Cancer Biomarkers - Volume 11, issue 1

Authors: Baine, Michael J. | Menning, Melanie | Smith, Lynette M. | Mallya, Kavita | Kaur, Sukhwinder | Rachagani, Satyanarayana | Chakraborty, Subhankar | Sasson, Aaron R. | Brand, Randall E. | Batra, Surinder K.

Article Type: Research Article

Abstract: Background: We sought to validate global microarray results indicating the differential expression of 383 genes in Peripheral Blood Mononuclear Cells (PBMCs) from patients with pancreatic cancer (PC) and to further evaluate their PC diagnostic potential. Methods and materials: In total, 177 patients were recruited (47 healthy controls (HC), 35 chronic pancreatitis (CP) patients, and 95 PC patients). PBMC expressions of six genes from our previous study (ANXA3, ARG1, CA5B, F5, SSBP2, and TBC1D8) along with four new genes (MIC1, NGAL, MUC1, and MUC16) were analyzed using multiplex Q-RT PCR. Results: Differential expressions of 5 of the …6 genes previously identified by PBMC microarray were validated in this study. Multivariate models for PBMC gene expression were attempted to determine if any combination was diagnostically superior to CA19-9 alone. We found that addition of PBMC CA5B, F5, SSBP2, and MIC1 expression levels to CA19-9 significantly improved CA19-9’s diagnostic abilities when comparing resectable PC to CP patients (p=0.023). Conclusions: Results of our previous study were validated, indicating reproducibility of PC-associated PBMC expression profiling. We identified a score-based model that can differentiate resectable PC from CP better than CA19-9, potentiating that PBMC differential expression analysis may offer a novel tool for early PC diagnosis. Show more

Keywords: Pancreatic cancer, chronic pancreatitis, PBMC, CA19-9, diagnosis

DOI: 10.3233/CBM-2012-0260

Citation: Cancer Biomarkers, vol. 11, no. 1, pp. 1-14, 2012

Authors: Trojani, Alessandra | Di Camillo, Barbara | Tedeschi, Alessandra | Lodola, Milena | Montesano, Simona | Ricci, Francesca | Vismara, Eleonora | Greco, Antonino | Veronese, Silvio | Orlacchio, Aldo | Martino, Sabata | Colombo, Chiara | Mura, Mariangela | Nichelatti, Michele | Colosimo, Anna | Scarpati, Barbara | Montillo, Marco | Morra, Enrica

Article Type: Research Article

Abstract: Background: Several studies demonstrated IGVH mutational status and ZAP70 expression as the most relevant prognostic markers in Chronic Lymphocytic Leukemia (CLL), suggesting the separation of two patient subgroups: with good mutated ZAP70 negative (MTZAP70- ) and poor unmutated ZAP70 positive (UMZAP70+ ) prognosis. Design and methods: We determined the gene expression of B cells in 112 CLL patients divided into three classes: class 1 with MTZAP70- , class 2 with UMZAP70+ , and class 3 included both UMZAP70- and MTZAP70+ . Results: We found LPL, AGPAT2, MBOAT1, CHPT1, AGPAT4, PLD1 genes encoding enzymes involved in …lipid metabolism overexpressed in UMZAP70+ . In addition, this study identified ARSD, a gene belonging to the sphingolipid metabolism, as a new gene significantly overexpressed in UMZAP70+ compared to MTZAP70- . Western blots confirmed that ARSD protein levels were significantly different between the 3 classes of patients and normal controls. Statistical analysis identified a significant correlation between ARSD and IGVH; however, both ARSD protein level and IGVH were independently associated with the need for therapy of CLL patients. Conclusions: ARSD is a novel prognostic factor as the time to start therapy is shorter in patients with high levels of ARSD protein and sphingolipid metabolism could represent a new biological mechanism in CLL. Show more

Keywords: CLL, microarray, IGVH, ARSD

DOI: 10.3233/CBM-2012-0259

Citation: Cancer Biomarkers, vol. 11, no. 1, pp. 15-28, 2012

Authors: Wang, Wen | Zhao, Lan-Juan | Wang, Yan | Tao, Qing-Yuan | Feitelson, Mark A. | Zhao, Ping | Ren, Hao | Qi, Zhong-Tian

Article Type: Research Article

Abstract: Background: Hepatitis B virus (HBV) carriers are at high risk for the development of hepatocellular carcinoma (HCC), but there are no reliable markers that will identify such high-risk patients. HBV up-regulates the expression of selected genes (URGs) in the liver during chronic infection. These aberrantly expressed proteins trigger corresponding antibodies (anti-URGs) that appear prior to the detection of HCC. This study was undertaken to see if the anti-URGs could be used as early warning biomarker of HBV-induced liver cirrhosis and HCC. Methods: A cross sectional study using a total of 625 serum samples from HBV infected and uninfected …controls were tested for the anti-URGs using specific ELISAs. Results: The number and specificity of anti-URGs correlated with the severity of liver disease Anti-URGs were predominantly present among patients with HBV-associated HCC (55.2%) and cirrhosis (60.7%), and at a lower frequency among patients with chronic hepatitis (35.8%), and at still lower frequencies in most asymptomatic carriers (12.3%) with normal ALT, among patients with chronic hepatitis C (38.5%) and blood donors (0.9%). These anti-URGs were rarely detected in sera from those with tumors other than HCC, except among HBV infected patients with cholangioicarcinoma and in some patients with drug induced hepatitis. 3 or more anti-URGs could precede the diagnosis of cirrhosis or HCC 11.8 months on average, and HBV hepatitis patients with 3 or more anti-URGs have much higher risk (5/20 vs 0/30) to develop cirrhosis and HCC than those patients with less anti-URGs. As the early warning biomarker, 3 or more anti-URGs were served as the threshold to separate the cirrhosis and HCC from others with a moderate sensitivity (58.3%) and specificity (80.0%), which was better than other biomarkers (AFP, AFP-L3, GPC3 and GP73) and would improve up to 70.3% when combined with another biomarker. Conclusions: The results of this clinical validation study suggest that the anti-URGs might have diagnostic/prognostic utility among patients at high risk for the development of cirrhosis and HCC. Show more

Keywords: Anti-URGs, Hepatocellular carcinoma, hepatitis B virus x antigen, biomarker, early diagnosis

DOI: 10.3233/CBM-2012-0261

Citation: Cancer Biomarkers, vol. 11, no. 1, pp. 29-39, 2012

Authors: Attia, Fadia M. | Hassan, Amany M. | El-Maraghy, Nermine N. | Ibrahium, Gehan H.

Article Type: Research Article

Abstract: Introduction: To date, little is known about blood immune marker changes that may be related to the development of Non Hodgkin Lymphoma (NHL) and treatment response with few serum biomarkers that could be useful in follow- up of the patients. Objective: To quantify the expression of suppressor of cytokine signalling-3-(SOCS-3) gene at the mRNA level in the peripheral blood of patients with NHL and correlate with clinical pathological features and response to treatment. Methods: Thirty patients with NHL and 20 healthy controls were enrolled in the study. The SOCS-3 mRNA level in peripheral blood (PB) was …detected by semi-quantitative real-time polymerase chain reaction. Quantification of cytokines such as interleukin 6 and tumour necrosis factor alpha (IL-6 & TNF-α ) were performed using sandwich enzyme-linked immunosorbent assays (ELISA). Results: Increased expression of SOCS-3 mRNA in peripheral blood plus increased serum levels of IL-6 and TNF alpha from NHL cases with no complete remission after therapy. Higher levels of expression of SOCS-3 are associated with advanced disease, bone marrow involvement, extranodal involvement, poor performance status, B cell symptoms (fever, night sweats and weight loss) and high serum lactate dehydrogenase level which are evaluated by international prognostic index (IPI). Complete responses occur in 60% of patients with normal expression of SOCS-3 gene. Increased expression of SOCS-3 is common in diffuse large B cell lymphoma, CLL/small lymphocytic B cell lymphoma and follicular lymphoma. Conclusions: Over-expression of SOCS-3 mRNA from peripheral blood of NHL patients correlates with advanced disease and poor response to treatment. SOCS-3 mRNA expression in peripheral blood from NHL patients might be used to monitor response during treatment. Show more

Keywords: Suppressor of cytokine signalling-3 mRNA expression, IL-6, TNF-α and Non-Hodgkin's Lymphoma

DOI: 10.3233/CBM-2012-0262

Citation: Cancer Biomarkers, vol. 11, no. 1, pp. 41-47, 2012

Authors: Mareĉko, Ilona | Cvejić, Dubravka | Tatić, Svetislav | Dragutinović, Vesna | Paunović, Ivan | Savin, Svetlana

Article Type: Research Article

Abstract: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have roles in physiological and pathological processes. We evaluated immunohistochemical expression of MMP-2 and TIMP-2 in paraffin sections of 12 human fetal thyroids at mid-term gestation and 79 thyroid tumors of follicular origin. Besides evaluating expression of these proteins during fetal development and neoplastic transformation, we determined whether expression of MMP-2 and TIMP-2 may help to differentiate papillary thyroid carcinoma (PTC) from follicular thyroid adenoma (FTA) and/or peritumoral tissue (PT). We also investigated their relationship with prognostically important clinicopathological parameters of PTC. Immunoreactive MMP-2 and TIMP-2 were found in all fetal thyroid …tissues examined. Tumor tissues contained variable amounts of MMP-2 and TIMP-2, with overexpression of these proteins in PTC compared to FTA and PT tissue. According to the statistical analysis, MMP-2 distinguished follicular variant of PTC from FTA and overall PTC from total nonmalignant lesions. In PTC, high MMP-2 expression correlated with lymph node metastasis (P=0.022), while high TIMP-2 expression was positively correlated with tumor size (P=0.049) and extrathyroid invasion (P=0.017). Overall, these results indicate a role for MMP-2 and TIMP-2 in both thyroid development and malignant transformation and suggest that positive immunohistochemistry for MMP-2 and TIMP-2 might support diagnosis of PTC and predict unfavorable biological behavior. Show more

Keywords: Human fetal thyroid, papillary thyroid carcinoma, matrix metalloproteinase-2, tissue inhibitors of matrix metalloproteinase-2, immunohistochemistry, clinico-pathological parameters

DOI: 10.3233/CBM-2012-0258

Citation: Cancer Biomarkers, vol. 11, no. 1, pp. 49-58, 2012