Cancer Biomarkers - Volume 24, issue 1

Authors: Huang, Chaoping | Li, Yan | Zhao, Wei | Zhang, Aobo | Lu, Cheng | Wang, Zhenxiao | Liu, Liangfa

Article Type: Research Article

Abstract: Cancer stem cells (CSCs) have the ability to dictate tumor initiation, recurrence, and metastasis. Here, we examined the expression of aα 2δ 1 + in laryngeal cancer tissues and further determined the effect of α 2δ 1 on the migratory ability and tumorigenicity of laryngeal cancer cells. Immunofluorescence staining revealed that α 2δ 1 was positive in 13 (13/16, 81.25%) cases in laryngeal squamous cell carcinoma (LSCC) tissues, 7 (7/16, 43.75%) cases in paracancerous tissues and only 2 (2/16, 12.5%) cases in normal tumor …tissues. Our quantitative RT-PCR assays further showed that α 2δ 1 + LSCC cells expressed significantly higher levels of stem cell-associated genes and drug efflux and resistance genes versus α 2δ 1 - cells. Sphere-forming assays demonstrated higher sphere-forming efficiency in the α 2δ 1 + versus α 2δ 1 - subpopulation. Our Matrigel assays showed that α 2δ 1 + cells exhibited significantly greater invasive and migratory ability than α 2δ 1 - cells. Furthermore, the percentage of purified α 2δ 1 + in TU686 and TU212 cells treated cisplatin or paclitaxel was significantly higher than that of the control group. Tumor xenograft assays revealed that the tumorigenicity of α 2δ 1 + cells was much higher than α 2δ 1 - cells. In conclusion, a α 2δ 1 + subpopulation with CSC-like property was present in laryngeal cancer and possessed high self-renewal activity and was sufficient for tumor growth, differentiation, migration, invasion, and chemotherapeutic resistance. They could represent a promising therapeutic target for LSCC. Show more

Keywords: Laryngeal squamous cell carcinoma, cancer stem cells, α2δ1

DOI: 10.3233/CBM-181947

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 97-107, 2019

Authors: Luo, Junfeng | Lou, Zhengda | Zheng, Junzheng

Article Type: Research Article

Abstract: Bladder cancer is frequently occurred in urinary system and has complicated pathogenesis factors including both genetics and environmental factors that have not been fully illustrated. Hypoxia can further induce tumor progression. ROCK2 has abnormal expression in various tumors but its expression or functional role in bladder cancer have not been illustrated. In vitro cultured bladder cancer cell line T24 was randomly assigned into control group, hypoxia group (prepared under hypoxic culture), and ROCK2 siRNA group (transfected with ROCK2 siRNA after hypoxia treatment). Real-time PCR and Western bot measured ROCK2 expression. MTT assay tested cell proliferation, and cell migration was …quantified. Cell apoptosis was measured by caspase3 activity assay kit and Transwell chamber measured cell migration. Western blot quantified expressional change of HIF-1α and E-cadherin, and Wnt signal pathway proteins including Wnt4, and β -catenin. ROCK2 is up-regulated in bladder cancer T24 cells under hypoxia, and can facilitate cell proliferation, migration and invasion, inhibited Caspase3 activity, enhanced HIF-1α expression, decreased E-cadherin expression, and up-regulated Wnt4 and β -catenin (p < 0.05 comparing to hypoxia group). Under hypoxia conditions, ROCK2 can facilitate apoptosis of bladder cancer cells via modulating Wnt signal pathway, inhibit cell proliferation, migration, invasion or formation of epithelial mesenchymal transition (EMT). Show more

Keywords: ROCK2, bladder cancer, Wnt signal pathway, hypoxia, HIF-1α, cell proliferation

DOI: 10.3233/CBM-181949

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 109-116, 2019

Authors: Moschovis, D. | Vasilaki, E. | Tzouvala, M. | Karamanolis, G. | Katifelis, H. | Legaki, E. | Vezakis, A. | Aravantinos, G. | Gazouli, M.

Article Type: Research Article

Abstract: BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging as candidate biomarkers of cancer, having regulatory functions in both oncogenic and tumor-suppressive pathways. Concerning pancreatic cancer (PC), deregulation of lncRNAs involved in tumor initiation, invasion, and metastasis seem to play a key role. However, data is scarce about regulatory mechanism of lncRNA expression. OBJECTIVE: The aim of our study was to investigate the contribution of two lncRNAs polymorphisms (rs1561927 and rs4759313 of PVT1 and HOTAIR, respectively) in PC susceptibility. METHODS: A case-control study was conducted analysing rs1561927 and rs4759313 polymorphisms using DNA collected in a …population-based case-control study of pancreatic cancer (111 pancreatic ductal adenocarcinoma cases (PDAC), 56 pancreatic neuroendocrine tumor (PNET), and 125 healthy controls). RESULTS: Regarding the PVT1 rs1561927 polymorphism the G allele was significantly overrepresented in both PDAC and PNET patients compared to the controls, while the presence of the HOTAIR rs4759314 G allele was found to be overrepresented in the PNET patients only compared to the controls. The PVT1 rs1561927 AG/GG genotypes were associated with poor overall survival in PDAC patients. CONCLUSIONS: Our results suggested that polymorphisms of these two lncRNA polymorphisms implicated in pancreatic carcinogenesis. Further large-scale and functional studies are needed to confirm our results. Show more

Keywords: Long non-coding RNA, polymorphisms, pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumors

DOI: 10.3233/CBM-181959

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 117-123, 2019

Authors: Su, Hailong | Wang, Xuebo | Song, Jingjing | Wang, Yongjiao | Zhao, Yingchun | Meng, Juan

Article Type: Research Article

Abstract: BACKGROUND: Previous studies demonstrated that miR-539 play an important role in the carcinogenesis of some cancers. The aim of the present study was to determine the role of miR-539 in the pathogenesis of Wilms’ Tumor (WT). METHODS: The expression level of miR-539 was measured by qRT-PCR in 42 WT tissues and SK-NEP-1 cell line. Protein expression of genes (E-cadherin, N-cadherin, Vimentin, Notch 1, Notch 3 and JAG1) was assessed by Western blot. The function of miR-539 was investigated in SK-NEP-1 cells by MTT and Transwell assays. The relationship between miR-539 and JAG1 was verified by a …dual luciferase assay in SK-NEP-1 cells. RESULTS: The expression level of miR-539 was significantly decreased in WT tissues. Downregulation of miR-539 was closely related to NWTS-5 stage, lymph node metastasis and histological type of WT patients. Furthermore, low miR-539 expression was associated with a shorter overall survival rate in WT patients. In vitro , overexpression of miR-539 suppressed proliferation, migration and invasion of SK-NEP-1 cells. In addition, JAG1 was a direct target of miR-539. MiR-539 inhibited the development of WT by inhibiting JAG1-Notch1/3 expressing and blocking EMT. CONCLUSION: MiR-539 inhibited the progression of WT through downregulation of JAG1 and Notch1/3. Show more

Keywords: Wilms Tumor, miR-539, JAG1, Notch 1, Notch 3

DOI: 10.3233/CBM-181972

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 125-133, 2019

Authors: Surov, Alexey | Meyer, Hans Jonas | Höhn, Anne-Kathrin | Schob, Stefan | Winter, Karsten | Sabri, Osama | Purz, Sandra

Article Type: Research Article

Abstract: BACKGROUND: The aim of our study was to investigate possible relationships between 18 F-FDG-PET parameters and clinically relevant histopathological findings in patients with cervical cancer (CC). METHODS: Eighteen female patients (mean age 55.4 years) with histologically confirmed squamous cell CC were involved into the study. In all cases, 18 F-FDG-PET CT was performed. Mean and maximum standardized uptake values (SUV mean and SUV max ), total lesion glycolysis (TLG) and metabolic tumor volume (MTV) were determined on PET-images. For every tumor …the following specimen stainings were performed: epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, hypoxia-inducible factor (HIF)-1α , and histone 3. All stained specimens were digitalized and analyzed by using the ImageJ software 1.48v. Spearman’s correlation coefficient (p ) was used to analyze associations between investigated parameters. p -values < 0.05 were taken to indicate statistical significance. RESULTS: TLG and MTV correlated well with expression of EGFR (p = 0.601, P = 0.008 and p = 0.586, P = 0.011, respectively). SUV median correlated inversely with expression of HIF 1alpha (p = - 0.509, P = 0.031). SUV mean tended to correlate with expression of EGFR and HIF 1alpha. None of the PET parameters correlated with expression of Histone 3, p53 and VEGF. CONCLUSION: TLG and MTV can reflect expression of EGFR and SUV median correlated significantly with expression of HIF-1α . None of the PET parameters can predict expression of Histone 3, p53 and VEGF. Show more

Keywords: Uterine cervical cancer, 18F-FDG-PET, EGFR, VEGF, p53, HIF 1alpha, p53

DOI: 10.3233/CBM-182019

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 135-140, 2019