Cancer Biomarkers - Volume 1, issue 6

Authors: Zeh, H.J. | Winikoff, S. | Landsittel, D.P. | Gorelik, E. | Marrangoni, A.M. | Velikokhatnaya, L. | Winans, M.T. | Lee, K. | Moser, A. | Bartlett, D. | Lotze, M.T. | Siegfried, J.M. | Whitcomb, D. | Slivka, A. | Bigbee, W.L. | Lokshin, A.E.

Article Type: Research Article

Abstract: Early detection of pancreatic cancer might improve clinical outcome. Significant alterations in the levels of individual serum cytokines have been reported in pancreatic cancer. We hypothesized that a multicytokine panel could serve as biomarkers for pancreatic cancer. To evaluate the diagnostic utility of such a panel, we have utilized a novel multianalyte LabMAP™ profiling technology that allows simultaneous measurement of multiple markers. In this study, a panel of 31 serological markers including cytokines, chemokines, growth and angiogenic factors in combination with CA 19-9 was analyzed in sera of pancreatic cancer patients, patients with chronic pancreatitis, and matched control healthy subjects. …Statistical analysis identified a multicytokine panel that was able to distinguish pancreatic cancer from healthy controls with a sensitivity of 85.7% and specificity of 92.3%, which was superior to performance of CA 19-9 alone. Importantly, a multicytokine panel allowed the discrimination of pancreatic cancer from chronic pancreatitis with high sensitivity of 98% and specificity of 96.4%. In conclusion, we demonstrated that analysis of multiple serum cytokines using a novel LabMAP™ technology is a promising approach for development of a diagnostic assay for pancreatic cancer. Show more

Keywords: Pancreatic cancer, chronic pancreatitis, detection, multiplexed, LabMAP™, cytokines

DOI: 10.3233/CBM-2005-1601

Citation: Cancer Biomarkers, vol. 1, no. 6, pp. 259-269, 2005

Authors: Krishna, Smriti M. | Kattoor, Jayashree | Balaram, Prabha

Article Type: Research Article

Abstract: Nasopharyngeal carcinoma (NPC) is a unique tumour due to its aetiology, incidence pattern and its consistent association with Epstein-Barr virus (EBV). EBV encodes many viral proteins, which targets crucial cell cycle regulatory proteins. Cadherins are a family of transmembrane glycoproteins, which mediates Ca2+ -dependent intercellular adhesion. Epithelial (E)-cadherin is an important member of this family, which is expressed predominantly on the surface of epithelial cells. E-cadherin acts as an invasion/metastasis-suppressor gene, hence knowledge of the molecular mechanism that controls its expression or function is of primary importance in understanding the process of tumor invasion. Loss of E-cadherin function has been …shown to potentiate tumor cell invasion and interestingly, a large number of invasive tumors do not involve mutation of E-cadherin, but rather down regulation of expression. Hence in this study, an attempt was made to evaluate the protein level expression pattern of E-cadherin in relation to viral involvement and to correlate it with other clinico-pathological parameters. We observed a significant down regulation of E-cadherin in NPC and its histological subsets, when compared to the controls (p ‹ 0.001). Expression of E-cadherin ranged from mild to moderate and none of the NPC showed intense expression. E-cadherin expression showed a significant down-regulation in NPC lesions with EBV infection (r=−0.436, p ‹ 0.001). The down regulation of E-cadherin observed in NPC is in line with the previous reports in E-cadherin expression in various cancers. The total lack of E-cadherin expression in neoplastic cells might be due to hypermethylation of E-cadherin promoter or its down regulation by cellular transcription repressor. Our study also shows a significant down regulation of E-cadherin in the presence of EBV, which also might involve the cellular DNA methylation machinery. Show more

Keywords: Nasopharyngeal cancer, E-cadherin, EBV, immunohistochemistry, PCR

DOI: 10.3233/CBM-2005-1602

Citation: Cancer Biomarkers, vol. 1, no. 6, pp. 271-277, 2005

Authors: Deng, Bin | Ye, Nengsheng | Luo, Guoan | Chen, Xian | Wang, Yiming

Article Type: Research Article

Abstract: There is a growing interest in applying proteomics to gain insight into the mechanism of tumorigenesis, develop new markers for molecular diagnosis and accelerate drug development. In an attempt to find new stage-specific tumor markers, patients suffering from squamous cell lung carcinomas (SQCLC) at different pathologic stages have been selected to achieve differential protein expression patterns. Two-dimensional polyacrylamide gel electrophoresis (2-DE) profiles of human SQCLC and normal tissue were compared. Differential protein spots were identified with peptide mass fingerprinting (PMF) based on matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and database searching. A total of 63 unique proteins …were identified in this experiment. Among them, peroxiredoxin 1 (PRDX1) expression level was significantly increased from stage I to III, and had a slight decrease at stage IV; whereas, a lasting decrease in the expression level of tropomyosins 3 (TPM3), was observed with the malignant progression from I stage to IV stage. These results provide further insight into malignant transformation in SQCLC and proteins may serve as new biomarkers for early diagnosis. Show more

Keywords: Lung cancer, proteomics, stage-specific protein, human squamous cell lung carcinomas

DOI: 10.3233/CBM-2005-1603

Citation: Cancer Biomarkers, vol. 1, no. 6, pp. 279-286, 2005

Authors: Mittal, Rama Devi | Srivastava, Daya Shankar Lal | Mishra, Dhruva. K.

Article Type: Research Article

Abstract: Urokinase gene is believed to play a key role in tissue degradation and cell migration under various normal and pathological conditions, including cancer invasion and metastasis. It may be responsible in the development of prostate cancer (CaP), although there is lack of genetic evidence. Our aim was to study single nucleotide polymorphism (C/T) in 3'-untranslated region to investigate the possibility. DNA was extracted from blood samples of 103 CaP patients and 107 normal controls. Polymerase chain reaction (PCR) based restriction analysis was used to identify the C/T polymorphism of the urokinase gene. Significant difference in the frequency distribution of CT …and TT genotypes in CaP patients as compared to normal was observed (p=0.04). Two folds risk for prostate cancer with T alleles in north Indian population was apparent. We also observed significant association for TT genotypes with higher Gleason score of tumors in CaP patients (p<0.05). A positive association was also evident in tobacco users having T alleles with risk of CaP. Our findings demonstrated a positive association of T allele of 3'UTR of urokinase gene with the risk of prostate cancer. We therefore hypothesize that C/T polymorphism may influence the etiology of CaP and is likely to become another new marker. Show more

Keywords: Urokinase, polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), prostate cancer (CaP)

DOI: 10.3233/CBM-2005-1604

Citation: Cancer Biomarkers, vol. 1, no. 6, pp. 287-292, 2005