Cancer Biomarkers - Volume 10, issue 6

Authors: Sy, Man-Sun | Altekruse, Sean F. | Li, Chaoyang | Lynch, Charles F. | Goodman, Marc T. | Hernandez, Brenda Y. | Zhou, Lan | Saber, Maria Sibug | Hewitt, Stephen M. | Xin, Wei

Article Type: Research Article

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is an important cause of cancer death with no clear prognostic biomarker. Expression of prion (PrP) has been reported to be a marker of poor prognosis in a series of Caucasian PDAC cases. We determined the prognostic value of PrP in a racially and geographically diverse population-based series of PDAC cases. PrP expression was examined in 142 PDAC cases from three cancer registries. Cases included 71 Caucasian, 54 Asian/Pacific Islanders and 17 Blacks diagnosed from 1983–2000, and followed through 2008. Hazard ratios (HR) and 95% confidence intervals (CIs) for the association of PrP expression with survival …were computed after adjustment for case attributes. The risk of death was about four times higher (HR=3.8; 95% PDAC cases with PrP+ tumors (median survival 5 months) compared to the 34 cases with PrP- tumors (median survival 20 months). Of 51 cases with resected, localized PDAC median survival was 74 months for 17 cases with PrP- tumors versus 14 months for 34 cases with PrP+ tumors (HR=6.7; 95% CI: 2.6, 17.4). All 6 surviving cases had PrP- negative tumors (median survival, > 10 years). PrP may have potential as a prognostic biomarker in PDAC patient management. Show more

Keywords: Pancreas, adenocarcinoma, prion, prp, prognosis, immunohistochemistry, biomarker

DOI: 10.3233/CBM-2012-0256

Citation: Cancer Biomarkers, vol. 10, no. 6, pp. 251-258, 2012

Authors: Ouerhani, Slah | Elgaaied, Amel Ben Ammar

Article Type: Research Article

Abstract: Bladder cancer is one of the most common cancers worldwide. A number of genetic and epigenetic alterations have been identified in bladder tumorigenesis, including activating mutations in fibroblast growth factor receptor 3 (FGFR3) and RAS family genes. In this study, we have analysed the mutational spectrum of FGFR3 and RAS genes (HRAS, NRAS and KRAS). We have also studied the relationship between mutations. A total of 234 patients with different stages and grades were included in the present study (58 superficial low-grade, 53 superficial high-grade and 123 muscle-invasive tumours). Mutations in exons 1 and 2 of HRAS, KRAS and NRAS …genes were screened by PCR and direct sequencing. The hot spot mutations in exons 7, 10 and 15 of the FGFR3 oncogene were studied by multiplex PCR and the SNaP-shot protocol. Overall, 8.97% (21/234) of samples were mutant for one of the RAS genes. Among these mutations 47.61% were detected in KRAS, 33.33% in HRAS and only 19.04% most frequent RAS mutations were KRAS p.G12C and p.G12D. The correlation between RAS mutations and tumour subgroups does not report a statistical significant association (p=0.876). The FGFR3 mutations were detected in 31.19% (73/234) of bladder tumours and were associated with low stages and grades. The study of relationship between RAS and FGFR3 genes revealed that FGFR3 mutations were mutually exclusive with RAS ones (p=10-4 ). In conclusion we retain that activated RAS and FGFR3 do not appear to be drivers in bladder cancer but the mutually exclusive relationship between RAS and FGFR3 mutations indicates a possible clonal advantage of modified signaling via a common pathway. Show more

Keywords: Bladder cancer, FGFR3, RAS

DOI: 10.3233/CBM-2012-0254

Citation: Cancer Biomarkers, vol. 10, no. 6, pp. 259-266, 2012

Authors: Fletcher, Nicole M. | Jiang, Zhongliang | Ali-Fehmi, Rouba | Levin, Nancy K. | Belotte, Jimmy | Tainsky, Michael A. | Diamond, Michael P. | Abu-Soud, Husam M. | Saed, Ghassan M.

Article Type: Research Article

Abstract: Objective: The study sought to identify whether a relationship exists between serum myeloperoxidase (MPO) and free iron with stages of ovarian cancer. Methods: Serum and tissue samples were collected from women with stages I through IV ovarian cancer, benign gynecologic conditions, inflammation, and healthy controls. Myeloperoxidase ELISA and VITROS Fe Slide assays were used to measure serum and tissue MPO and free iron levels, respectively. Data were analyzed with a one-way ANOVA with post-hoc comparisons (p < 0.05 considered significant). Results: There was a significant increase in the level of free iron in serum and tissues …obtained from stages II–IV as compared to early-stage (stage I) ovarian cancer. There was an overlap between early-stage and inflammation serum MPO levels, however serum free iron levels were significantly higher in early-stage. There was no significant change in serum free iron levels between non-cancer groups. In contrast, there was a significant increase in serum free iron levels in early-stage as compared to non-cancer groups. Conclusions: Collectively, these findings clearly indicate a role for the combination of serum MPO and free iron as biomarkers for early detection and prognosis of ovarian cancer. Show more

Keywords: Myeloperoxidase, free iron, ovarian cancer, biomarkers

DOI: 10.3233/CBM-2012-0255

Citation: Cancer Biomarkers, vol. 10, no. 6, pp. 267-275, 2012

Authors: Andjelkovic, Tijana | Bankovic, Jasna | Milosevic, Zorica | Stojsic, Jelena | Milinkovic, Vedrana | Pesic, Milica | Ruzdijic, Sabera | Tanic, Nikola

Article Type: Research Article

Abstract: p16 and PTEN are tumor suppressors that are commonly inactivated in human cancers. Loss of each of these molecules is widely studied in lung cancer, including non-small cell lung carcinoma (NSCLC), its most common clinical form. However, the importance of their mutual alterations for NSCLC pathogenesis has been barely examined so far. In this study we tested hypothesis that aberrant p16 might cooperate with inactive PTEN during pathogenesis of NSCLC, particularly in promoting tumor aggressiveness and invasiveness. Initially, we screened NSCLC tumor samples from patients for the presence of the most common genetic and epigenetic alterations of p16 and further …correlated them with previously detected aberrations in PTEN gene. Statistical analyses showed that aberrant p16 directly correlated with altered PTEN. Such significant correlation was also observed in groups of patients with high genomic instability, with squamocellular histological subtype, with disease grade 2 and with lymph node invasion. Finally, survival analyses revealed dramatic decrease in survival rate of patients with mutual alterations of p16 and PTEN, but without prognostic significance. Overall results implicate cooperation between aberrant p16 and PTEN in pathogenesis of NSCLC and suggest that their combination might be considered as potential molecular marker for specific subgroups of NSCLC patients. Show more

Keywords: p16, PTEN, tumor suppressors, Non-Small Cell Lung Carcinoma (NSCLC)

DOI: 10.3233/CBM-2012-0257

Citation: Cancer Biomarkers, vol. 10, no. 6, pp. 277-286, 2012

Authors: Blumenschein, Jr., George R. | Reck, Martin | Fossella, Frank | Stewart, David J. | Lathia, Chetan | Peña, Carol

Article Type: Research Article

Abstract: We investigated the relationship between plasma protein biomarker concentrations and clinical outcomes in 52 patients with relapsed/refractory advanced non-small cell lung cancer (NSCLC) treated with 400~mg bid sorafenib in a phase II trial. Blood samples were collected at baseline, on day 15 of cycle 1 (C1D15), and on day 1 of cycle 3 (C3D1), and plasma concentrations of total VEGF, VEGF-165, soluble (s) VEGFR-2, PDGF-BB, sPDGFR-β, sEGFR, sHER-2, uPA, PAI-1, uPAR, TIMP-1, and circulating Ras p21 were assayed by ELISA. Elevated baseline VEGF, VEGF-165, PDGF-BB, Ras p21, and TIMP-1 concentrations were associated with poorer patient outcomes (shorter overall survival [OS] …and/or progression-free survival [PFS]). During treatment, the mean concentrations of sVEGFR-2, PDGF-BB, sPDGFR-β, TIMP-1, uPAR, and PAI-1 decreased, while the mean sEGFR concentration increased. Increases in VEGF, VEGF-165, PDGF-BB, and TIMP-1 during treatment were associated with better outcomes (longer OS and/or PFS), whereas increases in plasma Ras p21 during treatment were associated with shorter PFS. The associations between baseline concentrations and/or pharmacodynamic changes in plasma proteins and clinical outcomes in NSCLC patients treated with sorafenib suggest that these biomarkers may have a prognostic role and/or predict the efficacy of sorafenib in patients with NSCLC. Show more

Keywords: Biomarkers, multikinase inhibitor, nonsmall cell lung cancer, sorafenib, targeted treatment

DOI: 10.3233/CBM-2012-0253

Citation: Cancer Biomarkers, vol. 10, no. 6, pp. 287-298, 2012

Article Type: Other

DOI: 10.3233/CBM-2012-10606

Citation: Cancer Biomarkers, vol. 10, no. 6, pp. 299-303, 2012