Cancer Biomarkers - Volume 11, issue 5

Authors: Khaled, Yazan S. | Elkord, Eyad | Ammori, Basil J.

Article Type: Review Article

Abstract: Background and aims: The macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the transforming growth factor-β (TGF-β ) superfamily that can serve as a potential immune-therapeutic target and/or a prognostic biomarker for the treatment of some cancers. This article reviews the current published data on the molecular and clinical application of MIC-1 in cancer. Methods: Literature review was conducted using Medline, PubMed, Embase and Cochrane databases. Results: MIC-1 is the only known secreted p53-regulated cytokine and therefore can serve as a biomarker for p53 activation both in vitro and in vivo. MIC-1 gene can …be activated by cyclooxygenase inhibitors and has pro-apoptotic and anti-tumour activities. Although MIC-1 may induce anti-tumour role in the early stages of cancer, it can promote the invasiveness and metastatic behaviour in advanced stages. Greater concentration of MIC-1 was associated with the induction of cancer-related anorexia and weight loss in animals and humans. Of clinical interest, MIC-1 out-performs all available biomarkers including CA19-9 in the differentiation of patients with resectable pancreatic cancer from patients with benign pancreatic disease. MIC-1 gene was over-expressed in colorectal cancer (CRC), and a progressive rise of MIC-1 serum levels was noted in patients with adenomatous polyps and further in patients with CRC. Conclusions: MIC-1 cytokine has the potential characteristics for a new diagnostic biomarker and a target for cancer treatment. Further research however is required to characterise MIC-1 receptors and to revalidate its diagnostic power in larger and better-standardised clinical studies. Show more

Keywords: Macrophage Inhibitory Cytokine -1, pleiotropic, pancreatic, colorectal, cancer

DOI: 10.3233/CBM-2012-00287

Citation: Cancer Biomarkers, vol. 11, no. 5, pp. 183-190, 2012

Authors: Mentese, Ahmet | Fidan, Evren | Sumer, Aysegül Uzun | Karahan, Süleyman Caner | Sonmez, Mehmet | Altay, Diler Us | Kavgaci, Halil | Alver, Ahmet

Article Type: Research Article

Abstract: Purposes: This study was intended to determine the diagnostic significance of signal peptide-CUB-EGF domain-containing protein 1 (SCUBE 1) levels in gastric cancer. Methods: This retrospective study was conducted with patients with gastric cancer. SCUBE 1 titers of plasma in patients with gastric cancer were determined using an enzyme-linked immunosorbent assay (ELISA). Results: SCUBE 1 titers of gastric cancer patients were significantly higher compared with the control group (P=0.0001). At a SCUBE 1 cut-off point of 43 ng/mL, sensitivity was 67%, specificity 91%, positive predictive values (PPV) 92% and negative predictive values(NPV) 63%. SCUBE 1 levels of …patients with methastase were not different from patients without methastase (P> 0.05). Dicussions: SCUBE 1 levels in patients with gastric cancer were found higher compared to healthy subjects. Show more

Keywords: SCUBE 1, gastric cancer, biomarker

DOI: 10.3233/CBM-2012-00285

Citation: Cancer Biomarkers, vol. 11, no. 5, pp. 191-195, 2012

Authors: Tajnik, Mojca | Stražišar, Mojca | Volavšek, Metka | Boštjančič, Emanuela | Glavač, Damjan

Article Type: Research Article

Abstract: The study focuses on BBC3 gene expression in primary head and neck squamous cell carcinomas (HNSCC) in relation to pTNM classification. We used quantitative real-time PCR on 35 biopsy samples of HNSCC tumor samples to evaluate differences of BBC3 expression depending on tumor size, regional lymph node involvement, location and tumor staging. In order to confirm the model of BBC3-mediated apoptosis, we used immunohistochemistry to determine the expression of apoptotic proteins p53, p63, Bcl-2 and Bax. We also used publicly available cDNA microarray datasets. Our results show a general down-regulation of BBC3 in tumor tissue compared to adjacent normal tissue. …The expression was significantly altered among different groups of patho-histologically evaluated tumor sizes, but not in relation to tumor location, regional lymph node involvement or tumor stage. That suggests the potential use of BBC3 as a new tumor size marker in HNSCC. Through protein expression analysis combined with publicly available cDNA microarray datasets of apoptotic factors, we confirmed the model of BBC3-mediated apoptosis, which can be activated with or without p53. Show more

Keywords: Head and neck cancer, pTNM classification, BBC3, tumor size, p53, apoptosis

DOI: 10.3233/CBM-2012-00286

Citation: Cancer Biomarkers, vol. 11, no. 5, pp. 197-208, 2012

Authors: Paiva, Carlos Eduardo | Serrano, Sérgio Vicente | Paiva, Bianca Sakamoto Ribeiro | Scapulatempo-Neto, Cristovam | Soares, Fernando Augusto | Rogatto, Silvia Regina | Marques, Mariângela Esther Alencar

Article Type: Research Article

Abstract: In the case of operated breast cancer (BC), prognostic markers help to determine if the patient needs additional treatment and predictive markers help the clinician to decide which treatment to use. Thus, a better knowledge of known predictive and prognostic markers and the identification of new markers, may improve the treatment of BC patients. The transforming growth factor-beta type II receptor (TGF-βRII), a main receptor of transforming growth factor beta pathway, is a potential new prognostic marker. The aims of the present study were to investigate both the predictive and prognostic impact of TGF-βRII in BC samples. TGF-βRII protein expression …was evaluated using immunohistochemistry on a tissue microarray containing 110 TNM stage III BC samples obtained prior to doxorubicin-based neoadjuvant chemotherapy (NAC). Our results demonstrate that TGF-βRII did not predict the response to NAC. On the other hand, an association between TGF-βRII-negative tumor and higher risk of metastasis to lungs and bones was verified. TGF-βRII negativity was an independent prognostic factor for decreased disease-free and overall survival. Show more

Keywords: Breast cancer, survival, TGF-βRII, metastasis, prognostic marker

DOI: 10.3233/CBM-2012-00281

Citation: Cancer Biomarkers, vol. 11, no. 5, pp. 209-217, 2012

Authors: Lu, Yuanming | Jingyan, Gao | Baorong, Song | Peng, Junjie | Xu, Ye | Cai, Sanjun

Article Type: Research Article

Abstract: Background: As key molecules that drive progression and chemoresistance in gastrointestinal cancers, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (Her2) have become efficacious drug targets in this setting. But until now, although above studies suggested that EGFR and Her2 may serve as effective biomarkers for targeted therapy in cancer patients with primary tumor, the information on these biomarkers in colorectal cancer is still limited in metastases. Objective: The purpose of this study is to evaluate the expression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (Her2) on the …lymph node metastasis (LNM) of colorectal cancer (CRC), develop LNM-associated biomarkers for CRC. Methods: Differences in EGFR and Her2 expression between primary CRC with LNM (LNM CRC) and without LNM (non-LNM CRC) were assessed in a total of 126 Chinese colorectal carcinoma samples using quantitative real-time PCR analysis and western blot. Confirmation assay with immunohistochemistry (IHC) study was applied in the same samples. The relationship to clinicopathological parameters and prognosis of candidate biomarkers was also examined in the same samples. Results: EGFR and Her2 were significantly upregulated in LNM CRC compared to non-LNM CRC, which was confirmed by real-time quantitative polymerase chain reaction, western blot. Similar results were confirmed in the immunohistochemistry (IHC) assay. Overexpression of EGFR and Her2 were significantly associated with LNM (P < 0.001), advanced TNM stage (P < 0.001), increased 5-year recurrence rate (P < 0.001) and decreased 5-year overall survival rate (P < 0.001). Univariate and multivariate analyses indicated that EGFR and Her2 expression were useful independent prognostic factor for recurrence and survival of CRC patients (P < 0.05). Conclusions: EGFR and Her2 might serve as a potential biomarker for LNM and a prognostic factor in CRC. Over-expression of EGFR or Her2 is a potential predict factor to the poor outcome in clinical colorectal cancer. Show more

Keywords: Colorectal cancer, lymph node metastasis, prognosis, quantitative real-time PCR analysis, EGFR, Her2

DOI: 10.3233/CBM-2012-00282

Citation: Cancer Biomarkers, vol. 11, no. 5, pp. 219-226, 2012