Cancer Biomarkers - Volume 3, issue 2

Authors: Govindan, S. | Ahmad, S.N. | Vedicherla, B. | Kodati, V. | Jahan, P. | Rao, K.P. | Ahuja, Y.R. | Hasan, Q.

Article Type: Research Article

Abstract: Endometriosis, uterine fibroids and breast cancer are female health disorders associated with a great deal of morbidity. Since all these disorders are hormone responsive, our present study has been carried out to identify the association of 306bp Alu insertion polymorphism in intron 7 of progesterone receptor gene (PROGINS). DNA was isolated from the blood samples of 445 Asian Indian women, which included 100 endometriosis, 80 fibroids and 157 cases of breast cancer along with 108 age matched normal healthy women as controls. PROGINS polymorphism was assessed by PCR followed by agarose gel electrophoresis. Results showed that T2 allele frequency is …5%, 10% and 14.6% in endometriosis, uterine fibroids and breast cancer, as compared to 5.5% in controls. This indicates that PROGINS can be considered as a predisposing risk marker for breast cancer but not for endometriosis and uterine fibroids. Show more

Keywords: Endometriosis, breast cancer, uterine fibroids, progesterone receptor, PROGINS

DOI: 10.3233/CBM-2007-3201

Citation: Cancer Biomarkers, vol. 3, no. 2, pp. 73-78, 2007

Authors: Volk, Michael L. | Hernandez, Jose C. | Su, Grace L. | Lok, Anna S. | Marrero, Jorge A.

Article Type: Research Article

Abstract: Current surveillance strategies for hepatocellular carcinoma (HCC) are applied uniformly in patients with cirrhosis, regardless of their cancer risk. The aim of this study was to compare the performance characteristics of the biomarkers alpha-fetoprotein (AFP), des-gamma carboxyprothrombin (DCP), and lectin-bound AFP (AFP-L3) in the diagnosis of HCC, and to determine the effect of risk factors for HCC on test performance. Eighty-four patients with HCC and 169 patients with cirrhosis were enrolled and their serum analyzed for total AFP, AFP-L3 and DCP. Receiver-operating characteristic (ROC) curves were constructed to determine the performance characteristics. DCP was significantly better than total AFP or …AFP-L3 in differentiating HCC from cirrhosis, with a sensitivity of 86% and specificity of 93%. When subjects were divided into two groups by their risk for HCC, all 3 markers had a lower sensitivity and area under the ROC curve in the high-risk group compared to the low-risk group. In conclusion, DCP has the best performance characteristics of all 3 serum markers for the diagnosis of HCC. Serum biomarkers may be less sensitive and specific in the highest risk patients. Show more

Keywords: Hepatocellular carcinoma, biomarkers, risk factors, alpha-fetoprotein, des-gamma-carboxyprothrombin, lectin-bound AFP

DOI: 10.3233/CBM-2007-3202

Citation: Cancer Biomarkers, vol. 3, no. 2, pp. 79-87, 2007

Authors: Martinez-Ferrandis, José I. | Rodríguez-López, Raquel | Milne, Roger L. | González, Emilio | Cebolla, Elvira | Chirivella, Isabel | Zamora, Pilar | Arias, José I. | Palacios, Santiago | Cervantes, Andrés | Díez, Orland | Benitez, Javier | Armengod, M.-Eugenia

Article Type: Research Article

Abstract: TRAIL is a potent inducer of apoptosis in malignant but not in normal cells. TRAIL binds to the proapoptotic death receptor DR4 and DR5 as well as to the decoy receptors DcR1 and DcR2. To evaluate the involvement of TRAIL receptor genes in breast cancer, we carried out a case-control study of eight selected polymorphisms in a large sample of Spanish women. Three of the eight selected SNPs (626G/C and 1322G/A in DR4 and 2699A/G in DcR2) showed some evidence of different genotype distributions in a random selection of 535 cases and 480 controls and were therefore studied in our …entire sample (1008 cases and 768 controls). For the two DR4 polymorphisms, no differences in genotype or haplotype distribution were found between cases and controls. Interestingly, allele 2699G in the decoy receptor DcR2 appears associated with reduced breast cancer risk (P=0.05). Given that it is located in the 3' UTR, its effect might be related to DcR2 mRNA instability, or linkage disequilibrium with a functional variant residing in either DcR2 or neighbouring genes. A decreased efficiency of DcR2 to work as decoy receptor for TRAIL, would facilitate the apoptotic pathway in cells at risk. Show more

Keywords: Breast cancer risk, trail receptors, apoptosis, polymorphisms

DOI: 10.3233/CBM-2007-3203

Citation: Cancer Biomarkers, vol. 3, no. 2, pp. 89-93, 2007

Authors: Phillips, Michael | Altorki, Nasser | Austin, John H.M. | Cameron, Robert B. | Cataneo, Renee N. | Greenberg, Joel | Kloss, Robert | Maxfield, Roger A. | Munawar, Muhammad I. | Pass, Harvey I. | Rashid, Asif | Rom, William N. | Schmitt, Peter

Article Type: Research Article

Abstract: Background: Normal metabolism generates several volatile organic compounds (VOCs) that are excreted in the breath (e.g. alkanes). In patients with lung cancer, induction of high-risk cytochrome p450 genotypes may accelerate catabolism of these VOCs, so that their altered abundance in breath may provide biomarkers of lung cancer. Methods: VOCs in 1.0 L alveolar breath were analyzed in 193 subjects with primary lung cancer and 211 controls with a negative chest CT. Subjects were randomly assigned to a training set or to a prediction set in a 2:1 split. A fuzzy logic model of breath biomarkers of lung cancer …was constructed in the training set and then tested in subjects in the prediction set by generating their typicality scores for lung cancer. Results: Mean typicality scores employing a 16 VOC model were significantly higher in lung cancer patients than in the control group (p<0.0001 in all TNM stages). The model predicted primary lung cancer with 84.6% sensitivity, 80.0% specificity, and 0.88 area under curve (AUC) of the receiver operating characteristic (ROC) curve. Predictive accuracy was similar in TNM stages 1 through 4, and was not affected by current or former tobacco smoking. The predictive model achieved near-maximal performance with six breath VOCs, and was progressively degraded by random classifiers. Predictions with fuzzy logic were consistently superior to multilinear analysis. If applied to a population with 2% prevalence of lung cancer, a screening breath test would have a negative predictive value of 0.985 and a positive predictive value of 0.163 (true positive rate =0.277, false positive rate =0.029). Conclusions: A two-minute breath test predicted lung cancer with accuracy comparable to screening CT of chest. The accuracy of the test was not affected by TNM stage of disease or tobacco smoking. Alterations in breath VOCs in lung cancer were consistent with a non-linear pathophysiologic process, such as an off-on switch controlling high-risk cytochrome p450 activity. Further research is needed to determine if detection of lung cancer with this test will reduce mortality. Show more

DOI: 10.3233/CBM-2007-3204

Citation: Cancer Biomarkers, vol. 3, no. 2, pp. 95-109, 2007

Authors: Rothhammer, Tanja | Wild, Peter J. | Meyer, Stefanie | Bataille, Frauke | Pauer, Armin | Klinkhammer-Schalke, Monika | Hein, Rüdiger | Hofstaedter, Ferdinand | Bosserhoff, Anja K.

Article Type: Research Article

Abstract: The purpose of this study was to investigate whether protein expression of bone morphogenetic protein 7 (BMP7) is associated with clinico-pathologic characteristics in benign and malignant melanocytic skin tumors. Tissue microarrays (TMAs) were used to analyze BMP7 expression and the Ki-67 labeling index immunohistochemically. Expression was scored semi quantitatively (0–2+). BMP7 protein expression of any intensity (1+–2+) was detected in 50.2% (153/305) of informative cases. In general, BMP7 expression was significantly induced in malignant melanomas (P< 0.001) and melanoma metastases (P< 0.001), compared to benign nevi. Additionally, expression of BMP7 in primary melanomas was associated with Ki-67 labeling index > …5% suggesting that induction of BMP7 expression is associated with proliferation (P=0.028). None of the other clinical and histological factors analyzed was significantly related to BMP7 expression. Interestingly, lymph node metastases demonstrated a significantly higher BMP7 expression compared to skin metastases (P<0.01). Strong BMP7 expression (score 2+) was significantly associated with shorter tumor recurrence (P< 0.05). In summary, induction of BMP7 expression is frequent in melanomas and may serve as a novel prognostic marker of progression in melanoma patients. Show more

Keywords: Malignant melanoma, skin neoplasms, immunohistochemistry, bone morphogenetic proteins, tissue array, prognosis

DOI: 10.3233/CBM-2007-3205

Citation: Cancer Biomarkers, vol. 3, no. 2, pp. 111-117, 2007