Cancer Biomarkers - Volume 6, issue 2

Authors: Samy, Nervana | Ragab, Halla M. | El Maksoud, Nabila Abd | Shaalan, Mohamed

Article Type: Research Article

Abstract: Breast cancer is the most common malignancy in women, options for treatment of breast cancers are complex and varied, there is a need for biological prognostic indicators that would, alone or in combination with others, be sufficient to predict disease recurrence and hence, the basis for supplemental treatment after local therapy. The aim of this study was to determine prognostic significance of serum Her2/neu, BCL2, CA 15-3 and CEA during the follow-up of the patients with breast cancer, also, to investigate the association between these biomarkers and clinicopathological parameters and patient outcomes in breast cancer. Patients …and methods: Eighty nine patients with breast cancer stage I and II are enrolled in our study. Their age ranged from 35–59 years. Patients underwent radical mastectomy or breast-conserving surgery with axillary lymph node dissection. After the surgical treatment they had supplementary therapy. The size of the tumor was < 2 cm in 35 patients and > 2 cm in 54 patients. Their histological type was invasive duct carcinoma, 49 patients had lymph node positive and 40 had negative lymph node. Nine patients had recurrence of the disease during the 18 months of follow up. BCL2, Her2/neu, CEA and CA15-3 in sera had been monitored by ELISA before and after operation, every 6 months and at the time of diagnosis of first recurrence for 18 months. Results: Preoperative serum levels of Her2/neu, BCL2, CA15-3 and CEA were significantly higher compared with the levels of the control group, these markers dropped significantly after operation. Univariate analysis of parameters associated with relapse showed that the clinicopathological factors (histologic grade, tumor stage and lymph nodes) and serum markers (HER2/neu, BCL2, CA15-3 and CEA) were significantly associated with recurrence of disease. Multivariate analysis of investigated parameters revealed that tumor stage, lymph nodes and serum tumor markers were significant variables predicting recurrence of tumor. Conclusion: Serum Her2/neu, BCL2, CA15-3 and CEA in breast cancer patients were useful markers for predicting aggressive behaviorof tumor and elevated serum levels are associated with breast cancer relapse. Our relatively small study population limits the predictive power of the panels presented here, but the benefits of a serum biomarker and multimarker approach are clearly illustrated and further studies utilizing larger clinical cohorts are well warranted. Show more

Keywords: Breast Cancer, Her2/neu, BCL2, CA15-3, CEA

DOI: 10.3233/CBM-2009-0119

Citation: Cancer Biomarkers, vol. 6, no. 2, pp. 63-72, 2010

Authors: Callesen, Anne K. | Madsen, Jonna S. | Iachina, Maria | Vach, Werner | Kruse, Torben A. | Jensen, Ole N. | Mogensen, Ole

Article Type: Research Article

Abstract: In the present study, the use of a robust and sensitive mass spectrometry based protein profiling analysis was tested as diagnostic tools for women with an ovarian tumor. The potential additional diagnostic value of serum protein profiles independent of the information provided by CA125 were also investigated. Protein profiles of 113 serum samples from women with an ovarian tumor (54 malign and 59 benign) were generated using MALDI-TOF MS. A total of 98 peaks with a significant difference (p< 0.01) in intensity between women with benign tumors/cysts and malignant ovarian tumors were identified. After average linkage clustering, a …profile of 46 statistical significant mass peaks was identified to distinguish malignant tumors and benign tumors/cysts. In the subgroup of women with normal CA125 values (⩽ 35 U/mL) (62 patients) 36 of the 504 mass peaks showed significant (p< 0.05) differences in intensity between benign and malignant disease. After average linkage clustering, 25 statistical significant mass values were identified in this clinical difficult and important subgroup presenting with normal CA125 values. The current study demonstrates the potential of mass spectrometry based serum protein profiling as a diagnostic tool in discrimination between benign ovarian tumors/cysts and malignant ovarian tumors. Additionally, the method provided diagnostic information independent of CA125. Show more

Keywords: Protein profiling, proteomics, ovarian cancer, MALDI TOF MS, serum

DOI: 10.3233/CBM-2009-0120

Citation: Cancer Biomarkers, vol. 6, no. 2, pp. 73-82, 2010

Authors: Kumar, Kalyana | Vamsy, Mohana | Jamil, Kaiser

Article Type: Research Article

Abstract: Our study supports the Drug-Gene Interaction principle, where patients experience adverse drug reactions (ADRs) due to genetic predisposition or due to single nucleotide polymorphisms (SNPs) in drug metabolizing genes. The target enzyme for 5- Fluorouracil is thymidylate synthase (TYMS) this enzyme is also involved in folate metabolism. We determined the frequencies of polymorphisms in drug metabolizing enzyme like TYMS and correlated the drug response in 140 breast cancer patients compared to 150 controls, using PCR and RFLP method. In our results the TYMS1494del polymorphism was statistically significant; allele frequencies for 6bp deletion and 6bp insertion were 0.85 and 0.15 in …BC (Breast Cancer) patients compared with 0.95 and 0.04 in controls. The enhancer region 2R/3R heterozygote genotypes were found to be not significant for BC risk. In this study combined genotypes showed 2 fold increased risk of BC. Frequency distribution of 2R and 3R allele among BC patients was 0.85 and 0.15 and 0.95 and 0.04 in controls respectively. Correlation analysis of TYMS enhancer region polymorphisms with drug response suggested that the response was poor in BC patients with 2R/3R and 2R/2R genotypes, but patients with poor response were fewer in number, that this gene may be important in drug response. Genetic screening of the drug metabolizing enzyme like TYMS for the presence of polymorphisms in breast cancer patients will become increasingly useful in individualizing drug therapy. Show more

Keywords: TYMS: Thymidylate Synthase, ADRs: Adverse Drug Reaction, BC: Breast cancer

DOI: 10.3233/CBM-2009-0121

Citation: Cancer Biomarkers, vol. 6, no. 2, pp. 83-93, 2010

Authors: Goswami, Binita | Rajappa, Medha | Gupta, Nikhil | Mahto, Mala | Hadke, Niladhar S. | Mishra, Tarun Kumar

Article Type: Research Article

Abstract: Objectives: Oxidative stress and pro-inflammatory mediators have been implicated in breast carcinogenesis. We attempted to evaluate the markers of oxidative stress, antioxidant mechanism and the inflammatory pathway in patients with breast cancer. Methods: This study was carried out in departments of Biochemistry and Surgery, Maulana Azad Medical College and associated Hospitals, New Delhi, India. A total of 60 cases of carcinoma of the breast and 60 healthy controls were included in the study. The parameters that were assayed include markers of oxidative stress-conjugated dienes, thiobarbitone reactive substances (TBARS), antioxidants-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) …and markers of inflammation-interleukin-6(IL-6) and ferritin. Results: There was a significant decline in the antioxidant levels and a significant rise in oxidant levels in patients with carcinoma of the breast, compared to controls. The inflammatory markers-IL-6 and ferritin-were also significantly higher in patients with breast cancer. A significantly positive correlation was observed between the IL-6 levels and conjugated dienes with the stage of breast carcinoma; whilst a significantly negative correlation was observed between the levels of conjugated dienes and superoxide dismutase and superoxide dismutase levels with the disease staging. Conclusions: This study underlines the interplay between inflammatory pathways and oxidative stress in the pathogenesis of breast cancer. Mini Abstract: An intense research is underway to identify the possible risk factors and the molecular mechanisms involved in pathogenesis of breast cancer. Inflammation and oxidative stress are two such etiologies investigated in our study. Show more

Keywords: Breast cancer, oxidative stress, conjugated dienes, thiobarbitone reactive substances (TBARS), antioxidants, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase(Gpx), glutathione(GSH), inflammation, interleukin-6(IL-6) and ferritin

DOI: 10.3233/CBM-2009-0122

Citation: Cancer Biomarkers, vol. 6, no. 2, pp. 95-103, 2010

Authors: Mahmoud, Moushira A. | Ali, Mohamed H. | Hassoba, Howayda M. | Elhadidy, Gehan S.

Article Type: Research Article

Abstract: Background: Bladder cancer is a major health problem in Egypt as it represents the most common malignancy. Aim: Evaluation of the potential usefulness of serum IL-8 and IGF-1 in Egyptian bladder cancer patients. Methods: Serum levels of IL-8 and IGF-1 were determined in 51 bladder cancer patients and 45 controls using a chemiluminescence enzyme immunometric assay. Results: Serum IL-8 was significantly higher in cancer patients than in controls (P < 0.0001). It was significantly higher in patients with invasive cancer than those with superficial cancer (P < 0.01). Also, IL-8 showed a significant elevation …in relation to schistosomal infection (P = 0.02) however, it did not differ in relation to either pathological type of tumor or its grade (P > 0.05). Receiver operating characteristic (ROC) curve indicated that IL-8 cut-off value of 35 pg/mL yielded the best combination of sensitivity (71%) and specificity (98%) for differentiating patients with bladder cancer from control subjects. Serum IGF-1 levels showed no significant difference between bladder cancer patients and controls (P > 0.05). There was no relationship between IGF-1 levels and clinicopathological parameters. Conclusions: In Egyptian patients with bladder cancer, serum IL-8 is significantly elevated and its level is related to tumor invasion and associated schistosomal infection. Moreover, serum IGF-1 level does not help as a serum tumor marker in these patients. Show more

Keywords: Interleukin-8, insulin like growth factor-1, bladder cancer, schistosomal infection

DOI: 10.3233/CBM-2009-0133

Citation: Cancer Biomarkers, vol. 6, no. 2, pp. 105-110, 2010

Authors: Lee, Gregory | Ge, Bixia | Huang, Teng-Kai | Zheng, Gary | Duan, Jiantao | Wang, Ida Hsiao Yun

Article Type: Research Article

Abstract: Background: Background: To evaluate the clinical utility of CA215 as a pan cancer biomarker, serum levels of CA215 were determined with clinically defined serum specimens from over 500 cancer patients and compared with results obtained by other nine established cancer markers. The molecular nature of this cancer-associated antigen from selected patients' sera was determined. Methods: Methods: By using improved immunoassays, serum levels of CA215 and other known biomarkers were determined for respective positive detection rates. The molecular size of CA215 from cancer patients was determined by Western blot assay. Results: Results: By using 0.1 AU/ml as …the normal cut-off value, the positive rates of CA215 for different cancers were shown to be 52% (lung), 74% (liver), 44% (colon), 61% (esophagus), 60% (stomach), 59% (ovary), 40% (prostate), 71% (breast), 38% (kidney), 41% (pancreas), 51% (cervix), and 83% (lymphoma), respectively. Other cancer markers including AFP, CEA, CA125, CA19-9, CA15-3, Cyfra21-1, Ferritin, β2 microglobulin and PSA were also parallelly compared. A combination of CA215 with other tissue-associated cancer markers generally resulted in much higher cancer detection rates. CA215 detected from cancer patients was confirmed to be human immunoglobulins that contain common RP215-specific carbohydrate-associated epitope. Conclusion: Conclusion: Through clinical evaluations of serum specimens of various cancer patients, CA215 was confirmed to be human cancer cell-derived immunoglobulins. CA215 is apparently comparable to or better than other known biomarkers for the positive detection and monitoring of many types of human cancers. Show more

Keywords: CA215 pan cancer biomarker, enzyme immunoassay, western blot assay, cancer cell-derived immunoglobulins, RP215 monoclonal antibody

DOI: 10.3233/CBM-2009-0134

Citation: Cancer Biomarkers, vol. 6, no. 2, pp. 111-117, 2010