Cancer Biomarkers - Volume 26, issue 3

Authors: Wu, Junxue | Zhang, Chao | Chen, Lu

Article Type: Research Article

Abstract: Osteosarcoma, a highly aggressive cancer, can rapidly metastasize to distant organs such as lung, liver, brain. Despite much progress in the therapeutic regime has been made, the prognosis of osteosarcoma remains poor. In present study, microRNA-511 (miR-511) is lowly expressed in osteosarcoma cells, including MG63, U-2 OS, Saos-2 cells, while mitogen activated protein kinase1 (MAPK1) is highly expressed in osteosarcoma cells. Interestingly, MAPK1 might be a target of miR-511. We found that overexpression of miR-511 by miR-511 mimic transfection may result to low expression of MAPK1. Further study showed that miR-511 mimic inhibits the development of osteosarcoma MG63 cell, including …proliferation and invasion. Moreover, miR-511 mimic transfection reduces metastatic osteosarcoma tumor burden in nude mice. These activities are mediated by targeting MAPK1. Our study provides a new sight for the molecular pathogenesis of osteosarcoma. Show more

Keywords: Osteosarcoma, MiR-511, proliferation, invasion, MAPK1

DOI: 10.3233/CBM-190534

Citation: Cancer Biomarkers, vol. 26, no. 3, pp. 343-351, 2019

Authors: Li, Zhichun | Guo, Qingbo | Lu, Yugang | Tian, Tian

Article Type: Research Article

Abstract: Aberrant expression of miR-181d has been noted in multiple human cancers, but its role in gastric cancer (GC) remains unclear. The aim of this study was to investigate the expression, clinical significance and functional role of miR-181d in GC. We applied quantitative real-time polymerase chain reaction (qRT-PCR) to quantify the expression of miR-181d in 131 GC tissues, as well as in GC cell lines. The correlation of miR-181d expression with overall survival of GC patients was analyzed using the Kaplan-Meier survival method. Cox regression analysis was conducted to further determine the prognostic value of miR-181d in GC. Cellular functional experiments …were carried out to calculate the effect that miR-181d had on GC behaviors. MiR-181d expression was significantly up-regulated in both GC tissues and cells (all P < 0.001), and correlated with TNM stage and lymph node metastasis (all P < 0.05). GC patients in the high miR-181d expression group had shorter survival time than those in the low miR-181d expression group (log-rank P < 0.001). Multivariate Cox regression analysis demonstrated that miR-181d expression and TNM stage were two independent prognostic markers for GC. Overexpression of miR-181d significantly promoted the NCI-N87 and MGC-803 cells proliferation, migration and invasion (all P < 0.05). MiR-181d serves a role as an oncogene in GC by promoting tumor progression. And miR-181d might be a novel predictive marker for the prognosis of GC patients. Show more

Keywords: MicroRNA-181d, prognosis, progression, gastric cancer

DOI: 10.3233/CBM-190091

Citation: Cancer Biomarkers, vol. 26, no. 3, pp. 353-360, 2019

Authors: Yue, Chen-Xi | Liu, Yu-Xi | Yun, Zhi-Yuan | Li, Na | Zhao, Chang-Jiu | Wang, Rui-Tao

Article Type: Research Article

Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor and second most common cause of tumor-related deaths worldwide. Activated platelets play a prominent role in tumor. Platelet distribution width (PDW) indicates platelets activation and is altered in malignancies. The aim of this study was to explore the prognostic value of PDW for overall survival (OS) in HCC patients. METHODS: We retrospectively reviewed 273 HCC patients at a single institution from 2010 to 2014. The relationship between PDW and clinicopathological characteristics was analyzed. Kaplan-Meier curves and multivariate Cox regression analyses were used to evaluate the …relationship of PDW with OS. RESULTS: Low PDW levels were observed in 127 (46.5%) out of 273 patients. A significant correlation was found between PDW and liver cirrhosis. Median follow-up was 36 months, survival curves revealed that the patients with increased PDW had significantly shorter survival time than those with normal PDW (p = 0.001). Cox regression analysis demonstrated that PDW was an independent prognostic factor for overall survival (hazard ratio, 2.464; 95% confidence interval [CI], 1.402–4.330, p = 0.001). CONCLUSION: PDW is significantly associated with OS in HCC. This result suggests activated platelet may affect clinical outcome and warrant continued investigation. Show more

Keywords: Hepatocellular carcinoma, platelet distribution width, prognosis

DOI: 10.3233/CBM-190474

Citation: Cancer Biomarkers, vol. 26, no. 3, pp. 361-366, 2019

Authors: Zhang, Junqiang | Sun, Gengyun | Mei, Xiaodong

Article Type: Research Article

Abstract: BACKGROUND: Family with sequence similarity 83 member A (FAM83A) can promote tumor cell proliferation and facilitate epidermal growth factor tyrosine kinase inhibitor resistance in some malignant tumors, but its role in lung cancer has not been directly explored. OBJECTIVE: We investigated FAM83A expression in lung adenocarcinoma (LUAD) and its significance in clinicopathologic characteristics and prognosis of the disease. PATIENTS AND METHODS: We analyzed the mRNA expression of FAM83A in LUAD and normal (or adjacent) lung tissues from Oncomine database firstly. Then, we detected FAM83A protein expression in five paired fresh LUAD and adjacent …lung tissue specimens from patients in our hospital by Western blotting. In addtion, FAM83A expression in 86 paraffin-embedded archived LUAD samples was evaluated by Immunohistochemistry, and the correlations between FAM83A expression and clinicopathologic characteristics and prognosis of the patients were analyzed. RESULTS: Oncomine data analysis manifested that FAM83A mRNA expression was increased in LUAD. Western blotting revealed higher FAM83A expression in fresh LUAD tissues than in the adjacent lung tissues (P = 0.036). Immunohistochemistry analysis on 86 paraffin samples further demonstrated that the LUAD tissue had higher FAM83A expression than adjacent lung tissue (P < 0.001). The correlation analysis revealed that advanced stage tumors (stage III–IV) had higher FAM83A expression than early stage tumors (stage I–II) (P = 0.004). High FAM83A expression was significantly associated with lymphnode involvement and clinical staging (P = 0.008 and 0.008 respectively). Univariate and multivariate Cox regression analysis manifested that FAM83A expression was an independent predictive factor for poor survival. Kaplan-Meier survival curves showed that patients with higher FAM83A expression had shorter overall survival than those with lower FAM83A expressions (P = 0.002). CONCLUSION: FAM83A is upregulated in advanced LUAD and is related to unfavorible prognosis. FAM83A might be a novel diagnostic and prognositic biomarker for LUAD. Show more

Keywords: Family with sequence similarity 83 member A (FAM83A), lung adenocarcinoma, prognositic

DOI: 10.3233/CBM-190520

Citation: Cancer Biomarkers, vol. 26, no. 3, pp. 367-373, 2019

Authors: Ni, Yanhong | Zhang, Xiaoxin | Wan, Yunxia | Dun Tang, Kai | Xiao, Yin | Jing, Yue | Song, Yuxian | Huang, Xiaofeng | Punyadeera, Chamindie | Hu, Qingang

Article Type: Research Article

Abstract: BACKGROUND: p16 has often been found to be overexpressed in patients oral squamous cell carcinoma (OSCC), but its prognostic value between anatomic subsites is still unclear. OBJECTIVE: The aim of this study was to investigate the diagnostic and prognostic values of p16 in OSCC originating from tongue, gingiva or buccal mucosa. METHODS: A total of 147 OSCC patients with tumors arising from the tongue, gingiva or buccal mucosa were enrolled in this study. p16 expression was detected using immunohistochemistry (IHC), and the presence of HPV16 was determined by real-time PCR in p16 positive …patients. The correlation of p16 expression with the clinical parameters was evaluated. RESULTS: Only one p16 positive patient with a cut off value of 25% and 75% was HPV16 positive. Although overall survival (OS), recurrence free survival (RFS) and metastasis free survival (MFS) had no significant differences between the p16 positive and negative patients, p16 negative patients (cut off value 25%) had more RFS in the buccal mucosa cancer (p = 0.03) than the p16-positive patients. CONCLUSIONS: The prevalence of HPV16 in Chinese OSCC patients was low. p16 overexpression decoupled from HPV infection was not a prognostic marker for OSCC patients except for patients with the buccal mucosa cancer. Show more

Keywords: HPV 16, p16 immunohistochemistry, oral squamous cell carcinoma, anatomical subsites

DOI: 10.3233/CBM-192402

Citation: Cancer Biomarkers, vol. 26, no. 3, pp. 375-383, 2019

Authors: Jing, Zhenhai | Gao, Lei | Wang, Hongzhou | Chen, Jing | Nie, Ben | Hong, Qing

Article Type: Research Article

Abstract: Accumulating evidence has shown that lncRNA GAS5 is a novel tumour-promoting RNA that contributes to tumour progression by sponging miRNAs. However, the detailed role of lncRNA GAS5 in B lymphocytic leukaemia is still unclear. A qRT-PCR assay was used to examine the levels of lncRNA GAS5 and miR-222 in leukomonocytes of patients with B lymphocytic leukaemia and in healthy donors. Raji cells were transfected with GAS5 overexpression or shRNA-GAS5 plasmids for 48 ⁢ h , and cell proliferation was assessed by the CCK-8 assay, while apoptosis and cell cycle progression were assessed using flow cytometry. The Transwell …assay was applied to detect the invasion of Raji cells with GAS5 overexpression or knockdown. The dual luciferase reporter assay and regression curve were conducted to evaluate the binding interaction between lncRNA GAS5 and miR-222. The results showed that the expression of lncRNA GAS5 was decreased in B lymphocytic leukaemia patients compared with the healthy group, and the levels of lncRNA GAS5 in B lymphocytic leukaemia cell lines were significantly higher than those in the normal B cell line, whereas the levels of miR-222 were increased in B lymphocytic leukaemia patients compared with the healthy group. Moreover, cell culture experiments indicated that lncRNA GAS5 overexpression decreased B lymphocytic leukaemia cell proliferation, promoted B lymphocytic leukaemia cell apoptosis, arrested B lymphocytic leukaemia cells in the G1 phase of the cell cycle, and inhibited B lymphocytic leukaemia cell invasion. Finally, the luciferase reporter assay showed a direct target interaction between lncRNA GAS5 and miR-222. The regression analysis showed a negative correlation between the levels of lncRNA GAS5 and miR-222. Thus, our data suggested that lncRNA GAS5 could effectively sponge miR-222 to modulate human B lymphocytic leukaemia cell tumourigenesis and metastasis. This work advances our understanding of the clinical significance of lncRNA GAS5 from the perspective of lncRNA-miRNA regulation. Show more

Keywords: B lymphocytic leukaemia, lncRNA GAS5/miR-222 axis, tumourigenesis and metastasis

DOI: 10.3233/cbm-190246

Citation: Cancer Biomarkers, vol. 26, no. 3, pp. 385-392, 2019