Cancer Biomarkers - Volume 23, issue 2

Authors: Wu, Jiali | Xiang, Zheyi | Bai, Le | He, Lagu | Tan, Li | Hu, Min | Ren, Yaping

Article Type: Research Article

Abstract: BACKGROUND: It is reported that prothrombin induced by vitamin K absence-II (PIVKA-II) has a better performance of diagnosis for HCC, and has also been known to be an independent risk factor for vascular invasion. Few studies study the relationship between PIVKA-II and HBV DNA. OBJECTIVE: To determine the clinical value of serum Prothrombin induced by vitamin K absence-II (PIVKA-II) in early hepatocellular carcinoma (HCC), and to explore its relationship with vascular invasion and HBV DNA. METHODS: In a Chinese cohort, we conducted a case-control study to compare the performances of a-fetoprotein (AFP) and …PIVKA-II serum levels for diagnosis of HCC and early HCC. Fifty one healthy controls, 37 chronic hepatitis patients, 43 cirrhotic patients and 143 HCC cases of which 48 (33.57%) had early stage HCC (n = 19 very early, n = 29 early) were enrolled. We explored the correlation between PIVKA-II serum level and several pathological features such as vascular invasion. The serum levels of and AFP were measured by chemiluminescence assay (CLIA) and electrochemiluminescence assay (ECLA). RESULTS: The serum levels of both PIVKA-II and AFP in HCC group were higher than that in chronic hepatitis, cirrhosis and healthy control groups. The sensitivity, specificity, positive predictive value, negative predictive value and kappa of PIVKA-II were higher than AFP in the diagnosis of HCC. Serum PIVKA-II level was correlated with tumor size, tumor cell differentiation and BCLC staging (P < 0.05). For the diagnosis of early HCC, the combination of PIVKA-II (AUC 0.812; 95% CI, 0.702–0.894) and AFP (0.797; 95% CI, 0.686–0.883) slightly improve the diagnostic performance for early HCC(AUC 0.849; 95% CI, 0.745–0.923). PIVKA-II > 166 mAU/ml is an independent risk factor for vascular invasion. The serum HBV DNA level in cirrhosis and HCC patients was significantly higher than in chronic hepatitis patients. We detected a negative association between serum PIVKA-II and serum HBV DNA levels. CONCLUSIONS: PIVKA-II was more efficient than AFP for the diagnosis of early HCC and has no correlation with serum HBV DNA levels. Show more

Keywords: Hepatocellular carcinoma, prothrombin induced by vitamin K absence-II, alpha fetoprotein, HBV DNA load, vascular invasion

DOI: 10.3233/CBM-181402

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 235-242, 2018

Authors: Zhang, Wei-Yi | Liu, Yin-Jiao | He, Yan | Chen, Ping

Article Type: Research Article

Abstract: OBJECTIVES: Cervical cancer (CC) is a common malignant tumor in the female reproductive system that is characterized by a high metastatic potential. LncRNA ANRIL has been found to be a cancer oncogene in multiple tumors. In our study, we altered the expression of ANRIL in CC cells and evaluated its ability on influencing proliferation, migration and invasion of CC cells and associated mechanism. METHODS: Differentially expressed lncRNAs in CC were identified by microarray and TCGA analyses. CC tissues and adjacent tissues were collected in order to extract CC cells. The expression of ANRIL was determined by …RT-qPCR. The CC cells were transfected with siRNA or si-NC against ANRIL to find out whether ANRIL can influence the expression of Cyclin D1, CDK4, CDK6, E-cadherin, vimentin and N-cadherin, as well as affect cell proliferation, cell apoptosis, cell migration and cell invasion of CC cells. RESULTS: Based on TCGA and microarray analyses, ANRIL was predicted to be highly expressed in CC and CC with migration. Then further verification was obtained by means of RT-qPCR that ANRIL was highly expressed in CC tissues. In addition, high expression of ANRIL was related to increased E-cadherin expression, high migration of CC as well as decreased cell apoptosis rate. On the other hand, inhibition of ANRIL expression led to decreased expressions of Cyclin D1, CDK4, CDK6, N-cadherin and Vimentin, along with attenuated cell proliferation, migration and invasion of CC cells. CONCLUSION: The key findings of our study demonstrated that the inhibition of lncRNA ANRIL reduces the proliferation, migration and invasion capabilities of CC cells. Down-regulation of ANRIL may serve as a potential therapeutic target in the treatment of CC. Show more

Keywords: Long non-coding RNA ANRIL, cervical cancer, proliferation, migration, invasion

DOI: 10.3233/CBM-181467

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 243-253, 2018

Authors: Wang, Xinyang | Zhao, Xinshu | Chou, Jing | Yu, Jiaying | Yang, Tongshu | Liu, Liyan | Zhang, Fengmin

Article Type: Research Article

Abstract: BACKGROUND: This study investigated the use of serum amino acids and organic acids profiles as the novel metabolites for screening breast cancer (BC) patients. METHODS: A total of 116 subjects as training set were divided into the following three groups: BC patients (n = 34), benign (BE) patients (n = 38) and controls (n = 44). The amino acids profiles from three groups were measured using liquid chromatography-mass spectrometry and organic acids profiles in three groups were studied by gas chromatography-mass spectrometry. …The resultant study data set was subjected to multivariate statistical analysis to identify important metabolites related with BC and construct the criteria for discriminating BC patients from BE subjects or controls. A test data set derived from 60 patients (30 BC and 30 BE subjects) and 30 controls was used to validate the stability of the different metabolites. RESULTS: The serum amino acids and organic acids profiles significantly differed between the BC patients, BE patients and the controls. Our results demonstrate that combinations of three candidate metabolites from taurine, glutamic acid and ethylmalonic acid were found to mirror tumour burden, with AUC values ranging from 0.751 to 0.834 when comparing BC patients to the controls. The areas under the curve from the taurine, glutamic acid and ethylmalonic acid in validated study were 0.901, 0.924 and 0.749, respectively. CONCLUSIONS: This study shows that amino acids and organic acids profiles will be a potential screening tool for BC patients. The dysregulated metabolism of amino acids and organic acids in breast cancer might be useful for the diagnosis, therapy, prognosis and understanding the pathogenesis of breast cancer. Show more

Keywords: Breast cancer, metabolomics, amino acids profiles, organic acids profiles, serum

DOI: 10.3233/CBM-181500

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 255-268, 2018

Authors: Liu, Yuhan | Zhang, Juan | Xing, Cuihong | Wei, Shuxin | Guo, Na | Wang, Yanli

Article Type: Research Article

Abstract: OBJECTIVE: Osteosarcoma is the most common malignant tumor of bone with high recurrent rate. miR-486 was downregulated and acted as a tumor suppressor in plenty of tumors. The purpose of this study was to explore how miR-486 worked in osteosarcoma on cell invasion and EMT. RESULTS: miR-486 was low expressed in osteosarcoma while PIM1 was overexpressed, and it had negative correlation between miR-486 and PIM1. miR-486 upregulation or PIM1 downregulation could inhibit osteosarcoma cell invasion and EMT. Meanwhile, miR-486 mediated PIM1 expression through binding to PIM1 mRNA 3’-UTR. PIM1 could reveal partial function of miR-486 on …osteosarcoma invasion. In addition, miR-486 low expression or PIM1 overexpression predicted poor prognosis of osteosarcoma patients. CONCLUSION: miR-486 regulated osteosarcoma cell invasion and EMT through targeting to PIM1. miR-486 low expression or PIM1 overexpression predicted poor prognosis of osteosarcoma patients. The newly identified miR-486/PIM1 axis provides novel insight into the pathogenesis of osteosarcoma. Show more

Keywords: miR-486, PIM1, invasion, EMT, osteosarcoma

DOI: 10.3233/CBM-181527

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 269-277, 2018

Authors: Liu, Jianmin | Liu, Beibei | Guo, Yuanyuan | Chen, Zhijun | Sun, Wei | Gao, Wuyue | Wu, Hongliang | Wang, Yan

Article Type: Research Article

Abstract: BACKGROUND: Clear cell renal cell carcinoma (CCRCC) is the most aggressive form of renal cell carcinoma (RCC). OBJECTIVE: This study was aimed to identify the differentially expressed miRNAs and target genes in CCRCC. METHODS: The miRNA and mRNA next-generation sequencing data were downloaded from The Cancer Genome Atlas (TCGA) dataset. Differential expression analysis was performed, followed by correlation analysis of miRNA-mRNA. Functional enrichment and survival analysis was also performed. RESULTS: Seven hundred and eighty-seven patients with CCRCC from TCGA data portal were included in this study. A total of 52 …differentially expressed miRNAs were identified in CCRCC. Then 2361 differentially expressed genes (DEGs) were identified. Prediction analysis and correlation analysis revealed that 89 miRNA-mRNA pairs were not only predicted by algorithms but also had a significant inverse relationship. Several differentially expressed miRNAs such as hsa-mir-501 and their target genes including AK1, SLC25A15 and PCDHGC3 had a significant prognostic value for CCRCC patients. CONCLUSIONS: Alterations of differentially expressed miRNAs and target genes may be involved in the development of CCRCC and can be considered as the prognostic markers for CCRCC. Show more

Keywords: Clear cell renal cell carcinoma, differentially expressed miRNAs, targets, survivability

DOI: 10.3233/CBM-181558

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 279-290, 2018

Authors: Tian, Yuan | Zhao, Ke | Yuan, Luer | Li, Jialing | Feng, Shuangbing | Feng, Yufeng | Fang, Zhongqi | Li, Hui | Deng, Ruoyu

Article Type: Research Article

Abstract: BACKGROUND: Although up-regulation of EIF3B correlates with poor prognosis in carcinomas, the role of EIF3B in non-small cell lung cancer (NSCLC) is rarely known. OBJECTIVE: We aimed to investigate correlation of EIF3B with clinicopathological features and prognosis in NSCLC patients, and clarify its effect on cells proliferation and apoptosis. METHODS: Two hundred and eleven NSCLC patients underwent surgery were retrospectively reviewed. Tumor tissue and paired adjacent tissue were obtained. EIF3B expression was detected by immunohistochemistry, qPCR and western blot. EIF3B inhibitor, blank inhibitor, blank mimic and EIF3B mimic plasmids were transfected to A-549 …cells. Cells proliferation and apoptosis were measured by CCK-8 and AV/PI. All processes were repeated for validation in PC9 cells. RESULTS: EIF3B expression increased in tumor tissue compared to paired adjacent tissue, and positively correlated with tumor size, lymph node metastasis and TNM stage. K-M curves revealed patients with EIF3B high expression had shorter DFS and OS, and its high expression independently predicted unfavorable DFS and OS. In vitro , EIF3B expression increased in NSCLC cells compared to normal cells. EIF3B increased cells proliferation but inhibited cells apoptosis. CONCLUSIONS: EIF3B overexpression correlates with advanced disease conditions and poor prognosis, and it promotes cells proliferation while inhibits apoptosis in NSCLC. Show more

Keywords: EIF3B, NSCLC, clinicopathological features, prognosis, proliferation, apoptosis

DOI: 10.3233/CBM-181628

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 291-300, 2018

Authors: Zhu, Lin | Chen, Yinan | Nie, Kai | Xiao, Yongxin | Yu, Hong

Article Type: Research Article

Abstract: MiRNAs regulated most genes expression, which were proved important in various tumors. In this study, we want to investigate miR-101 effect and molecular mechanism on pancreatic cancer (PC), the research about this was blank now. RT-PCR analysis showed that miR-101 expression was declined in PC. MTT assay found that miR-101 mimic suppressed cell viability, while suppressing miR-101 facilitated cell proliferation. Transwell assay showed that miR-101 mimic inhibited cell invasion, but promoted cell invasion by miR-101 inhibitor. With TargetScanHuman’s help, we verified STMN1 as a specific target of miR-101 and luciferase reporter assay was carried out to further confirm this discovery. …STMN1 expression was reduced by miR-101 mimic and increased by miR-101 inhibitor. We next found that STMN1 was elevated in PC and its expression was negatively correlated with miR-101 expression. Furthermore, STMN1 siRNA curbed cell proliferation and invasion, which was opposite to miR-101 inhibitor effect on PC progression and STMN1 siRNA attenuated miR-101 inhibitor effect on cell proliferation and invasion. In conclusion, miR-101 inhibited PC cell proliferation and invasion via regulating STMN1, which provided a potential therapeutic for PC patients. Show more

Keywords: MiR-101, pancreatic cancer, STMN1, proliferation, invasion

DOI: 10.3233/CBM-181675

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 301-309, 2018

Article Type: Other

DOI: 10.3233/CBM-179577

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 311-, 2018

Article Type: Other

DOI: 10.3233/CBM-179249

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 313-, 2018