can be used as reliable markers for distinguishing breast cancer patients from healthy subjects as well as for assessing the progression of breast cancer after therapy. Detection of DNA methylation changes could therefore offer a very promising alternative approach to early screening of breast cancer recurrence, providing with a more individualised clinical assessment and management of cancer as a chronic disease. A Point-of-Care system using the methylation profile of carefully selecte
Kalofonou M, Toumazou C, 2014, Early screening of breast cancer recurrence by monitoring DNA methylation based biomarkers using semiconductor technology, Launch of Medical Engineering Centres Annual Meeting and Bioengineering14 (MECbioeng14), Cancer Engineering and Technologies
Breast cancer is one of the most common cancer types in women, with 1 in 8 women having a lifetime risk of incidence. From the cases of primary breast cancer, more than 30% of diagnosed and treated cases will most likely lead to a metastasis, also known as cancer recurrence, within a period of 5-15 years from time of first diagnosis, dependent on the aggressiveness and rate of disease progression. From the stage of first detection of primary breast cancer to the point of a metastatic recurrence, certain tumour-specific genetic and epigenetic changes occur. The use of epigenetic markers, specifically DNA methylation, as a biomarker for cancer has shown great potential due to its role in the initiation, progression and recurrence of the disease. Given that the time of the event of a metastasis can vary from the moment of initial diagnosis, the use of markers that could monitor tumour progression by detecting tumour-specific DNA methylation based changes would provide significant insight in estimating the risk of recurrence, so that the right therapy is being addressed at the right time, in a more personalised way. Current screening methods of breast cancer have shown that more newly developed/recurred breast cancer cases can now be diagnosed but with the risk of more false-positive findings which could further lead to unnecessary treatment due to the possible misinterpretation of the imaging result (low/high risk lesions). Studies have shown that DNA methylation patterns found in blood can be used as reliable markers for distinguishing breast cancer patients from healthy subjects as well as for assessing the progression of breast cancer after therapy. Detection of DNA methylation changes could therefore offer a very promising alternative approach to early screening of breast cancer recurrence, providing with a more individualised clinical assessment and management of cancer as a chronic disease. A Point-of-Care system using the methylation profile of carefully selecte
Kalofonou M, Toumazou C, 2014, A Low Power Sub-μW Chemical Gilbert Cell for ISFET Differential Reaction Monitoring, IEEE Transactions on Biomedical Circuits and Systems, Pages: 1-1, ISSN: 1932-4545
This paper presents a low power current-mode method for monitoring differentially derived changes in pH from ion-sensitive field-effect transistor (ISFET) sensors, by adopting the Chemical Gilbert Cell. The fabricated system, with only a few transistors, achieves differential measurements and therefore drift minimisation of continuously recorded pH signals obtained from biochemical reactions such as DNA amplification in addition to combined gain tunability using only a single current. Experimental results are presented, demonstrating the capabilities of the front-end at a microscopic level through integration in a lab-on-chip (LoC) setup combining a microfluidic assembly, suitable for applications that require differential monitoring in small volumes, such as DNA detection where more than one gene needs to be studied. The system was designed and fabricated in a typical 0.35 μm CMOS process with the resulting topology achieving good differential pH sensitivity with a measured low power consumption of only 165 nW due to weak inversion operation. A tunable gain is demonstrated with results confirming 15.56 dB gain at 20 nA of ISFET bias current and drift reduction of up to 100 times compared to a single-ended measurement is also reported due to the differential current output, making it ideal for robust, low-power chemical measurement.
Kalofonou M, Toumazou C, 2014, An ISFET based analogue ratiometric method for DNA methylation detection, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, Pages: 1832-1835, ISSN: 0271-4302
This paper presents the concept of a ratiometric approach for DNA methylation detection using the “Methylation Cell” for the indication of epigenetic abnormalities related to cancer. The “Methylation Cell” allows real-time detection of pH signals resulting from DNA based reactions using ISFET sensors, performing continuous computation of the ratio of DNA methylation, giving a discrete output signal when DNA methylation exceeds a certain predefined percentage. Fabricated in a typical 0.35μm CMOS process, it uses current-mode translinear circuits to perform computation in low power. Experimental results are presented, demonstrating its capabilities through an integration in a Lab-on-Chip (LoC) set-up using a microfluidic assembly.
Kalofonou M, 2013, Semiconductor technology for detection of DNA methylation based biomarkers in early screening of cancer
The role of DNA methylation based biomarkers in several stages of cancer development is a rapidly advancing area of research. The aberrancies on the methylation profile of gene promoters play a critical role in gene silencing, thus contributing in different phases of tumour initiation, progression and recurrence, also associated with predicting the response to chemotherapeutic agents, therefore leading to a better assessment of the clinical effectiveness of cancer therapies and so of better prognosis. The need for detection of DNA methylation has become one of the most important assays in early cancer screening. This work introduces the use of semiconductor technology for detection of DNA methylation based biomarkers in CMOS for early screening of cancer using the Ion-Sensitive Field-Effect Transistor (ISFET). This enables label-free detection of DNA methylation in gene markers of interest associated with tumour development in different organs, ultimately enabling a Point-of-Care (PoC) system for early cancer diagnosis. Towards this goal, we introduce the concept of ratiometric detection using the "Methylation Cell" which allows continuous computation of the DNA methylation ratio. This was demonstrated through a Lab-on-Chip (LoC) system using low power current-mode translinear circuits fabricated in unmodified CMOS. Complementary to this, a novel implementation of the "Gilbert Gain Cell" integrated with ISFET sensors was proposed, referred to as the ISFET based Chemical Gilbert Cell, a current-mode circuit for differential reaction monitoring of pH signals derived from DNA methylation reactions. The Cell achieves elimination of common non-idealities of ISFETs such as drift reduction and temperature variations, while achieving gain tunability.
Kalofonou M, Toumazou C, 2013, Semiconductor technology for early detection of DNA methylation for cancer: From concept to practice, SENSORS AND ACTUATORS B-CHEMICAL, Vol: 178, Pages: 572-580, ISSN: 0925-4005
The electrical detection of DNA methylation based biomarkers using semiconductor technology shows great promise for early cancer screening. Presented is the very first proof-of-concept example of using CMOS-based technology for real-time DNA methylation detection using Ion-Sensitive Field-Effect Transistors (ISFETs). An electrochemical label-free approach was applied in two gene assays, each one of which incorporated the sequences of DAPK1 and CDKN2A/p16-INK4 (p16) gene promoters at a both methylated and unmethylated state, performing isothermal methylation-specific amplification and detection both in-tube and on-chip (real-time). Good discrimination was shown between the two states, achieving a very good average pH signal change for the methylated state of 1.91 for DAPK1 assay and of 1.58 for p16 assay in the tube test. The real-time on-chip test showed similarly good real-time differential signal change in favour of methylated DNA, reaching 37 mV for DAPK1 assay and 23 mV for p16 assay, validating the results from the proof-of-concept test of pH-LAMP in-tube while confirming the sensitivity of real-time methylation-specific pH-LAMP on-chip.
Kalofonou M, Georgiou P, Ou C-P, et al., 2012, An ISFET based translinear sensor for DNA methylation detection, SENSORS AND ACTUATORS B-CHEMICAL, Vol: 161, Pages: 156-162
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- Citations: 28
Kalofonou M, Georgiou P, Toumazou C, 2011, An ISFET based chemical Gilbert Cell, IEEE Biomedical Circuits and Systems Conference (BioCAS) 2011, Publisher: IEEE, Pages: 365-368
This paper presents an ISFET based chemical Gilbert Cell capable of differential measurement of pH signals during thermocycling reactions. Such a process is important for DNA analysis during PCR, with the capability to be applied in Lab-On-Chip (LOC) topologies. The proposed circuit is capable of measuring the difference between two reaction chambers allowing stable drift reduction. The system has been designed and fabricated in a typical 0.35μm CMOS process, with the resulting topology achieving differential measurement, tunable gain of up to 40dB, temperature stability, with a variation of just 0.7% within the range of 0 to 100°C and a low power consumption of 198nW. © 2011 IEEE.
Kalofonou M, Toumazou C, 2011, ISFET based chemical Gilbert cell, Electronics Letters, Vol: 47, Pages: 903-904, ISSN: 0013-5194
Antonacopoulou A, Floratou K, Stavropoulos M, et al., 2008, The polymorphism-31G/C of survivin influences the expression levels of isoforms survivin-2B, -delta Ex3 and -2 alpha in neoplastic colonic tissue, Publisher: Wiley: FEBS Journal, Pages: 135-135, ISSN: 1742-4658
Introduction: Survivin belongs to the family of the inhibitors of apoptosis and has a role in cell division and proliferation. There are at least five isoforms of survivin which seem to have opposing roles regarding apoptosis and may be necessary for the regulation of the action of survivin. In the present study, the relationship between the expression of four of the isoforms of survivin and the promoter polymorphism -31G/C was assessed in colon cancer.Methods: Blood and colonic tissue (neoplastic and normal) was obtained from 46 patients with primary colon cancer. Survivin, survivin-2B, survivin-dEx3 and survivin-2a mRNA levels in tissue samples were assessed with quantitative RT-PCR. The promoter polymorphism -31G/C was detected in DNA from the blood samples with real time PCR.Results: All isoforms were expressed in higher levels in neoplastic tissue compared to normal (P < 0.001). Regarding the -31G/C polymorphism, 52.2% (24/46) of the patients were heterozygotes and 43.4% (20/46) homozygotes GG, while CC were only 4.4% (2/46). In neoplastic tissues, the presence of the C allele correlated with higher levels of expression of the isoforms studied (not statistically significant for survivin) although there was no difference in the levels in the normal tissue.Conclusions: All isoforms are overexpressed in neoplastic tissue. The G allele was more frequently detected than the C and it correlates with lower expression levels of survivin-2B, -dEx3 and -2a in neoplastic tissue.
Antonacopoulou A, Floratou K, Stavropoulos M, et al., 2008, The polymorphism-31G/C of survivin influences the expression levels of isoforms survivin-2B, -delta Ex3 and -2 alpha in neoplastic colonic tissue, Pages: 135-135, ISSN: 1742-4658
Introduction: Survivin belongs to the family of the inhibitors of apoptosis and has a role in cell division and proliferation. There are at least five isoforms of survivin which seem to have opposing roles regarding apoptosis and may be necessary for the regulation of the action of survivin. In the present study, the relationship between the expression of four of the isoforms of survivin and the promoter polymorphism -31G/C was assessed in colon cancer. Methods: Blood and colonic tissue (neoplastic and normal) was obtained from 46 patients with primary colon cancer. Survivin, survivin-2B, survivin-dEx3 and survivin-2a mRNA levels in tissue samples were assessed with quantitative RT-PCR. The promoter polymorphism -31G/C was detected in DNA from the blood samples with real time PCR. Results: All isoforms were expressed in higher levels in neoplastic tissue compared to normal (P < 0.001). Regarding the -31G/C polymorphism, 52.2% (24/46) of the patients were heterozygotes and 43.4% (20/46) homozygotes GG, while CC were only 4.4% (2/46). In neoplastic tissues, the presence of the C allele correlated with higher levels of expression of the isoforms studied (not statistically significant for survivin) although there was no difference in the levels in the normal tissue. Conclusions: All isoforms are overexpressed in neoplastic tissue. The G allele was more frequently detected than the C and it correlates with lower expression levels of survivin-2B, -dEx3 and -2a in neoplastic tissue.
Antonacopoulou A, Floratou K, Stavropoulos M, et al., 2008, The polymorphism-31G/C of survivin influences the expression levels of isoforms survivin-2B, -delta Ex3 and -2 alpha in neoplastic colonic tissue, FEBS Journal, Pages: 135-135, ISSN: 1742-464X
Introduction: Survivin belongs to the family of the inhibitors of apoptosis and has a role in cell division and proliferation. There are at least five isoforms of survivin which seem to have opposing roles regarding apoptosis and may be necessary for the regulation of the action of survivin. In the present study, the relationship between the expression of four of the isoforms of survivin and the promoter polymorphism -31G/C was assessed in colon cancer. Methods: Blood and colonic tissue (neoplastic and normal) was obtained from 46 patients with primary colon cancer. Survivin, survivin-2B, survivin-dEx3 and survivin-2a mRNA levels in tissue samples were assessed with quantitative RT-PCR. The promoter polymorphism -31G/C was detected in DNA from the blood samples with real time PCR. Results: All isoforms were expressed in higher levels in neoplastic tissue compared to normal (P < 0.001). Regarding the -31G/C polymorphism, 52.2% (24/46) of the patients were heterozygotes and 43.4% (20/46) homozygotes GG, while CC were only 4.4% (2/46). In neoplastic tissues, the presence of the C allele correlated with higher levels of expression of the isoforms studied (not statistically significant for survivin) although there was no difference in the levels in the normal tissue. Conclusions: All isoforms are overexpressed in neoplastic tissue. The G allele was more frequently detected than the C and it correlates with lower expression levels of survivin-2B, -dEx3 and -2a in neoplastic tissue.
Antonacopoulou A, Grivas P, Skarlas L, et al., 2008, POLR2F, ATP6V0A1 and PRNP Expression in Colorectal Cancer: New Molecules with Prognostic Significance?, Anticancer Research, Vol: 28, Pages: 1221-1227, ISSN: 1791-7530
Background: DNA-directed RNA polymerase II subunit F (POLR2F), a subunit of the V0 domain of the vacuolar ATPase (ATP6V0A1) and the prion protein (PRNP) are molecules of potential importance in carcinogenesis and targeted cancer therapy. However, their expression has not been studied in colorectal carcinomas. Patients and Methods: Expression microarray data were analyzed using a novel computational tool to reveal elevated levels of POLR2F, ATP6V0A1 and PRNP in relapsed colorectal carcinoma patients. The mRNA levels of POLR2F, ATP6V0A1 and PRNP were evaluated by quantitative RT-PCR in 70 colorectal carcinomas and 17 normal tissue specimens and were correlated with clinicopathological parameters. Results: POLR2F and PRNP were up-regulated in colorectal carcinomas. Moreover, a significant difference in the expression levels of all three molecules between the right colon and the rectum was observed. High expression levels of POLR2F and ATP6V0A1 correlated with improved 3-year survival. Moreover, PRNP expression constituted an independent prognostic factor of the 3-year survival in multivariate analysis. Conclusion: POLR2F and PRNP exhibited elevated levels in carcinomas compared to normal tissue samples suggesting a possible role for these molecules in colorectal cancer. The association of the three molecules with survival or disease prognosis warrants further investigation.
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