Cancer Biomarkers - Volume 7, issue 3

Authors: Partida-Pérez, Miriam | de la Luz Ayala-Madrigal, María | Peregrina-Sandoval, Jorge | Macías-Gómez, Nelly | Moreno-Ortiz, José | Leal-Ugarte, Evelia | Cárdenas-Meza, Mario | Centeno-Flores, Manuel | Maciel-Gutiérrez, Víctor | Cabrales, Enrique | Cervantes-Ortiz, Sergio | Gutiérrez-Angulo, Melva

Article Type: Research Article

Abstract: Leptin and adiponectin are cytokines produced by adipose tissue with opposite effects on tumor growth: the former stimulate whereas the latter inhibit it. The objective was to analyze the association of LEP A19G and ADIPOQ+45 T/G and +276 G/T polymorphisms in Mexican patients with colorectal cancer (CRC). 68 unrelated patients with CRC (study group) and 102 blood donors (control group); all subjects were Mestizos from western Mexico. The polymorphisms were established by PCR-RFLP on DNA samples obtained from peripheral blood. The LEP A19G polymorphism showed significant differences between CRC patients and control group (p= 0.01 for G/A genotype and p= …0.02 for the recessive model G/G +G/A); yet, in the analysis stratified by gender, this difference remained significant only in males. The ADIPOQ polymorphisms did not shown any significant differences. Our results suggest that the A19G LEP polymorphism is associated with CRC in Mexican patients. Show more

Keywords: Leptin, adiponectin, colorectal cancer, polymorphism

DOI: 10.3233/CBM-2010-0154

Citation: Cancer Biomarkers, vol. 7, no. 3, pp. 117-121, 2010

Authors: Shimwell, Neil J. | Wei, Wenbin | Wilson, Sue | Wakelam, Michael J. O. | Ismail, Tariq | Iqbal, Tariq | Johnson, Philip J. | Martin, Ashley | Ward, Douglas G.

Article Type: Research Article

Abstract: Background: Patients with colorectal cancer often present with advanced disease and concomitant poor prognosis. The best known serum biomarker, carcinoembryonic antigen (CEA) is not recommended for screening because of its limited specificity and sensitivity. A number of other circulating proteins have been suggested to be diagnostically useful but individually none of these has proved to be of sufficient sensitivity or specificity to establish a role in routine clinical practice. Here, we test the hypothesis that combining several of these biomarkers will improve diagnostic efficacy. Methods: To select the markers for our model we screened CEA and 26 other …candidate biomarkers. Four candidates were selected and their concentrations determined in the serum of 239 patients (106 colorectal cancer patients and 133 non-cancer subjects). Results: Class prediction models based on CEA, DR-70 and sCD26 produced a modest increase in detection accuracy over CEA alone, particularly for early stage cancers. The sensitivity and specificity required for a clinically useful test was not reached. Conclusion: It is unlikely that a biomarker panel comprised of the currently available serum markers will generate a clinically useful diagnostic test for colorectal cancer. Our findings reiterate the urgent need to discover novel biomarkers for the detection of colorectal cancer. Show more

DOI: 10.3233/CBM-2010-0155

Citation: Cancer Biomarkers, vol. 7, no. 3, pp. 123-132, 2010

Authors: Halfon, Philippe | Benmoura, Dominique | Agostini, Aubert | Khiri, Hacène | Pénaranda, Guillaume | Martineau, Agnès | Blanc, Bernard

Article Type: Research Article

Abstract: Background: The detection of high-risk human papillomavirus (HPV) DNA provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). Objectives: The aim of this study was to combine DNA- and RNA-based assays in order to improve the detection of advanced disease (CIN2+). Methods: 107 ASCUS+ women were included in Marseilles (France) between March 2007 and June 2008. Up to five tests were carried out on a liquid PreservCyt sample: Hybrid Capture 2 (HCII) (Digene), Papillocheck (Greiner), Abbott RealTime HR HPV (RT HR HPV) (Abbott), Linear Array (Roche), and EasyQ …HPV (Biomérieux). Results: 36 (34%) women had CIN2+ histology; among them 6 (6%) had CIN3+ histology. For CIN2+ detection, all tests had comparable sensitivities except EasyQ HPV test: HCII 94%, Papillocheck and LA 92%, RT HR HPV 89%, and NucliSENS EasyQ HPV 75% (P not significant). On the other hand, EasyQ HPV had a higher specificity than the other assays (except RT HR HPV assay). Combining DNA-based and RNA-based assay would allow to reduce the need of colposcopies to be performed among patients HPV positive with DNA-based assay: 32% (7/22) colposcopies not needed in < 30 years old patients, and 29% (14/49) colposcopies not needed in ⩾ 30 years patients. Conclusions: All tests had comparable diagnostic values for CIN2+ detection, but DNA-based tests seemed to be more sensitive and RNA-based assay more specific. The combined use of DNA- and RNA-based assays considerably reduces the number of colposcopies to be performed, and provides better diagnostic accuracy for CIN2+ disease. Show more

Keywords: DNA-based assays, RNA-based assays, colposcopy, stepwise algorithm

DOI: 10.3233/CBM-2010-0156

Citation: Cancer Biomarkers, vol. 7, no. 3, pp. 133-139, 2010

Authors: Rohrberg, Kristoffer Staal | Skov, Birgit Guldhammer | Lassen, Ulrik | Christensen, Ib Jarle | Høyer-Hansen, Gunilla | Buysschaert, Ian | Pappot, Helle

Article Type: Research Article

Abstract: The epidermal growth factor receptor (EGFR) and angiogenesis are well established targets in anti-cancer therapy. Several targeted anti-cancer therapies are in clinical trials in pancreatic and gastroesophageal (GEJ) cancer. However, many patients do not respond to these targeted therapies and there is therefore an increasing need for biomarkers for selection of patients to these therapies. We investigated the expression of EGFR, vascular endothelial growth factor A (VEGF-A), and VEGF receptor 2 (VEGFR-2) in tumour tissue by immunohistochemistry, and soluble EGFR (sEGFR), soluble VEGFR-2 (sVEGFR-2), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), plasminogen activator inhibitor 1 (PAI-1), and different …forms of the urokinase plasminogen activator receptor (uPAR): uPAR (I), uPAR (I–III), and uPAR (I–III)+(II–III) in plasma by quantitative immunoassays in 14 patients with pancreatic and GEJ cancer. We found expression in tumour tissue and the plasma levels to be similar to those found in patients with other tumour types. No correlation was found between the blood levels of soluble receptors and the corresponding tumour tissue levels. We conclude that these markers are present in pancreatic and GEJ cancer patients, and could be investigated further as predictive biomarkers in such patients treated with EGFR or angiogenesis targeted therapies. Show more

Keywords: Angiogenesis, epidermal growth factor receptor, pancreatic cancer, gastroesophageal junction cancer

DOI: 10.3233/CBM-2010-0157

Citation: Cancer Biomarkers, vol. 7, no. 3, pp. 141-151, 2010

Authors: Sponring, Andreas | Filipiak, Wojciech | Ager, Clemens | Schubert, Jochen | Miekisch, Wolfram | Amann, Anton | Troppmair, Jakob

Article Type: Research Article

Abstract: Analysis of volatile organic compounds (VOCs) provides an elegant approach for cancer screening and disease monitoring, whose use is currently limited by a lack of validated cancer-derived metabolites, which may serve as biomarkers. The aim of the experiments presented here was to investigate the release and consumption of VOCs from the non small cell lung cancer cell line NCI-H1666, which was originally derived from a bronchoalveolar carcinoma. Following detachment by trypsinization suspended cells were incubated in a sealed fermenter for 21 hours. 200 ml of headspace from the cell culture were sampled, diluted with dry, highly purified air and …preconcentrated by adsorption on three different solid sorbents with increasing adsorption strength. VOC-analysis was performed by thermodesorption-gas chromatography mass spectrometry (TD-GC-MS). In contrast to our previous studies experiments with NCI-H1666 cells only confirmed the consumption of several aldehydes, n-butyl acetate and the ethers methyl tert-butyl ether and ethyl tert-butyl ether, but no unequivocal release of VOCs was observed. Together with our previously published work these data indicate that the consumption of certain VOCs is commonly observed while their release shows cell line-restricted patterns, whose underlying causes are unknown. Show more

Keywords: Lung cancer, NCI-H1666 cells, volatile organic compounds (VOCs), thermodesorption, gas chromatography mass spectrometry

DOI: 10.3233/CBM-2010-0182

Citation: Cancer Biomarkers, vol. 7, no. 3, pp. 153-161, 2010

Authors: Selmy, Mohamed A. | Ibrahim, Gehan H. | El Serafi, Taher I. | Ghobeish, Ammar A.

Article Type: Research Article

Abstract: Background/Aim: Proepithelin is a growth factor that may play a critical role in bladder cancer. Its over-expression in urine of bladder cancer patients gave us the impetus to evaluate its potential suitability as a biomarker for bladder cancer diagnosis and/or prognosis. Methods: proepithelin was estimated in 86 voided urine samples, including 59 bladder cancer patients and 27 healthy volunteers using quantitative sandwich enzyme immunoassay technique. Urinary proepithelin level was expressed in ng/100 mg creatinine. Results: Urinary proepithelin was significantly higher in bladder cancer patients compared to control subjects (means: 17.5 ± 10 and 8.9 ± 3.5 …ng/100 mg creatinine, respectively; p < 0.001), and the test sensitivity and specificity to detect the presence of bladder cancer were 74.6 and 85.2%, respectively. Furthermore, patients with low-grade/non-muscle invasive stages bladder cancer showed significantly lower urinary proepithelin compared to high-grade/non-muscle invasive stages and high-grade/invasive stages ones (means: 11.6 ± 9, 20.2 ± 8.1 and 23.8 ± 11.9 ng/100 mg creatinine, respectively; p= 0.005 and 0.002, respectively). Conclusions: This preliminary study suggests that urinary proepithelin may be considered as a non-invasive, sensitive, and specific urine-based test for bladder cancer diagnosis and/or prognosis. Show more

Keywords: Proepithelin, bladder cancer, cancer detection, biomarker, invasion

DOI: 10.3233/CBM-2010-0186

Citation: Cancer Biomarkers, vol. 7, no. 3, pp. 163-170, 2010