Cancer Biomarkers - Volume 11, issue 4

Authors: Wang, Yishan | Hu, Yanjie | Wang, Di | Yu, Kai | Wang, Ling | Zou, Yingchang | Zhao, Cong | Zhang, Xuanlang | Wang, Ping | Ying, Kejing

Article Type: Research Article

Abstract: Background: Volatile organic compounds (VOCs) biomarkers in breath provide a novel, noninvasive and quick approach to diagnosis lung cancer. The aim of the proposed study was to investigate the VOCs biomarkers in exhaled breath for lung cancer. Method: The VOCs in exhaled breath of 88 lung cancer patients, 70 lung benign disease and 85 healthy people were analyzed by Solid Phase Micro Extraction – Gas Chromatography Mass Spectrometry (SPME-GCMS). Three types of lung cancer cells and 18 lung cancer patients’ tissues were cultured in vitro. The VOCs in the headspace of these cultivations were analyzed as an evidence …of production mechanism of the VOCs in breath. Three lung cancer diagnosis models were constructed respectively in exhaled breath samples using Linear Discriminant Analysis (LDA). Leave one out cross validation was employed to evaluate these models. Results: 23 VOCs, whose areas under curve (AUC) of receiver operating characteristic (ROC) > 0.60 and p < 0.01, were confirmed as the VOCs biomarkers for lung cancer. Three diagnostic models based on 23 VOCs could easily discriminate lung cancer patients from controls with 96.47% sensitivity and 97.47% specificity. However, the discrimination between early stage and later stage lung cancer was not very obvious. Show more

Keywords: Lung cancer, biomarkers, exhaled breath, volatile organic compounds (VOCs)

DOI: 10.3233/CBM-2012-00270

Citation: Cancer Biomarkers, vol. 11, no. 4, pp. 129-137, 2012

Authors: Minamiya, Yoshihiro | Saito, Hajime | Ito, Manabu | Imai, Kazuhiro | Konno, Hayato | Takahashi, Naoko | Motoyama, Satoru | Ogawa, Jun-ichi

Article Type: Research Article

Abstract: Zinc Finger Homeobox 3 (ZFHX3) was first identified as a suppressor of alpha-fetoprotein gene and is a good candidate for the 16q22 tumor suppressor. In this study we investigated the relationship between tumoral ZFHX3 mRNA expression and the clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). We used semi-quantitative real time reverse transcription polymerase chain reaction to assess expression of ZFHX3 mRNA in tumor samples from 140 patients with NSCLC. We found that the 5-year overall survival rate among patients weakly expressing ZFHX3 was significantly poorer than among those expressing higher levels of ZFHX3 (P< 0.0001 by log-rank …test). Multivariate logistic regression analysis revealed being lower ZFHX3 expression are independent predictors of lymph node metastasis. With low-ZFHX3 tumors, there was a significantly (P=0.009) greater (7.39-fold higher) risk of lymph node metastasis. Multivariate Cox proportional hazard analyses revealed that being lower ZFHX3 expression (Hazard ratio, 4.42; 95% CI, 2.09–8.92; p=0.0002) were independent factors affecting 5-year overall survival. Ratio of ZFHX3 mRNA in tumor against normal lung in low-ZFHX3 tumor was lower than in high-ZFHX3 tumor. In conclusion, suppression of ZFHX3 expression in tumor cells decreases the survival rate among patients with NSCLC. Show more

Keywords: Prognosis, non-small cell lung cancer, Zinc Finger Homeobox 3, AT motif-binding factor 1, RT-PCR, alpha-fetoprotein

DOI: 10.3233/CBM-2012-00272

Citation: Cancer Biomarkers, vol. 11, no. 4, pp. 139-146, 2012

Authors: Xu, Qian | Xue, Fengxia | Yuan, Bibo | Zhang, Linqin | Li, Jie | He, Zhaofang

Article Type: Research Article

Abstract: Aim: To explore the possible association between the receptor for advanced glycation end products (RAGE) gene polymorphisms and the risk of cervical cancer. Method: We enrolled 488 patients with cervical squamous cell carcinoma and 715 age-matched female healthy subjects as controls. Human Papillomavirus (HPV) infection and four RAGE gene polymorphisms (–429T>C, –374T>A, 1704G>T, and 82G>S) in all subjects were determined. Results: The genotype distributions and allele frequencies of –429T>C, 1704 T>G and -374T>A were not significantly different between cervical cancer patients and controls (all P> 0.05). For 82G>S polymorphisms, the genotype distributions and allele frequencies were …significantly different between the two groups. The cervical cancer patients had markedly higher percentage of 82SS carriage than controls. The logistic regression analysis showed that the 82SS genotype was associated with significantly elevated risk for cervical cancer, adjusted odds ratio (OR) was 1.98, (P< 0.001). In addition, the 82SS carriers had significantly lower serum soluble RAGE (sRAGE) levels than 82GS and 82GG. The polymorphisms of –429T>C, –374T>A and 1704T>G did not affect the cervical cancer risk and the serum sRAGE levels. When all the cancer patients were stratified by HPV infection status, the 82GS and 82SS genotype carriers in the HPV infection subgroup had increased risk for cervical cancer versus 82GG (OR=1.68 and 1.74, respectively, both P<0.05). This trend was not observed in the subgroup with no detectable HPV DNA. Conclusion: Our results suggest that the RAGE 82G>S polymorphisms, interacting with HPV infection, are implicated in the occurrence of cervical cancer. Show more

Keywords: Polymorphisms, cervical cancer, risk, the receptor for advanced glycation end products

DOI: 10.3233/CBM-2012-00277

Citation: Cancer Biomarkers, vol. 11, no. 4, pp. 147-153, 2012

Authors: Khanra, Kalyani | Panda, Kakali | Bhattacharya, Chandan | Mitra, AK | Sarkar, Ranu | Banerjee, Sipra | Bhattacharyya, Nandan

Article Type: Research Article

Abstract: Background: Base excision repair (BER) is a key pathway for maintaining genomic stability. A key enzyme in the BER pathway is DNA polymerase beta (polβ), which removes the deoxyribose phosphate group (dRP) and fills in the gap with a nucleotide after the DNA lesion is excised. It has been shown that more than thirty percent of breast, bladder, esophageal, colon, and gastric cancer samples studied so far have exhibited DNA polymerase beta mutation. Aim: To examine the association between polβ polymorphism and ovarian cancer, case control study was performed using one hundred fifty two cancer samples and non-metastatic …normal samples from the same patients in Indian population. Design: The polβ polymorphism was studied in ovarian carcinoma tissues samples initially by RT-PCR followed by sequencing and then by western blot analysis. Result: A new type of variant was detected along with the WT allele (polβ Δ 208 − 304 ). Stage IV samples have shown a significant factor for cancer progression in ovarian cancer patients of India [OR=3.58; 95% CI (1.6–7.9); and p=0.001]. The association study involving serous type and the variant showed a tendency towards ovarian carcinogenesis [OR=1.57; 95% CI (0.8–3.1); p=0.19]. The western blot analysis result indicates that the specific deletion appears to be associated with disease progression. Conclusion: The result reveals that this variant form of polβ is a predisposing factor for stage IV ovarian cancer samples in Indian population. Show more

Keywords: DNA polymerase β, polymorphism, ovarian cancer, India

DOI: 10.3233/CBM-2012-00275

Citation: Cancer Biomarkers, vol. 11, no. 4, pp. 155-160, 2012

Authors: Liang, Hongyan | Block, Timothy M. | Wang, Mengjun | Nefsky, Bradley | Long, Ronald | Hafner, Julie | Mehta, Anand S. | Marrero, Jorge | Gish, Robert | Norton, Pamela A.

Article Type: Research Article

Abstract: The Golgi phosphoprotein GP73 is elevated in the circulation of individuals with a diagnosis of hepatocellular carcinoma. Its usefulness as a biomarker of HCC is questioned, since it has also been reported to be elevated in the circulation of people with liver cirrhosis. Regulation of GP73 by inflammatory cytokines is therefore of interest. The interleukin-6 (IL-6) family cytokines were tested for effects on GP73 mRNA and/or protein levels in human hepatoblastoma HepG2 cells. Levels of GP73 mRNA and protein were up-regulated in HepG2 cells following treatment with either proinflammatory cytokine IL-6 or the related cytokine oncostatin M (OSM). Induction required …the shared receptor subunit gp130, and correlated with increased tyrosine phosphorylation of STAT3. Maximal cytokine-mediated induction was not observed in the presence of protein synthesis inhibitor cycloheximide, suggesting additional regulatory factors play an important role. ELISA measurement of GP73 and IL-6 levels in the sera of patients with pre-malignant liver disease revealed a significant correlation between circulating levels of the two proteins. Similarly, a sensitive ELISA assay was developed to measure circulating OSM. OSM levels were elevated 6–7 fold in sera from patients with either cirrhosis or HCC relative to controls without liver disease. Although there was an association between levels of GP73 and OSM in serum from people with liver cirrhosis, there was not a statistically significant correlation in HCC, suggesting that the role of the cytokines in determining circulating levels may be complex. To our knowledge, this is the first report of OSM elevation being associated with liver disease. Show more

Keywords: Golgi phosphoprotein, GOLPH2, GOLM1, cirrhosis

DOI: 10.3233/CBM-2012-00276

Citation: Cancer Biomarkers, vol. 11, no. 4, pp. 161-171, 2012

Authors: Birgisson, Helgi | Jirström, Karin | Stenman, Ulf-Håkan

Article Type: Research Article

Abstract: Increased serum concentrations of the β subunit of human chorionic gonadotropin (hCGβ) are associated with adverse prognosis in several cancers. The aim of the present study was to analyse the association between serum hCGβ recurrence, and survival, in patients with colorectal cancer. The concentrations of hCGβ were determined in serum collected preoperatively from 324 patients with colorectal cancer, of whom 270 were curatively treated. The serum concentrations of hCGβ were associated with increasing age and they were higher in women than in men. Using the 75th percentile (1.55 pmol/L) as a cut-off for serum hCGβ, overall survival (OS) was shorter …in patients with elevated concentrations (HR 1.95; 95% CI 1.39–2.74; P=0.004), and this association was stronger in women (P=0.022) than in men (P=0.061). In multivariate analyses including age, disease stage, tumour differentiation, vascular invasion and CEA, high serum hCGβ concentrations remained an independent prognostic factor for adverse OS in women (HR 2.26; 95%CI 1.39–3.67), but not in men (HR 0.78; 95%CI 0.41–1.51). The same trend was observed for disease free- and cancer specific survival. High serum concentration of hCGβ is an independent prognostic factor for adverse outcome in women with colorectal cancer. Show more

Keywords: Cancer, colorectal, human chorionic gonadotropin beta, hCG, prognosis, survival

DOI: 10.3233/CBM-2012-00279

Citation: Cancer Biomarkers, vol. 11, no. 4, pp. 173-181, 2012