Cancer Biomarkers - Volume 2, issue 6

Authors: Ziv, Tamar | Barnea, Eilon | Segal, Hava | Sharon, Rivka | Beer, Ilan | Admon, Arie

Article Type: Research Article

Abstract: Small cell lung carcinoma (SCLC) is an aggressive, highly metastatic cancer with a strong tendency for chemotherapy resistance. Identification of proteins uniquely expressed in SCLC cells, can facilitate the development of new diagnostic tools, improve immunotherapy, and deepen our understanding of the underlying mechanisms of the disease. Here we describe a comparative proteomics analysis of ten SCLC cell lines and three controls lines, while searching for proteins preferentially expressed in SCLC cells as potential disease markers. Total protein extracts were compared by two-dimensional gel electrophoresis and by two-dimensional liquid chromatography resulting in the identification of 1093 proteins, 202 of which …were detected only in the SCLC cells. These include proteins of different cellular functions, including cellular proliferation and known tumor antigens. Since SCLC has a neuroendocrine origin, of major interest are the identified proteins involved in nerve and brain embryonic development. These proteins are potentially valuable as both tumor markers and as antigens for immunotherapy. Show more

Keywords: Proteomics, small cell lung carcinoma, mass spectrometry, two-dimensional gel electrophoresis, two-dimensional liquid chromatography, cancer proteins

DOI: 10.3233/CBM-2006-2601

Citation: Cancer Biomarkers, vol. 2, no. 6, pp. 219-234, 2006

Authors: Gast, M.C.W. | Bonfrer, J.M.G. | van Dulken, E.J. | de Kock, L. | Rutgers, E.J.Th. | Schellens, J.H.M. | Beijnen, J.H.

Article Type: Research Article

Abstract: There is an urgent need for new serum markers that can be applied in e.g. the early detection of breast cancer. Following detection of new, potential biomarkers, such as those reported by Vlahou et al. (Clin Breast Cancer 2003;4:230–239) and Laronga et al. (Dis Markers 2003;19:229–238), assessment of both their robustness and validity is essential to confirm their clinical applicability. We therefore aimed to determine robustness and validity of biomarkers reported by the authors mentioned, by analysis of an independent sample set (breast cancer: n=47, normal women: n=45) in our laboratory, according to the methods described by both authors. Although …all markers for the differentiation between breast cancer patients and normal women, discovered in the study of Vlahou et al., were recovered in our validation data set, none had sufficient performance to be applied as a classifier. The markers discovered by Laronga et al. in the differentiation between lymph node positive and -negative breast cancer patients were in part recovered from our validation data set, but were also not applicable as a classifier. In conclusion, although (part of) the proteins discovered and designated as markers by either author could be detected, their validity as biomarkers could not be confirmed by the current study. This finding stresses that, when reporting on a potential biomarker, confirmation of both robustness and validity is essential in obtaining its true clinical applicability. Show more

Keywords: Biomarkers, robustness, validity, SELDI-TOF MS, breast cancer

DOI: 10.3233/CBM-2006-2602

Citation: Cancer Biomarkers, vol. 2, no. 6, pp. 235-248, 2006

Authors: Kohli, Manish | Siegel, Eric | Bhattacharya, Sudeepa | Khan, Mir Alikhan | Shah, Rajesh | Suva, Larry J.

Article Type: Research Article

Abstract: Prostate cancer frequently progresses despite early diagnosis and appropriate treatment with radical prostatectomy and/or radiotherapy. The clinical utility of SELDI-TOF MS to identify serum biomarker patterns associated with prostate cancer progression was examined by analysis of the serum proteome of advanced prostate cancer patients receiving standard androgen deprivation therapy. Serum from advanced-stage patients receiving androgen deprivation therapy was profiled by SELDI-TOF MS. Group 1 patients (n=15) had stable prostate specific antigen (PSA) responses to treatment; Group 2 (n=16) had rising PSA levels. Spectra were subjected to peak identification following total ion current (TIC) normalization. Peak intensities with m/z between 2,000 …and 20,000 were tested for group differences via Kruskal-Wallis tests, and assessed individually for PSA-independent associations with overall survival via covariate-adjusted Cox regressions. TIC normalization yielded 53 useable spectra; 119 peaks with m/z between 2,000 and 20,000 were identified. Seven peaks showed statistically significant (p<0.05) differences between PSA groups, and several other peaks showed significant associations with overall survival independent of PSA status. In summary, SELDI-TOF MS captured a specific biomarker profile associated with biochemical relapse and provided additional prognostic information regarding long-term survival, independent of clinical PSA status. Show more

Keywords: Advanced disease, hormone-sensitive, prostatic neoplasm, proteomics

DOI: 10.3233/CBM-2006-2603

Citation: Cancer Biomarkers, vol. 2, no. 6, pp. 249-258, 2006

Authors: Piyathilake, Chandrika J. | Azrad, Maria | Jhala, Darshana | Macaluso, Maurizio | Kabagambe, Edmond K. | Brill, Ilene | Niveleau, Alain | Jhala, Nirag | Grizzle, William E.

Article Type: Research Article

Abstract: The purpose of this study was to evaluate whether mandatory fortification of grain products with folic acid in the USA is associated with changes in global DNA methylation in cells involved in cervical carcinogenesis. Archived specimens of cervical intraepithelial neoplasia (CIN) diagnosed before (1990–92) and after mandatory folic acid fortification (2000–02) were used to examine for global DNA methylation in specific lesions involved in cervical carcinogenesis by using a monoclonal antibody specific for 5 methyl cytosine (5-mc). The total number of lesions examined was 152 in the pre-fortification period and 172 in the post-fortification period. Immunohistochemical staining for 5-mc, the …assessment of methylation status and data entry were blinded with regard to the fortification status. Age- and race-adjusted mean percentage of cells positive for 5-mc or the 5-mc score was not significantly different (P>0.05) between the pre- and post fortification periods in any of the individual lesions evaluated (i.e., normal cervical epithelium, reactive cervical epithelium, metaplastic cervical epithelium, CIN or carcinoma in situ). The degree of global DNA methylation was significantly higher (P<0.0001) in ⩾ CIN 2 lesions compared to ⩽ CIN 1 lesions, regardless of the fortification group. These results suggest that mandatory fortification with folic acid in the United States has not resulted in a change in the degree or the pattern of global DNA methylation in cells involved in cervical carcinogenesis. Show more

Keywords: Folic acid, fortification, DNA, methylation, cervix

DOI: 10.3233/CBM-2006-2604

Citation: Cancer Biomarkers, vol. 2, no. 6, pp. 259-266, 2006