Cancer Biomarkers - Volume 22, issue 3

Authors: Tao, Zhihang | Li, Stanley Xiangyu | Cui, Xiwei | Huang, Yamin | Zhu, Sha | Wang, Yexiao | Tan, Huixin | Ma, Xuelei

Article Type: Research Article

Abstract: BACKGROUND: Neutrophil-Lymphocyte Ratio (NLR) and Platelet-Lymphocyte Ratio (PLR) have been considered as indicators for prognosis in various cancers. However, the prognostic values of NLR and PLR have never been tested in gallbladder carcinoma (GBC) with hepatic involvement. OBJECTIVE: The aim of the current study was to assess the prognostic significance of NLR, PLR, and other candidate biomarkers in GBC with liver involvement. METHODS: Receiver operating characteristic (ROC) curve analyses were utilized to pinpoint the cut-off values for NLR, PLR, and Monocyte-Lymphocyte Ratio (MLR). Univariate analyses were employed to estimate the impact of NLR, …PLR, MLR, and other inflammatory indexes on median survival. Multivariate analyses were used to verify the independent prognostic predictors. RESULTS: Eighty four patients were enrolled from 2009 to 2017. The cut-off values for NLR, PLR, and MLR were 3.20, 117.75, and 0.25, respectively. Univariate analyses revealed that TNM stage, NLR, PLR, MLR, lactate dehydrogenase, alkaline phosphatase, and carcinoembryonic antigen were significantly associated with decreased survival in GBC with hepatic involvement. Advanced TNM stage (P < 0.001) and elevated preoperative NLR (P = 0.002) were significantly associated with lower median survival periods, as revealed by multivariate analyses. CONCLUSIONS: These findings suggest that preoperative NLR may be an independent prognostic factor in evaluating prognosis in GBC with liver involvement. Show more

Keywords: Gallbladder cancer, immunologic markers, overall survival, prognostic factors, serum markers

DOI: 10.3233/CBM-181230

Citation: Cancer Biomarkers, vol. 22, no. 3, pp. 551-557, 2018

Authors: Shen, Wenjie | Cui, Ming-Ming | Wang, Xin | Wang, Rui-Tao

Article Type: Research Article

Abstract: BACKGROUND: Esophageal cancer (EC) is the sixth most common cause of death from cancer. Altered mean platelet volume (MPV) levels were found in patients with malignancies. OBJECTIVE: The present study investigated whether MPV can predict the survival in EC patients. MEHTODS: The clinical data of 236 consecutive EC patients between January 2009 and December 2009 in our center were retrospectively analyzed. The overall survival rate was estimated using Kaplan-Meier method. Cox proportional hazards models were fitted to model the relationships between patient characteristics and prognosis. RESULTS: Decreased MPV was significantly …correlated with tumor location and tumor differentiation (p < 0.001). Moreover, survival analysis revealed that the overall survival of patients with MPV ⩽ 7.4 fL was significantly shorter than that of those with MPV > 7.4 fL. Multivariate analysis identified MPV as an independent poor prognostic factor for overall survival. CONCLUSIONS: Reduced MPV is associated with worse survival outcome in EC. Show more

Keywords: Esophageal cancer, mean platelet volume, prognosis

DOI: 10.3233/CBM-181231

Citation: Cancer Biomarkers, vol. 22, no. 3, pp. 559-563, 2018

Authors: Song, Rui | Zhang, Jia | Huang, Junhua | Hai, Tao

Article Type: Research Article

Abstract: OBJECTIVE: Breast cancer is a common malignancy in women and long non-coding RNAs (lncRNAs) have been shown to play key roles in the development and progression of breast cancer. In the present study, we examined the biological role of lncRNA gastric carcinoma highly expressed transcript 1 (GHET1) in breast cancer. METHODS: The expression of GHET1 was determined by qRT-PCR assay; CCK-8, colony formation, Transwell invasion and migration assays detected breast cancer cell proliferation, invasion and migration; cell apoptosis and cell cycle were determined by flow cytometry; protein levels were determined by western blot assay. …RESULTS: GHET1 was up-regulated in breast cancer tissues and cell lines, and the up-regulation of GHET1 was positively correlated with larger tumor size, advanced clinical stage, lymph node metastasis and shorter overall survival. Knockdown of GHET1 suppressed cell proliferation, invasion and migration, and induced apoptosis and G 0 /G 1 cell cycle arrest in MCF-cells. Knockdown of GHET1 also suppressed the protein levels of N-cadherin, vimentin, and decreased the protein level of E-cadherin in MCF-7 cells. On the other hand, overexpression of GHET1 promoted cell proliferation, invasion and migration, and inhibited cell apoptosis and increased cell population at S phase in BT-20 cells. Overexpression of GHET1 also promoted epithelial mesenchymal transition (EMT) in BT-20 cells. Furthermore, knockdown of GHET1 also suppressed in vivo tumor growth of MCF-7 cells, and also decreased the protein levels of N-cadherin and vimentin, and increased the protein levels of E-cadherin in the tumor tissues from the nude mice. CONCLUSIONS: Our results demonstrated that GHET1 was up-regulated in breast cancer tissues and cell lines, and promoted breast cancer cell proliferation, invasion and migration by affecting EMT. Our study for the first time revealed the biological functions of GHET1 in breast cancer. Show more

Keywords: Breast cancer, GHET1, cell proliferation, invasion and migration, apoptosis, epithelial mesenchymal transition

DOI: 10.3233/CBM-181250

Citation: Cancer Biomarkers, vol. 22, no. 3, pp. 565-573, 2018

Authors: Ma, De-Qiang | Zhang, Yin-Hua | Ding, De-Ping | Li, Juan | Chen, Lin-Li | Tian, You-You | Ao, Kang-Jian

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the impact of Bmi-1-mediated NF-κ B pathway on the biological characteristics of CD133 + liver cancer stem cells (LCSCs). METHODS: Flow cytometry was used to isolate CD133 + LCSC cells from Huh7, Hep3B, SK-hep1, and PLC/PRF-5 cells. CD133 + Huh7 cells were divided into Control, Blank, Bmi-1 siRNA, JSH-23 (NF-κ B pathway inhibitor), and Bmi-1 + JSH-23 groups. The properties of CD133 + Huh7 cells were detected by the colony-formation …and sphere-forming assays. Besides, Transwell assay was applied for the measurement of cell invasion and migration, immunofluorescence staining for the detection of NF-κ B p65 nuclear translocation, and qRT-PCR and Western blotting for the determination of SOX2, NANOG, OCT4, Bmi-1, and NF-κ B p65 expression. RESULTS: CD133 + Huh-7 cells were chosen as the experiment subjects after flow cytometry. Compared with CD133 - Huh-7 cells, the expression of CD133, OCT4, SOX2, NANOG, Bmi-1, and NF-κ B p65, the nuclear translocation of NF-κ B p65, the number of cell colonies and Sphere formation, as well as the abilities of invasion and migration were observed to be increased in CD133 + Huh-7 cells, which was inhibited after treated with Bmi-1 siRNA or JSH-23, meanwhile, the cell cycle was arrested at the G0/G1 and S phases with apparently enhanced cell apoptosis. Importantly, no significant differences in the biological characteristics of CD133 + Huh-7 cells were found between the Blank group and Bmi-1 + JSH-23 group. CONCLUSION: Down-regulating Bmi-1 may inhibit the biological properties of CD133 + LCSC by blocking NF-κ B signaling pathway, which lays a scientific foundation for the clinical treatment of liver cancer. Show more

Keywords: Liver cancer stem cells, Bmi-1, NF-κB pathway, CD133+

DOI: 10.3233/CBM-181329

Citation: Cancer Biomarkers, vol. 22, no. 3, pp. 575-585, 2018

Authors: Zahran, Asmaa M. | Mohammed Saleh, Mostafa F. | Sayed, Mona M. | Rayan, Amal | Ali, Arwa Mohammed | Hetta, Helal F.

Article Type: Research Article

Abstract: BACKGROUND: The bone marrow immunosuppressive microenvironment of AML patients sustains and modulates proliferation, survival and drug resistance of AML through deregulation of both innate and adaptive immune response. We aimed to investigate the level of Tregs, expression of Tim-3 on peripheral blood T cells, expression of CD200 in myeloid blasts in newly diagnosed AML patients with normal cytogenetics (AML-NC) and their prognostic impact. PATIENTS AND METHODS: This study included 40 patients with de novo AML-NC and 20 healthy controls. Flow-cytometry was used for detection of CD4+ CD25+ high FoxP3+ regulatory T …cells, Tim-3 expression on peripheral blood T cells and CD200 expression on myeloid blasts. RESULTS: The percentages of CD4+ CD25+ high and CD4+ CD25+ high Foxp3+ Tregs were significantly increased in AML patients than controls. The levels of Tregs, Tim-3/CD4 + , Tim-3/CD8 + , CD200 and MFI of CD200 were significantly lower in responding patients than in those with persistent leukemia. Only high CD200 expression (> 50%) showed statistically significant worse OS with P < 0.04. CONCLUSION: The increased levels of Tregs, Tim-3 expression on peripheral blood T cells and CD200 expression in myeloid blast in AML patients could play a role in the development of AML. Analysis of these markers could serve as prognostic markers and might guide the therapy in AML patients in the future. Show more

Keywords: Regulatory T cells, CD200, TIM3, acute myeloid leukemia, normal cytogenetics

DOI: 10.3233/CBM-181368

Citation: Cancer Biomarkers, vol. 22, no. 3, pp. 587-595, 2018