Cancer Biomarkers - Volume 13, issue 1

Authors: Zhao, Xiaomu | Bai, Zhigang | Wu, Ping | Zhang, Zhongtao

Article Type: Research Article

Abstract: Background: The effect of the protein S100P on biological characteristics of cancer is not clear, especially in gastric cancer. We previously showed that S100P positive gastric cancer patients have a better cumulative survival than S100P negative patients. Objective: To study the possible mechanisms of S100P enhanced the chemosensitivity to oxaliplatin in gastric cancer cell lines. Methods: S100P was overexpressed in vitro by plasmid transfection and downregulated by siRNA transfection in the BGC823 and SGC7901 gastric cancer cell lines. Cell survival rate, changes in the chemoresistance gene, such as GST-π, MDR1, MRP1, Topo-II, MVP and BCRP, intake …of anticancer drug were measured after oxaliplatin treatment. Results: In SGC7901 cells, MTT assay indicated that increased S100P expression levels decreased the survival rate and decreased S100P expression levels increased the survival rate. In BGC823 and SGC7901 cell lines, mRNA of MDR1, a chemoresistance genes, was decreased in cells that overexpressed S100P, and increased in cells with downregulation of S100P. Intracellular accumulation of platinum increased in cells with overexpressed S100P, and decreased in cells with S100P downregulation. Conclusions: S100P contributes to oxaliplatin chemosensitivity in gastric cell lines by increasing drug inflow. It might also be a novel independent prognostic factor in gastric cancer patients who receive adjuvant chemotherapy with oxaliplatin. Show more

Keywords: S100P, oxaliplatin, gastric cancer, chemosensitivity

DOI: 10.3233/CBM-130330

Citation: Cancer Biomarkers, vol. 13, no. 1, pp. 1-10, 2013

Authors: Dirican, Ahmet | Ekinci, Nese | Avci, Arzu | Akyol, Murat | Alacacioglu, Ahmet | Kucukzeybek, Yuksel | Somali, Isil | Erten, Cigdem | Demir, Lutfiye | Can, Alper | Bayoglu, Ibrahim Vedat | Koyuncu, Betul | Ulger, Eda | Tarhan, Mustafa Oktay

Article Type: Research Article

Abstract: Background: It is well known that tumor-infiltrating lymphocytes (TIL) and, to a lesser extent, peripheral hematologic parameters from patients with cancer have to effect on prognosis. The aim of this study was to evaluate the effect of hematologic parameters and TIL on prognosis of patients with gastric cancer. Methods: 236 patients who had diagnosed as gastric adenocarcinoma. All hematologic parameters were noted at the time of diagnosis. The number of lymphocyte aggregates as well as the number of lymphocytes within these agregat was counted.The prognostic significance and correlations of high neutrophil-lymphocyte ratio (NLR) together with TIL, was evaluated …by multivaried analysis. Results: The cut-off values of NLR and derived NLR (dNLR) were 3.8 and 2. The NLR was independently associated with survival (P< 0.001). dNLR was not independently associated with overall survival. No significant advantages for overall survival were found for the high TIL (p: 0.372). It was not determined correlation between TIL – NLR and TIL-lymphoid aggregate density (respectivly, P: 0.104; P: 0.246). Conclusions: The results suggest that the elevated NLR predicts poor overall survival following at the time diagnosis for all stage gastric cancer. dNLR was not independently associated with overall survival. There is insufficient evidence to the assesment of TIL by a nonspesific method. Therefore further studies is required, to confirm our hypothesis in larger patient cohorts. Show more

Keywords: Gastric cancer, neutrophil-lymphocyte ratio, prognosis, tumor-infiltrating lymphocytes

DOI: 10.3233/CBM-130331

Citation: Cancer Biomarkers, vol. 13, no. 1, pp. 11-20, 2013

Authors: Wang, Gang | Wang, Wenling | Zhou, Jianjiang | Yang, Xiaofeng

Article Type: Research Article

Abstract: Objective: To investigate the relationship between telomerase activity (TA) and matrix metallo proteinases 2 (MMP-2) on malignant behavior and prognosis predictable value in gastric cancer. Methods: Telomerase activity and MMP-2 protein expressions were tested in 40 gastric surgical resected cancer samples and the clinicopathological data of enrolled patients were obtained to get correlation analysis results. Results: The expression of telomerase was up-regulated with infiltrating depth, lymph node metastasis and stage (P< 0.01). Positive expression rate of MMP-2 in gastric cancer tissues was 44.35%, negative in normal gastric tissues. Multivariate analysis of Logistic regression showed telomerase activity …and MMP-2 expression were hazardous makers correlated with infiltrating depth (P< 0.05). Conclusion: Combined detections of telomerase activity and MMP2 protein could identify patients at high risk in disease recurrence and prognosis more efficiently. Show more

Keywords: Telomerase activity, MMP-2, gastric cancer, prognosis

DOI: 10.3233/CBM-130332

Citation: Cancer Biomarkers, vol. 13, no. 1, pp. 21-28, 2013

Authors: Zhong, Hong | Feng, Yi | Zheng, Gui-Xiong | Liang, Yan | Zhang, Jun-Yuan | Zheng, Bao-Shi | Feng, Xu

Article Type: Research Article

Abstract: Background: Results of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the adenocarcinomas of lung cancer are still debated. Objective: This meta-analysis was performed to evaluate the association between GSTP1 A/G gene polymorphism and the risk of adenocarcinomas of lung cancer. Methods: The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Results: 16 reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and the risk of adenocarcinomas of lung cancer. The G …allele and GG genotype were not associated with the susceptibility of risk of adenocarcinomas. Furthermore, in the sensitivity analysis, the results were similar with those from the non-sensitivity analysis. Conclusions: GSTP1 G allele or GG genotype is not a biomarker to be associated with the susceptibility of adenocarcinomas of lung cancer. Show more

Keywords: Lung cancer, adenocarcinomas, glutathione S-transferase P1, A/G gene polymorphism, meta-analysis

DOI: 10.3233/CBM-130322

Citation: Cancer Biomarkers, vol. 13, no. 1, pp. 29-35, 2013

Authors: Bai, Xiao-Yan | Lin, Jia-Ying | Zhang, Xu-Chao | Xie, Zhi | Yan, Hong-Hong | Chen, Zhi-Hong | Xu, Chong-Rui | An, She-Juan | Sheng, Gao-Ming | Wu, Yi-Long

Article Type: Research Article

Abstract: Background: The hedgehog (Hh) pathway is involved in embryogenesis and organogenesis. GLI3 is one of the zinc-finger transcription factors in the Hh signaling pathway, which exist in both full-length (GLI3FL) and truncated (GLI3TR) forms. We investigated GLI3 expression in patients with non-small cell lung cancer (NSCLC). The role of GLI3 in lung carcinogenesis and its correlation with clinicopathological factors and overall survival (OS) in patients with NSCLC were explored. Methods: GLI3FL and GLI3TR expression were analyzed immunohistochemically in 330 and 352 evaluable NSCLC tissues respectively. The association between GLI3FL and GLI3TR expression and clinicopathological parameters and OS were …statistically analyzed. Results: GLI3FL immunohistochemical staining could be observed in the cytoplasm, while GLI3TR staining could be observed in nucleus of malignant epithelial cells. High level expression of GLI3FL and GLI3TR were 52.7% and 45.2% respectively. GLI3FL was not significantly correlated with any clinicopathological parameter and survival. However, high-expression of GLI3TR was significantly associated with lymph node metastasis (P=0.013) and poor OS (28.4 vs. 40.8 months, P=0.010). In patients with adenocarcinoma of high and low GLI3TR expression, the median OS were 25.7 and 50.6 months respectively (P=0.004). Multivariate analysis showed that GLI3TR expression (P=0.036), tumor differentiation (P< 0.001), disease stage (P < 0.001) were independent prognostic factors for patients with NSCLC. Conclusion: Overexpression of GLI3TR in NSCLC, especially in adenocarcinoma, is associated with poor prognosis. GLI3TR expression is an independent prognostic factor in OS. GLI3TR may play an important role in the tumorigenesis of NSCLC. Show more

Keywords: Non-small cell lung carcinoma, prognosis, hedgehog signaling pathway, GLI3, immunohistochemisty

DOI: 10.3233/CBM-130312

Citation: Cancer Biomarkers, vol. 13, no. 1, pp. 37-47, 2013

Authors: Li, Jian | Bao, Qian-Lei | Wang, Yi | Hu, Yi-Ming | Chen, Ping

Article Type: Research Article

Abstract: Inactivation of the tumor suppressor genes and activation of oncogenes are involved in the development of cancer. The aim of this study was to evaluate the diagnostic value of the fragile histidine triad (FHIT) and p16 mRNA loss and the K-ras gene mutation in distinguishing malignant from benign pleural effusion. A total of 50 patients with malignant pleural effusion and 30 patients with benign pleural effusion were enrolled in this study. All pleural fluid specimens were evaluated in parallel by cytology, reverse transcriptase-PCR for the loss of FHIT and p16 mRNA, and PCR-SSCP (single-stranded conformation polymorphism) for the mutation of …K-ras gene. The detection rates of FHIT and p16 mRNA loss were significantly higher in malignant than in benign pleural effusion (P< 0.001 and P=0.001). The K-ras mutations were more frequent in malignant than benign pleural effusion (P=0.006). The sensitivity and specificity were 58% and 93% for FHIT loss, 48% and 90% for p16 loss, and 44% and 87% for the K-ras mutation, respectively. In combined evaluation with both FHIT and p16 loss, the sensitivity was 68%, and specificity was 90%. The combination of the three molecular markers reached 74% sensitivity, whereas the combined use of the cytology and the three markers increased the diagnostic yield of the former by 38%. More than one third of cytology negative malignant pleural effusion could be identified by at least one of the three markers. These results suggest that the detection of FHIT and p16 mRNA loss and the k-ras gene mutation in pleural fluid could be helpful adjunct to cytology in the diagnosis of malignant pleural effusion. Show more

Keywords: Pleural effusion, malignancy, diagnosis, FHIT, p16, K-ras

DOI: 10.3233/CBM-130319

Citation: Cancer Biomarkers, vol. 13, no. 1, pp. 49-58, 2013

Authors: Zhao, Yaodong | Xue, Yajun | Zhang, Quanbin | Wang, Ke | Yin, Jia | Lou, Meiqing

Article Type: Research Article

Abstract: Currently, the transcript abundance of key enzymes for chemotherapy drug metabolism, which may help in predicting the efficacy of a drug, can easily be detected in tumor tissues. However, there has been little research on the enzymes involved in the chemotherapy of gliomas. This study aimed to detect and compare the abundance of glioma chemotherapy drug-associated marker molecules in both gliomas and normal brain tissues and among gliomas of different grades. We examined the transcript abundance of four such marker molecules, MGMT, ERCC1, Topo IIα and Stathmin, in 46 glioma and 6 normal brain tissues. We also compared the abundance …of these molecules in normal brain tissues and glioma tissues with different malignancy grades. Furthermore, we described the variation of these molecules in different grades of gliomas by calculating the ratio of their maximum to their minimum. The transcript abundance of MGMT and ERCC1 was significantly higher in normal brain tissues than in glioma tissues. However, the opposite result was observed for Topo IIα. For Stathmin, no significant differences between normal brain tissues and gliomas tissues were found. For all 4 marker molecules, no significant differences were detected between grades of glioma. All four molecules exhibited wide variation in abundance, fluctuating significantly between gliomas. These results suggest that individualized detection and medication may be beneficial for treatment. Show more

Keywords: Transcript abundance, glioma, chemotherapy drugs, marker molecules

DOI: 10.3233/CBM-130320

Citation: Cancer Biomarkers, vol. 13, no. 1, pp. 59-66, 2013