Cancer Biomarkers - Volume 7, issue 1

Authors: Vasavi, M. | Kiran, V. | RaviShankar, B. | Prabhakar, B. | Ahuja, Y.R. | Hasan, Q.

Article Type: Research Article

Abstract: Cancer development is associated with genetic instability. Identification of specific loci altered during carcinogenesis in a particular tissue gives scope for early detection and predicting the progressive nature of the tissue pathology. Instability at microsatellite loci is widely attributed to mismatch repair errors due to epigenetic alterations. Using three dinucleotide markers, D3S1313, D9S171, D17S250 and two mononucleotide markers BAT25, BATRII, we evaluated MSI in 97 cases enrolled for endoscopy of upper GI tract with symptoms of dyspepsia, reflux or dysphagia. We aimed at evaluating markers that reflect instability in esophageal malignancies, examine the prevalence of MSI in cancers and other …pathologies of the esophagus, and determine the methylation status of hMLH1 gene in relation to MSI. 42% (21/50) cancers and 15.4%(2/13) precancers exhibited MSI where 85.7% cancers and 50% precancers with MSI, showed a hypermethylated hMLH1 promoter. Increased number of cases with repair gene methylation were seen with increasing severity of the esophageal pathology suggesting epigenetic progression parallels histologic changes. BAT25 and D3S1313 markers exhibited instability frequently and cases with MSI using these markers showed an abnormal hMLH1 promoter. Thus these markers were useful in identifying the mismatch repair phenotype. These two markers may be useful to screen cases for early cancer related changes, after validation on a larger sample. Show more

Keywords: Microsatellite loci, BAT25, D3S1313, esophageal pathologies, methylation, hMLH1

DOI: 10.3233/CBM-2010-0135

Citation: Cancer Biomarkers, vol. 7, no. 1, pp. 1-10, 2010

Authors: Singh, S.K. | Grifson, J.J. | Mavuduru, R.S. | Agarwal, M.M. | Mandal, A.K. | Jha, V.

Article Type: Research Article

Abstract: Introduction: High expression of leptin receptors have been observed in the prostate cancer in various clinical studies; however the association of serum leptin with carcinoma prostate remains unresolved. We studied association, between serum leptin and carcinoma prostate in Asian (Indian) population and its association with obesity. Material and methods: 30 prospective cases of cancer prostate and 30 age matched controls were included in this study. Body mass index (BMI) was estimated and categorized in 4 groups by WHO criteria. Waist hip ratio (WHR) was calculated and divided into three groups. Serum leptin was estimated by sandwich ELISA technique …(DRG leptin ELISA kit, Marburg, Germany). Results: Both the groups were comparable for age, WHR and BMI. Serum leptin was significantly higher in patients with cancer prostate as compared to controls (median 14.18 ng/ml vs. 1.63 ng/ml; p< 0.001). The level of leptin was found to have positive correlation with BMI and WHR in controls (r=0.485, p=0.007; r=0.314, p=0.091, respectively) however, no correlation was observed in patients with cancer prostate (r=0.071, p=0.711; r=0.067, p=0.725, respectively). There was no correlation between leptin and PSA. The serum leptin level was not related to the Gleason’s score and stage of the carcinoma. Conclusions: This study shows that Prostate cancer is associated with raised serum leptin which is independent of obesity and serum PSA. It hints the role of leptin in pathogenesis of this tumor. It may not be a surrogate marker of aggressiveness. For validation, further studies including a large patient population is required. Show more

Keywords: Leptin, carcinoma prostate, obesity, body-mass-index, waist-hip-ratio

DOI: 10.3233/CBM-2010-0136

Citation: Cancer Biomarkers, vol. 7, no. 1, pp. 11-15, 2010

Authors: Srivastava, Anjali | Mousses, Spyro | Dobi, Albert | Leighton, Ximena

Article Type: Research Article

Abstract: Evaluation of gene expression profiles in CWR22 prostate tumor xenografts in nude mice revealed overexpression of the Cytochrome b561, a transmembrane electron transport protein abundant in neuroendocrine vesicles, in the castration recurrent prostate cancers (CRPC). Four fold higher levels of the Cytochrome b561 was present in highly metastatic and androgen refractory LNCaP/C4-2 prostate cancer cells in comparison to androgen responsive and non-metastatic LNCaP cells. In LNCaP cells, Cytochrome b561 expression was induced by the synthetic androgen, R1881. Of note, Cytochrome b561 expression pattern correlated with known androgen regulated genes in epithelial transcriptome of primary prostate tumors. Taken together, these novel …findings suggest that the expression of Cytochrome b561, is androgen regulated in the context of CaP cells and its increased expression in CRPC reflects increased androgen receptor signaling in tumor cells. These observations warrant further evaluation of functions and biomarker potential of Cytochrome b561 in CRPC. Show more

Keywords: Cytochrome b561, prostate cancer, CRPC, androgen, metastasis, recurrence, cell cycle

DOI: 10.3233/CBM-2010-0142

Citation: Cancer Biomarkers, vol. 7, no. 1, pp. 17-23, 2010

Authors: Li, Chen | Kim, Hye-Yeung | Vuong, Huy | Patwa, Tasneem | Pal, Manoj | Brand, Randall E. | Simeone, Diane M. | Lubman, David M.

Article Type: Research Article

Abstract: The immunogenic nature of cancer can be explored to distinguish pancreatic cancer from related non-cancer conditions. We describe a liquid-based microarray approach followed by statistical analysis and confirmation for discovery of auto-immune biomarkers for pancreatic cancer. Proteins from the Panc-1 pancreatic cancer cell line were fractionated using a 2-D liquid separation method into over 1052 fractions and spotted onto nitrocellulose coated glass slides. The slides were hybridized with 37 pancreatic cancer sera, 24 chronic pancreatitis sera and 23 normal sera to detect elevated levels of reactivity against the proteins in spotted fractions. The response data obtained from protein microarrays was …first analyzed by Wilcoxon Rank-Sum Tests to generate two lists of fractions that positively responded to the cancer sera and showed p-values less than 0.02 in the pairwise comparison between cancer specimens and normal and chronic pancreatitis specimens. The top 3 fractions with the lowest correlations were combined in receiver operating characteristic analyses. The area-under-the-curve (AUC) values are 0.813 and 0.792 for cancer vs. normal and cancer vs. pancreatitis respectively. Outlier-Sum statistics were then applied to the microarray data to determine the existence of outliers exclusive in cancer sera. The selected fractions were identified by LC-MS/MS. We further confirmed the occurrence of outliers with three proteins among cancer samples in a confirmation experiment using a separate dataset of 165 serum samples containing 48 cancer sera and 117 non-cancer controls. Phosphoglycerate kinase 1 (PGK1) elicited greater reactivity in 20.9% (10 in 48) of the samples in the cancer group, while no outlier was present in the non-cancer groups. Show more

Keywords: Pancreatic cancer, microarray, humoral response, PGK, Panc-1, Outlier-sum

DOI: 10.3233/CBM-2010-0145

Citation: Cancer Biomarkers, vol. 7, no. 1, pp. 25-37, 2010

Authors: Bermano, G. | Smyth, E. | Goua, M. | Heys, S.D. | Wahle, K.W.J.

Article Type: Research Article

Abstract: Breast cancer aetiology is unclear despite comprising approximately 28% of female cancers. Several risk factors are known. Not all women exhibiting established risk factors will develop breast cancer but many without recognised risk factors will, indicating involvement of unknown risk factors. Impaired basal or oxidation-stimulated gene expression of redox enzymes, particularly Glutathione Peroxidase 1 and 4 (GPX1 and 4), resulting in increased oxidative stress, could be an “unknown” risk factor in breast cancer. We determined whether basal expression of GPX1 and 4, two major redox enzymes, in Peripheral Blood Mononuclear Cells (PBMNC) and/or their stimulated expression (oxidative stress) …was impaired in women with breast cancer who have no known markers of risk compared with control women without breast cancer. A significant 30% impairment (p< 0.01) in basal PBMNC GPX4, but not GPX1, gene expression was observed in cancer patients. Oxidative stress stimulation in vitro did not increase GPX4 expression significantly in cancer patients or control women whereas GPX1 expression was significantly increased (30%, p<0.05) only in the cancer group. Attenuation of GPX4 mRNA expression in PBMNC suggests this could be a simple,early biomarker for future breast cancer risk in the high proportion of women without known risk factors who eventually contract the disease. Show more

Keywords: Breast cancer risk, gene expression, GPX1, GPX4, PBMNC, oxidative stress

DOI: 10.3233/CBM-2010-0146

Citation: Cancer Biomarkers, vol. 7, no. 1, pp. 39-46, 2010

Authors: Nicotra, Giuseppina | Castino, Roberta | Follo, Carlo | Peracchio, Claudia | Valente, Guido | Isidoro, Ciro

Article Type: Review Article

Abstract: Three molecular forms of the proteolytic enzyme Cathepsin D (CD) are found in the cell: the precursor (proCD), the intermediate single-chain and the mature double-chain. ProCD, which is found in the Golgi Complex, is enzymatically inactive, while the intermediate and the mature forms, respectively found in endosomes and lysosomes, are enzymatically active. The latter are involved in autophagy and apoptosis pathways thus playing a crucial role in the control of cell and tissue homeostasis. ProCD can be secreted in the extracellular space and, by interacting with membrane receptors, can promote cell proliferation. At slightly acid pH, secreted proCD undergoes partial …maturation and becomes active. In the extracellular space, CD can degrade the protein components of the matrix and free growth factors therein embedded, thus favoring tumor growth, invasion and angiogenesis. Based on the multiple tasks performed by CD inside and outside the cell, it is not irrational to hypothesize its involvement in cancer development and progression and a strict link between its tissue expression and the clinico-pathological features of the tumor. Thus, not surprisingly, as many as 519 articles are found in the database of pubmed with the keywords ‘cathepsin D, cancer and marker’. Disappointingly, however, in spite of, or because of, this large number of studies, the scientific community has not reached a general agreement on the prognostic value of CD in cancer progression. Here, we will briefly review the relevant literature and offer a possible explanation for the conflicting data. Show more

Keywords: Lysosome, tumor marker, prognosis, metastasis, proteolysis, cell death

DOI: 10.3233/CBM-2010-0143

Citation: Cancer Biomarkers, vol. 7, no. 1, pp. 47-64, 2010