Up-regulation of annexin A2 expression predicates advanced clinicopathological features and poor prognosis in hepatocellular carcinoma

Tumor Biology ◽  
2015 ◽  
Vol 36 (12) ◽  
pp. 9373-9383 ◽  
Author(s):  
Haijian Zhang ◽  
Min Yao ◽  
Wei Wu ◽  
Liwei Qiu ◽  
Wenli Sai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Annexin A2 ◽  
Clinicopathological Features

scholarly journals The Long Non-coding RNA LINC01133 Promotes Hepatocellular Carcinoma Progression by Sponging miR-199a-5p and Activating Annexin A2

2020 ◽  
Author(s):  
Dan Yin ◽  
Zhi-Qiang Hu ◽  
Chu-Bin Luo ◽  
Xiao-Yi Wang ◽  
Hao-Yang Xin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Western Blot ◽  
Copy Number ◽  
Poor Prognosis ◽  
Annexin A2 ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Qrt Pcr

Abstract Background: Long non-coding RNAs (lncRNAs) have been found to be functionally associated with cancer development and progression. Although copy number variations (CNVs) are common in hepatocellular carcinoma (HCC), little is known about how CNVs in lncRNAs affect HCC progression and recurrence.Methods: We analyzed the whole genome sequencing (WGS) data of matched cancerous and non-cancerous liver samples from 49 patients with HCC to identify lncRNAs with CNVs. The results were validated in another cohort of 238 paired HCC and non-tumor samples by TaqMan copy number assay. Kaplan-Meier analysis and the log-rank test were performed to determine the prognostic value of CNVs in lincRNAs. Loss- and gain-of-function studies were conducted to determine the biological functions of LINC01133 in vitro and in vivo. The competing endogenous RNAs (ceRNAs) mechanism was clarified by microRNA sequencing (miR-seq), quantitative real-time PCR (qRT-PCR), western blot, and dual-luciferase reporter analyses. The protein binding mechanism was confirmed by RNA pull-down, RNA immunoprecipitation (RIP), qRT-PCR, and western blot analyses.Results: Genomic copy number of LINC01133 was increased in HCC, which is positively related with the elevated expression of LINC01133. Increased copy number of LINC01133 predicted the poor prognosis in HCC patients. LINC01133 overexpression promoted proliferation, colony formation, migration, and invasion in vitro, and facilitated tumor growth and lung metastasis in vivo, whereas LINC01133 knockdown had the opposite effects. Mechanistically, LINC01133 acted as a sponge of miR-199a-5p, resulting in enhanced expression of SNAI1, which induced epithelial-mesenchymal transition (EMT) in HCC cells. In addition, LINC01133 interacted with Annexin A2 (ANXA2) to activate ANXA2/STAT3 signaling pathway.Conclusions: LINC01133 promotes HCC progression by sponging miR-199a-5p and interacting with ANXA2. LINC01133 CNV gain is predictive of poor prognosis in HCC patients undergoing curative resection.

scholarly journals Copper chaperone for superoxide dismutase expression is down-regulated and correlated with more malignant tumoral features and poor prognosis in human hepatocellular carcinoma

2020 ◽  
Author(s):  
Chun-yong Wen ◽  
Chang-liang Shan ◽  
Wen-jing Sun ◽  
Yuan Wan ◽  
Run Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Superoxide Dismutase ◽  
Expression Pattern ◽  
Poor Prognosis ◽  
Clinicopathological Features ◽  
Biological Behavior ◽  
Signal Pathways ◽  
Copper Chaperone ◽  
Lower Expression

Abstract Background: Up-regulated expression of copper chaperone for superoxide dismutase (CCS) is identified in a multitude of tumors and is closely related to more malignant tumoral biological behaviors. However, little is known about the role of CCS in hepatocellular carcinoma (HCC). This study aims to explore the expression pattern and the significance of CCS in human HCC.Methods Fresh samples of HCC with paired adjacent tissues, as well as the clinicopathological features and prognosis data were obtained from 32 patients who underwent hepatectomy from January 2018 to December 2018. The expression levels of CCS and a series of representative malignant biomarkers in HCC and adjacent tissues were investigated by western blotting and immunohistochemistry staining, respectively. The correlation between the expression status of CCS and the activities of selected malignant biomarkers and important drive genes of HCC oncogenesis, patient’s clinicopathological features and prognosis, were analyzed. Additional bioinformatics investigation of dataset retrieved from TCGA, the GEPIA, HPA, and Kaplan-Meier plotter (KM plotter) database were performed to further explore the role of CCS in human HCC and to validate the aforementioned findings. Results A unique express pattern was found that the majority of the HCC tumor (78.1%, 25/32) presented a lower expression of CCS as compared with that in adjacent tissues, whereas in the minority of the tumor (22.9%, 7/32) the expression of CCS was determined as higher. The distinctive CCS express status in HCC was further validated by the analysis of the data from TCGA and the GEPIA database. Furthermore, it was found that the expression level of CCS was significantly correlated with the those of the selected biomarkers including Ki67, vimentin, GPC3, and E-cadherin, which were also confirmed by the bioinformatic study. On the clinicopathological features, the expression of CCS was reversely correlated with ES grade and TNM stage to some extent, whereas there were no apparent correlations were proved with the remaining parameters included. Additional explorations revealed that there is a significant correlation between the CCS gene and a series of the driving/high-frequency mutation genes of various signal pathways in the development and progression of HCC. Despite statistic significant was not achieved, patients with higher CCS expression lever were prone to have a better prognosis. And a robust prognostic value of CCS was further proven in bioinformatic study. Conclusion HCC presented a unique lower expression pattern of CCS which reversely correlated with the more malignant tumoral features and poor prognosis as demonstrated by both experimental and bioinformatic studies. These findings improved our knowledge for understanding of the unique biological behavior of human HCC.

miR-224 is an early-stage biomarker of hepatocellular carcinoma with miR-224 and miR-125b as prognostic biomarkers

2020 ◽  
Vol 14 (15) ◽  
pp. 1485-1500
Author(s):  
Lichao Yang ◽  
Chunmeng Wei ◽  
Yasi Li ◽  
Xiao He ◽  
Min He
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Survival Analysis ◽  
Sensitivity And Specificity ◽  
Poor Prognosis ◽  
Early Stage ◽  
Meta Analysis ◽  
Benign Lesion ◽  
Diagnostic Efficiency ◽  
Low Expression

Aim: The aim was to systematically investigate the miRNA biomarkers for early diagnosis of hepatocellular carcinoma (HCC). Materials & methods: A systematic review and meta-analysis of miRNA expression in HCC were performed. Results: A total of 4903 cases from 30 original studies were comprehensively analyzed. The sensitivity and specificity of miR-224 in discriminating early-stage HCC patients from benign lesion patients were 0.868 and 0.792, which were superior to α-fetoprotein. Combined miR-224 with α-fetoprotein, the sensitivity and specificity were increased to 0.882 and 0.808. Prognostic survival analysis showed low expression of miR-125b and high expression of miR-224 were associated with poor prognosis. Conclusion: miR-224 had a prominent diagnostic efficiency in early-stage HCC, with miR-224 and miR-125b being valuable in the prognostic diagnosis.

Intra-platelet serotonin and YAP contributed to poor prognosis of hepatocellular carcinoma

Life Sciences ◽  
2021 ◽  
Vol 270 ◽  
pp. 119140
Author(s):  
Sushun Liu ◽  
Mimi Zhai ◽  
Wang Xiao ◽  
Qin Zhou ◽  
Dan Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Platelet Serotonin

scholarly journals Role of annexin A2 and osteopontin for early diagnosis of hepatocellular carcinoma in hepatitis C virus patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Abd El-Fattah F. Hanno ◽  
Fatma M. Abd El-Aziz ◽  
Akram A. Deghady ◽  
Ehab H. El-Kholy ◽  
Aborawy I. Aborawy
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Early Diagnosis ◽  
Positive Predictive Value ◽  
Negative Predictive Value ◽  
Chronic Hepatitis C ◽  
Predictive Value ◽  
Annexin A2 ◽  
Alpha Fetoprotein

Abstract Background Liver cancer is the fifth most common cancer and the second most frequent cause of cancer-related death globally. Early stages of hepatocellular carcinoma (0&A) can be treated with curative procedures. The aim of this work was to evaluate the role of annexin A2 and osteopontin for early diagnosis of hepatocellular carcinoma in hepatitis C virus patients. Methods The study was carried out on 80 patients classified into two groups. Group A had 40 chronic hepatitis C patients without hepatocellular carcinoma, while group B had 40 chronic hepatitis C patients with early hepatocellular carcinoma (stages; 0&A). All patients were subjected to thorough history taking, clinical examination, liver function tests, renal function tests, serum alpha-fetoprotein, serum osteopontin, and serum annexin A2. Results Serum alpha-fetoprotein was found to be statistically significantly higher in patients with the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for alpha-fetoprotein for detection of HCC was significant, its diagnostic performance was 0.818* (p < 0.001*), and the cutoff point for predicting the probability for HCC was 6.0 (ng/ml) with sensitivity of 77.50%, specificity of 82.50%, positive predictive value of 81.60%, negative predictive value of 78.6%, and accuracy of 80%. Serum osteopontin was found to be statistically significantly higher in patients from the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for osteopontin was significant, its diagnostic performance was 0.739* (p < 0.001*), the cutoff point was 13.2 (ng/ml) with sensitivity of 65.0%, specificity of 90.0%, positive predictive value of 86.70%, negative predictive value of 72.0%, and accuracy of 77.0%. Serum annexin A2 was found to be statistically significantly higher in patients from the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for annexin A2 was significant, its diagnostic performance was 0.927* (p < 0.001*), the cutoff point was 10.1(ng/ml) with sensitivity of 85.0%, specificity of 85.0%, positive predictive value of 85.0%, negative predictive value of 85.0%, and accuracy of 85.0%. Conclusions Osteopontin had better specificity but lower sensitivity than serum alpha-fetoprotein for early diagnosis of hepatocellular carcinoma. Annexin A2 had better diagnostic sensitivity and specificity than alpha-fetoprotein for early diagnosis of hepatocellular carcinoma.

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