Cancer Biomarkers - Volume 13, issue 5

Authors: Tsai, Meng-Shu | Kuo, Min-Liang | Chang, Cheng-Chi | Wu, Ying-Tai

Article Type: Research Article

Abstract: Background: Vascular endothelial growth factor (VEGF) affects tumor growth and metastasis by mediating angiogenesis. Vascular endothelial growth factor overexpression is considered a predictor of poor prognosis in cancer patients. Exercise may increase the circulating levels of VEGF, which is important to angiogenesis. We examined the effects of exercise training on VEGF levels and tumor growth in male C57BL/6 mice inoculated with Lewis lung cancer cells. Methods: Thirty-two mice were randomly assigned to either the tumor control (TC, n=16) group or the tumor exercise (TE, n=16) group. Half of the mice in TE group received aerobic interval exercise training, …and the other half received aerobic continuous exercise training for 4 weeks. The animal weights and tumor volumes were assessed three times per week. Serum VEGF levels were determined at baseline, 2 and 4 weeks. The solid tumor, lung and liver were excised and evaluated at study completion. Results: There was a significant increase in VEGF levels after the 4-week exercise training program in TE group, but no significant changes were observed in TC group. Conclusions: Although exercise training increased serum VEGF levels, group differences were not evident in our study. Exercise training did not alter the survival rate or tumor growth in tumor-bearing mice. Show more

Keywords: Exercise training, tumor growth, vascular endothelial growth factor

DOI: 10.3233/CBM-130359

Citation: Cancer Biomarkers, vol. 13, no. 5, pp. 307-313, 2013

Authors: Chen, Chao | Liu, Jianhua | Xu, Guoxiong

Article Type: Research Article

Abstract: Background: PIWI proteins belong to the Argonaute family. The human PIWI subfamily genes encode four PIWI (also known as PIWI-like) proteins: PIWIL1, PIWIL2, PIWIL3, and PIWIL4. The dysregulated expression of PIWI proteins appears to be associated with tumorigenesis. Objective: To explore the expression of PIWI proteins in primary and metastatic tumors from patients with stage III epithelial ovarian cancer (EOC), evaluate the diagnostic value of PIWI in various tissues, and analyze the characteristics of each PIWI protein associated with metastasis. Methods: A total of 20 patients with stage III EOC were retrieved for the present study. …Various tissues from the primary tumor, adjacent normal tissue, peritoneal metastasis, and lymph node with or without metastasis were examined. PIWI proteins were detected by immunohistochemistry using tissue microarray and analyzed. Results: PIWIL1, PIWIL2, PlWlL3, and PIWIL4 were expressed in EOC. By comparison with the adjacent normal tissues, the expression of four PIWI proteins was significantly enhanced in the primary tumor and metastatic tissues (P< 0.01). Conclusion: PIWI proteins are upregulated in EOC and associated with metastasis. These proteins may be useful as diagnostic biomarkers for EOC. The function of PIWI proteins in EOC with tumor metastasis will need to be further explored. Show more

Keywords: PIWI protein, epithelial ovarian cancer, metastasis

DOI: 10.3233/CBM-130360

Citation: Cancer Biomarkers, vol. 13, no. 5, pp. 315-321, 2013

Authors: Xuan, Shi-Hai | Zhou, Yu-Gui | Pan, Ji-Qun | Zhu, Wei | Xu, Ping

Article Type: Research Article

Abstract: Background: Integrins are cell-surface adhesion molecules, regulate normal cellular interactions, and which are consisting of α and β subunits and facilitate signal transduction in a bidirectional manner. Tumor cells have been found to express a wide variety of integrins, overexpression of integrin α v has been detected in a growing number of human malignancy types, However, the reports obout expression of integrin α v in nasopharyngeal carcinoma (NPC) are very rare. Objective: This study aims to detect the expression of integrin α v in NPC, and to evaluate the correlation between integrin α v expression and …clinicopathological factors. Methods: Real-time polymerase chain reaction (real-time PCR) assay and immunohistochemical staining were performed to detect the expression of integrin α v in NPC tissue samples. The correlation between the integrin α v expression and clinicopathological factors was evaluated. Results: In NPC tissues, the expression levels of integrin α v mRNA was significantly higher than those in the nasopharyngeal inflammation tissues (P< 0.05), and the expression level were significantly correlated with T, N and clinical stage (all P < 0.05). Moreover, the expression rates of integrin α v protein in NPC tissues was 76.92%, significantly higher than that of nasopharyngeal inflammation tissues (6.25%, P< 0.05). We also observed that the protein expression of integrin α v was significantly related to T, N and clinical stage (all P< 0.05). Conclusions: All these findings suggest that overexpression of integrin α v is closely associated with metastasis and progression of NPC. Therefore, we can speculate that integrin α v could be effective prognostic markers in the future for individualized treatment of patients with NPC. Show more

Keywords: Integrin, nasopharyngeal carcinoma, metastasis, progression

DOI: 10.3233/CBM-130361

Citation: Cancer Biomarkers, vol. 13, no. 5, pp. 323-328, 2013

Authors: Ju, Lixia | Zhou, Caicun

Article Type: Research Article

Abstract: We have previously shown that integrin β1 associates with gefitinib resistance. As epithelial-mesenchymal transition (EMT) also induces gefitinib resistance in vitro, we wished to determine the relation of them in gefitinib resistance. In this study, we show that integrin β1 induced epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in xenograft tumors and gefitinib-resistant NSCLC tumors acquired EMT phenotype. Furthermore, inhibition of integrin β1 reverses EMT, meanwhile overexpression and activation of integrin β1 aggravates EMT. Lastly, we further identified that integrin β1 enhanced EMT via FAK-AKT signaling pathway. These findings highlight a novel relation of integrin β1 and …EMT in EGFR TKI resistant NSCLC. Show more

Keywords: Integrin beta 1, epidermal-mesenchymal transition, EGFR TKI, resistance, non-small cell lung cancer

DOI: 10.3233/CBM-130362

Citation: Cancer Biomarkers, vol. 13, no. 5, pp. 329-336, 2013

Authors: Li, Haibo | Tang, Kui | Niu, Lizhi | Liang, Yingqing | Li, Jialiang | Chen, Jibing | Xu, Kecheng

Article Type: Research Article

Abstract: Carcinoembryonic antigen (CEA) is a prognostic marker for early-stage non-small cell lung cancer (NSCLC), and cryoablation is a new therapeutic alternative for lung cancer. We determined whether cryoablation-induced changes in serum CEA levels correlated with tumor type (adenocarcinoma or squamous carcinoma) and treatment type (comprehensive therapy [cryoablation of all intra- and extrapulmonary tumors] or palliative therapy [cryoablation of only extrapulmonary tumors]) in patients with metastatic NSCLC, and assessed whether pre-treatment CEA levels predicted overall survival (OS). We retrospectively reviewed the clinical data of 88 patients with metastatic NSCLC who underwent comprehensive (62 patients) or palliative (26 patients) therapy. Pre- and …post-cryoablation serum CEA levels and overall survival were determined for all patients. Cryoablation significantly reduced CEA levels in adenocarcinoma, but not squamous carcinoma, patients. Among adenocarcinoma patients, the cryoablation-induced reduction in CEA levels was significantly greater after comprehensive treatment than after palliative treatment; the OS of patients under comprehensive cryoablation was longer than those under palliative treatment. Among adenocarcinoma patients receiving comprehensive cryoablation, OS was significantly longer in those with normal pre-treatment serum CEA levels than in those with abnormal pre-treatment serum CEA levels. Pretreatment level and change of serum CEA can be a good indicator for therapeutic effects and OS in metastatic NSCLC patients under percutaneous cryosurgery. Show more

Keywords: Cryosurgery, carcinoembryonic antigen, metastatic non-small cell lung cancer

DOI: 10.3233/CBM-130368

Citation: Cancer Biomarkers, vol. 13, no. 5, pp. 337-343, 2013

Authors: Liu, Shuang | Zhu, Pengfei | Zhang, Ling | Ding, Shanlong | Zheng, Sujun | Wang, Yang | Lu, Fengmin

Article Type: Research Article

Abstract: Background: Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) has been widely used to quantify relative gene expression because of the high specificity, sensitivity and accuracy of this technique. However, its reliability is strongly depends on the expression stability of reference gene used for data normalization. Therefore, identification of reliable and condition specific reference genes is critical for the success of RT-qPCR. Objective: Hepatitis B virus (HBV) infection, male gender and the presence of cirrhosis are widely recognized as the leading independent risk factors for the development of hepatocellular carcinoma (HCC). This study aimed to select reliable reference …gene for RT-qPCR analysis in HCC patients with all of those risk factors. Methods: Six candidate reference genes were analyzed in 33 paired tumor and non-tumor tissues from untreated HCC patients. The genes expression stabilities were assessed by geNorm and NormFinder. Results: C-terminal binding protein 1(CTBP1) was the most stable gene among the 6 candidate genes evaluated by both geNorm and NormFinder. The expression stability values were 0.08 for CTBP1 and UBC, 0.09 for HPRT1, 0.12 for HMBS, 0.14 for GAPDH and 0.18 for 18S with geNorm analysis. The stability values suggested by NormFinder software were CTBP1: 0.044, UBC: 0.063, HMBS: 0.072, HPRT1: 0.072, GAPDH: 0.098 and 18S rRNA: 0.161. Conclusion: This is the first systematic analysis which suggested CTBP1 as the highest expression-stable gene in human male HBV infection related-HCC with cirrhosis. We recommend CTBP1 as the best candidate reference gene when RT-qPCR was used to determine gene(s) expression in HCC. This may facilitate the relevant HBV related HCC studies in the future. Show more

Keywords: Hepatocellular carcinoma, hepatitis B virus, liver cirrhosis, male gender, C-terminal binding protein 1, reference gene, RT-qPCR

DOI: 10.3233/CBM-130365

Citation: Cancer Biomarkers, vol. 13, no. 5, pp. 345-349, 2013

Authors: Wang, Wenjie | Li, Huiyu | Zhou, Yan | Jie, Shenghua

Article Type: Research Article

Abstract: Background: Microvesicles (MVs) are produced through the outward vesicles budding and fission from the cell surface. Recently, it was discovered that extracellular MVs circulate in bodily fluids of cancer patients and could serve as potential diagnostic biomarkers. However, the diagnostic and prognostic roles of peripheral circulating MVs for hepatocellular carcinoma (HCC) remain unclear. Objective: The aim of this study was to investigate whether the peripheral blood MVs could serve as potential biomarkers for detection of HCC. Methods: Peripheral blood samples were obtained prior to treatment from 55 patients with HCC, 40 patients with liver cirrhosis and …21 healthy controls. MVs were isolated from peripheral blood by centrifugation and measured by using bicinchoninic acid assay. Results: Peripheral blood MVs levels were significantly elevated in HCC patients compared to those in liver cirrhosis (p< 0.001). Furthermore, MVs levels was correlated with the HCC tumor size, pathological classification and TNM stage (p< 0.01). Of note, MVs levels were significantly reduced in the 1 month post-operative blood samples when compared to those in the pre-operative samples in the 17 HCC cases tested. MVs levels did not relate to liver enzymes, AFP levels, alcohol drinking or smoking habits (p> 0.05). In contrast, serum MVs levels correlated with the age of patients, leukocytes, platelets and prothrombin time. The results of receiver operating characteristic (ROC) analysis indicated better performance of MVs than AFP for early detection of HCC. The areas under the ROC curve of MVs for discriminating patients with early (TNM stage I) and relatively early (TNM stage II) HCC from liver cirrhosis was 0.83 (95% CI: 0.74–0.93) and 0.94 (95% CI: 0.88–1.00), respectively. Conclusions: Peripheral blood MVs levels were increased in patients with HCC and associated with the progression of disease. Serum MVs might serve as novel biomarkers for the diagnosis of HCC at early stage. Show more

Keywords: HCC, MVs, AFP, diagnosis

DOI: 10.3233/CBM-130370

Citation: Cancer Biomarkers, vol. 13, no. 5, pp. 351-357, 2013

Authors: Kang, Melissa | Shen, Xiang J. | Kim, Sangmi | Araujo-Perez, Felix | Galanko, Joseph A. | Martin, Chris F. | Sandler, Robert S. | Keku, Temitope O.

Article Type: Research Article

Abstract: Background and Objective: African Americans have worse outcomes in colorectal cancer (CRC) than Caucasians. We sought to determine if KRAS, BRAF and PIK3CA mutations might contribute to the racial differences in CRC outcome. Methods: DNA was extracted from tissue microarrays made from CRC samples from 67 African Americans and 237 Caucasians. Mutations in KRAS, BRAF, and PIK3CA were evaluated by PCR sequencing. We also examined microsatellite instability (MSI) status. Associations of mutation status with tumor stage and grade were examined using a logistic regression model. Cox proportional hazards models were used to estimate the all-cause mortality associated with …mutational status, race and other clinicopathologic features. Results: KRAS mutations were more common in African Americans than among Caucasians (37% vs 21%, p=0.01) and were associated with advanced stage (unadjusted odds ratio (OR)=3.31, 95% confidence interval (CI) 1.03–10.61) and grade (unadjusted OR=5.60, 95% CI 1.01–31.95) among African Americans. Presence of BRAF mutations was also positively associated with advanced tumor stage (adjusted OR=3.99, 95%CI 1.43–11.12) and grade (adjusted OR=3.93, 95%CI 1.05–14.69). PIK3CA mutations showed a trend toward an association with an increased risk of death compared to absence of those mutations (adjusted for age, sex and CRC site HR=1.89, 95% CI 0.98–3.65). Among African Americans, the association was more evident (adjusted for age, sex and CRC site HR=3.92, 95% CI 1.03–14.93) and remained significant after adjustment for MSI-H status and combined education-income level, with HR of 12.22 (95%CI 1.32–121.38). Conclusions: Our results suggest that African Americans may have different frequencies of somatic genetic alterations that may partially explain the worse prognosis among African Americans with CRC compared to whites. Show more

Keywords: KRAS, BRAF, PIK3CA, colorectal cancer, African-Americans

DOI: 10.3233/CBM-130366

Citation: Cancer Biomarkers, vol. 13, no. 5, pp. 359-366, 2013

Authors: Su, Yanlin | Xiong, Jie | Bing, Zhitong | Zeng, Xiaomin | Zhang, Yong | Fu, Xiaohua | Peng, Xiaoning

Article Type: Research Article

Abstract: Background: Glioblastoma multiforme (GBM) remains the most common and aggressive primary brain tumor in adults with a poor median survival, and molecular biomarkers for GBM pathogenesis are in need. Purpose: The objective of this study is to identify potential novel genes for GBM pathogenesis by gene expression data mining. Materials and Methods: Available SAGE libraries of GBM, astrocytoma, and normal brain tissues were collected from the Cancer Genome Anatomy Project (CGAP). Significance analysis for microarray (SAM) and CGAP-SAGE-Genie-DGED were used to identify differentially expressed tags, and specific tags that were differentially expressed only in GBM were …further selected. Tags to genes association was performed by CGAP-SAGE-Genie-SAV. Immunohistochemistry was used to investigate distribution and validate expression of the interested gene. Results: Three genes were significantly differentially expressed just in brain. up-regulated expression of STAB1 and down-regulated expression of SH3GL2 and DNM3. Immunohistochemistry assay indicated that STAB1 mainly expressed in vascular endothelial cells and over-expressed in GBM samples compared to normal samples. Conclusions: Our study shows that data mining of public sources of gene expression is an effective way to identify novel tumor-associated genes, and this work may contribute to the identification of candidate genes for GBM angiogenesis. Show more

Keywords: GBM, astrocytoma, SAGE, specific gene, STAB1, angiogenesis

DOI: 10.3233/CBM-130367

Citation: Cancer Biomarkers, vol. 13, no. 5, pp. 367-375, 2013

Authors: Li, Wenjuan | Nichols, Krystle | Nathan, Cherie-Ann | Zhao, Yunfeng

Article Type: Research Article

Abstract: Background: Mitochondrial uncoupling protein 2 (UCP2) uncouples electron transport from ATP production. UCP2 has been shown to play an important role in obesity and diabetes. Interestingly, studies have demonstrated that UCP2 is up-regulated in human colon cancer samples. Objective: In order to study the role of UCP2 in human cancers, we detected the UCP2 protein level in various human tumor tissues. Methods: Six types of human tumor and adjacent normal tissue samples were collected and analyzed by Western blot assays to detect the levels of UCP2. Results: The results showed that in the human …head and neck, skin, prostate, and pancreatic tumor samples examined, the protein levels of UCP2 were significantly higher in tumor tissues than that in the adjacent normal tissues. The protein levels of UCP2 was lower in non-small cell lung tumor tissues, which is marginal significant. Conclusions: Over expression of UCP2 in certain tumors provides the rationale to speculate that UCP2 may promote tumor growth in these cancers. Show more

Keywords: Mitochondrial uncoupling 2, UCP2, oxidative phosphorylation, mitochondrial membrane potential

DOI: 10.3233/CBM-130369

Citation: Cancer Biomarkers, vol. 13, no. 5, pp. 377-383, 2013