Cancer Biomarkers - Volume 10, issue 1

Article Type: Editorial

DOI: 10.3233/CBM-2012-0241

Citation: Cancer Biomarkers, vol. 10, no. 1, pp. 1-2, 2012

Authors: Nolen, Brian M. | Langmead, Christopher J. | Choi, Sunguk | Lomakin, Aleksey | Marrangoni, Adele | Bigbee, William L. | Weissfeld, Joel L. | Wilson, David O. | Dacic, Sanja | Siegfried, Jill M. | Lokshin, Anna E.

Article Type: Research Article

Abstract: Background: Computed tomography (CT) scanning has emerged as an effective means of early detection for lung cancer. Despite marked improvement over earlier methodologies, the low level of specificity demonstrated by CT scanning has limited its clinical implementation as a screening tool. A minimally-invasive biomarker-based test that could further characterize CT-positive patients based on risk of malignancy would greatly enhance its clinical efficacy. Methods: We performed an analysis of 81 serum proteins in 92 patients diagnosed with lung cancer and 172 CT-screened control individuals. We utilize a series of bioinformatics algorithms including Metropolis-Monte Carlo, artificial neural networks, NaÃŕve Bayes, …and additive logistic regression to identify multimarker panels capable of discriminating cases from controls with high levels of sensitivity and specificity in distinct training and independent validation sets. Results: A three-biomarker panel comprised of MIF, prolactin, and thrombospondin identified using the Metropolis-Monte Carlo algorithm provided the best classification with a %Sensitivity/Specificity/Accuracy of 74/90/86 in the training set and 70/93/82 in the validation set. This panel was effective in the classification of control individuals demonstrating suspicious pulmonary nodules and stage I lung cancer patients. Conclusions: The selected serum biomarker panel demonstrated a high diagnostic utility in the current study and performance characteristics which compare favorably with previous reports. Further advancements may lead to the development of a diagnostic tool useful as an adjunct to CT-scanning. Show more

Keywords: Lung cancer, NSCLC, diagnosis, serum biomarkers, CT-scanning

DOI: 10.3233/CBM-2012-0229

Citation: Cancer Biomarkers, vol. 10, no. 1, pp. 3-12, 2012

Authors: Sebova, Katarina | Zmetakova, Iveta | Bella, Vladimir | Kajo, Karol | Stankovicova, Iveta | Kajabova, Viera | Krivulcik, Tomas | Lasabova, Zora | Tomka, Miroslav | Galbavy, Stefan | Fridrichova, Ivana

Article Type: Research Article

Abstract: Breast cancer is the most common cancer in women worldwide, representing 28.2% of all female malignancies. In addition to genetic changes, epigenetic events, as aberrant DNA methylation and histone modification, are responsible for cancer development. Many tumour suppressor genes are inactivated by DNA hypermethylation, which could be utilized for identification of new epigenetic biomarkers. To investigate the relation between DNA methylation level and breast cancer progression, we analysed DNA methylation in RASSF1A and CDH1 promoters using quantitative multiplex methylation-specific PCR in paraffin-embedded tumour tissues and blood samples from 92 breast cancer patients and 50 controls, respectively. The associations between RASSF1A …and CDH1 methylation levels and clinico-pathological parameters were tested by Kruskal-Wallis and van der Waerden ANOVA tests. Out of 92 breast cancer patients, 76 (82.6%) manifested various levels of RASSF1A (range from 1.20 to 92.63%) and 20 (21.7%) of CDH1 (range from 1.20 to 79.62%) methylation. However, no methylation was found in 50 controls. Increasing trends in RASSF1A methylation were observed in tumour size, lymph node status and TNM stage, but only CDH1 methylation levels showed statistically significant differences between the patient subgroups in lymph node status and IHC subtype. Overall, stable relatively high RASSF1A methylation could be utilised as universal tumour marker and the less frequent but highly methylated CDH1 promoter can serve for identification of potentially metastasising tumours. Show more

Keywords: Breast cancer, DNA hypermethylation, quantitative assay, RASSF1A methylation, CDH1 methylation, epigenetic biomarkers

DOI: 10.3233/CBM-2012-0230

Citation: Cancer Biomarkers, vol. 10, no. 1, pp. 13-26, 2012

Authors: Topilow, Arthur A. | Davis, John M. | Vernick, Jerome J. | Tang, Dengda | Corbett, Siobhan | Veltman, Thomas | Wagner, Sasha J. | Gilvarg, Charles

Article Type: Research Article

Abstract: Introduction: Pancreatic cancer has a dismal prognosis because it is often diagnosed at an advanced stage. Therefore, serological biomarkers are eagerly sought for early detection. The digestive enzyme pro-carboxypeptidase A (PCPA) may be able to fill this role. The purpose of this study was to validate and extend previous research done at New York University (NYU), demonstrating that measurement of serum PCPA is a sensitive biomarker for early stage pancreatic cancer. Materials and methods: Samples were collected from 10 early and 16 late stage patients at Jersey Shore University Medical Center (JSUMC) and Robert Wood Johnson Hospital (RWJ) …with adenocarcinoma of the head of the pancreas. Results: The percentages of early and late stage cancer patients with PCPA values above the upper limit (2.35u/L) were 90.0% and 56.0%, respectively. Mean PCPA values for early and late stage cancer were determined to be 22.95u/L and 3.55u/L, respectively. In one case, the prospective patient was detected by our assay one month before diagnosis. Additionally, data from an ampullary cancer patient supports the proposed mechanism behind this test. Conclusions: Combining the JSUMC and NYU results show 94% sensitivity, demonstrating that determining serum PCPA has the requisite sensitivity to detect early stage pancreatic cancer. Show more

Keywords: Early detection, pancreatic cancer, sensitivity, procarboxypeptidase, carboxypeptidase

DOI: 10.3233/CBM-2012-0225

Citation: Cancer Biomarkers, vol. 10, no. 1, pp. 27-33, 2012

Authors: Folio, Cecilia | Zalacain, Marta | Zandueta, Carolina | Ormazábal, Cristina | Sierrasesúmaga, Luis | Julián, Mikel San | de las Rivas, Javier | Toledo, Gemma | Lecanda, Fernando | Patiño-García, Ana

Article Type: Research Article

Abstract: Background: The cortactin (CTTN) gene has been found, by transcriptomic profiling, to be overexpressed in pediatric osteosarcoma. The location of CTTN at 11q13 and the role of cortactin in cytoskeleton restructuring make CTTN of interest as a potential biomarker for osteosarcoma. Materials and methods: Osteoblasts were isolated from 20 high-grade osteosarcomas before chemotherapy, and paired with cell samples from normal tissue, prior to RNA expression analysis on HG-U133A chips (Affymetrix). Semiquantitative CTTN mRNA expression was analyzed by real-time PCR. An osteosarcoma tissue microarray (TMA) containing 233 tissue spots from 48 patients was used for an immunohistochemical (IHC) study …of cortactin. Results: Transcriptomic profiling and real-time PCR analysis indicated increased CTTN expression in osteosarcomas (p=0.001, Student’s T test). TMA IHC showed cortactin to be present more frequently and in greater abundance in osteosarcomas than non-tumoral osteoblastic samples (p< 0.006, Mann-Withney test). Analysis of clinical outcomes indicated that overall survival for patients with primary tumors positive for cortactin was significantly lower than that for patients with cortactin negative (or only weakly staining) tumors (p=0.0278, Log-rank test). Conclusions: Our preliminary data support the hypothesis that over-expression of cortactin, contained in the 11q13 amplicon, is involved in osteosarcoma carcinogenesis. The potential of cortactin overexpression as a biomarker for osteosarcoma is consolidated. Show more

Keywords: Cortactin, expression analysis, metastasis, osteosarcoma, survival

DOI: 10.3233/CBM-2012-0227

Citation: Cancer Biomarkers, vol. 10, no. 1, pp. 35-41, 2012

Authors: Sawhney, Hemant | Kumar, C. Anand

Article Type: Research Article

Abstract: Background: Oral cancer is currently the most frequent cause of cancer-related deaths, which is usually preceded by oral pre-cancerous lesions and conditions. Altered glycosylation of glycoconjugates, such as sialic acid, fucose, etc. are amongst the important molecular changes that accompany malignant transformation. The purpose of our study was to evaluate usefulness of serum Total Sialic Acid (TSA) and serum Lipid-Bound Sialic Acid (LSA) as markers of oral precancerous lesions and histopathologically correlating them with grades of epithelial dysplasia. Methods: Blood samples were collected from 50 patients with oral precancer (Leukoplakia & OSMF), 25 patients with untreated oral cancer …and 25 healthy subjects. Serum sialic acid (total and lipid bound) levels were measured spectrophotometrically. Tissue samples from all the patients were evaluated for dysplasia. Results: Serum levels of total and lipid bound sialic acid were significantly elevated in patients with oral precancer and cancer when compared with healthy subjects. Analysis of variance test documented that there is progressive rise in serum levels of sialic acid with the degree of dysplastic changes in oral precancer patients. We observed positive correlation between serum levels of the markers and the extent of malignant disease (TNM Clinical staging) as well as histopathological grades. Conclusion: The results suggested that serum levels of TSA and LSA progressively increases with grades of dysplasia in precancerous groups and cancer group, when compared with healthy controls. These glycoconjugates, especially LSA has the clinical utility in indicating a premalignant change. Show more

Keywords: Dysplasia, glycoproteins, oral cancer, oral precancerous lesion, oral precancerous condition, sialic acid

DOI: 10.3233/CBM-2012-0226

Citation: Cancer Biomarkers, vol. 10, no. 1, pp. 43-49, 2012

Authors: Bravo-Calderón, Diego Mauricio | Oliveira, Denise Tostes | Marana, Aparecido Nilceu | Nonogaki, Suely | Carvalho, André Lopes | Kowalski, Luiz Paulo

Article Type: Research Article

Abstract: The aim of this study was to evaluate the expression of β2-adrenergic receptor (β2-AR) in oral squamous cell carcinoma (OSCC) and to investigate the correlations between expression level and clinical characteristics, outcome, and patient prognosis. A total of 106 OSCC patients underwent surgical treatment at the A.C. Camargo Cancer Hospital, São Paulo, Brazil, were analyzed for clinicopathological data, treatment, tumor outcome, prognosis and immunohistochemical expression of β2-AR. The β2-AR expression was statistically analyzed relative to clinicopathological variables and survival using the Chi-square test, Kaplan-Meier curves and Cox regression model. Most OSCC (72.6%) exhibited malignant cells with strong cytoplasmatic and membranous …β2-AR expression. β2-AR expression was significantly associated with alcohol (p=0.021), simultaneous consumption of alcohol and tobacco (p=0.014) and T stage (p=0.07). In addition, OSCC patients who exhibited strong β2-AR expression demonstrated a higher rate of overall survival (p=0.001) and cancer specific survival (p=0.004) compared to patients with weak/negative β2-AR expression. The Cox regression model demonstrated that strong β2-AR expression was an independent favorable prognostic factor for OSCC patients. These results suggest that the strong malignant cell β2-AR expression is a favorable prognostic factor for OSCC patients and could be used as a target for new anti-neoplastic pharmacological strategies. Show more

Keywords: Oral cancer, adrenergic receptor, stress

DOI: 10.3233/CBM-2012-0228

Citation: Cancer Biomarkers, vol. 10, no. 1, pp. 51-59, 2012