First evaluation of Neighbor of Punc E11 (NOPE) as a novel marker in human hepatocellular carcinoma

2020 ◽  
pp. 1-9
Author(s):  
Susanne Zweerink ◽  
Senait Mesghenna ◽  
Vera Mueck ◽  
Sigrid Schulte ◽  
Fabian Kuetting ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
Cancer Death ◽  
Adult Liver ◽  
Epithelial Tumor ◽  
Common Cause ◽  
Qrt Pcr ◽  
Potential Biomarker

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide and the search for clinically useful biomarkers is ongoing. Neighbor of Punc E11 (NOPE) is an established biomarker of murine HCC that remains undetectable in normal liver and at preneoplastic stages. OBJECTIVE: The aim of our study was to evaluate the presence of NOPE in human HCC. METHODS: Histologically confirmed HCC and corresponding non-tumor liver samples from 20 patients were analyzed for expression of NOPE using qRT-PCR and mRNA-in-situ technology in a conserved tissue context. RESULTS: In our cohort, 30% of HCC samples were expressing NOPE which proved particularly useful in non-cirrhotic HCC samples with up to 155-fold higher expression than in adult liver. Using mRNA-in-situ technology, NOPE was clearly identified within epithelial tumor cells of NOPE positive human HCCs. In our analyzed cohort, the combination of AFP with NOPE did not reach more than 40% sensitivity while GPC-3 and NOPE were complementary to each other reaching a combined sensitivity of 85.7%. CONCLUSIONS: This is the first characterization of NOPE as a potential biomarker for human HCC. Our results underline the value of NOPE as a complementing biomarker for human HCC.

scholarly journals Circular RNA Hsa_Circ_0091579 Serves as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

2018 ◽  
Vol 51 (1) ◽  
pp. 290-300 ◽  
Author(s):  
Chenxing Zhang ◽  
Chenyue Zhang ◽  
Jiamao Lin ◽  
Haiyong Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Tumors ◽  
Expression Profiles ◽  
Critical Role ◽  
Roc Curves ◽  
Altered Expression ◽  
Qrt Pcr ◽  
Specificity And Sensitivity ◽  
Tumor Tissues ◽  
Potential Biomarker

Background/Aims: An increasing number of studies have suggested that circular RNAs (circRNAs) have vital roles in carcinogenesis and tumor progression. However, the function of circRNAs in hepatocellular carcinoma (HCC) remains poorly characterized. Methods: We investigated the levels of circRNAs in patients with HCC to identify potential diagnostic biomarkers. We examined circRNA expression profiles in liver tumors and paired non-cancerous liver tissues from three HCC patients with cancer thrombus using a circRNA microarray. Bioinformatics analysis was performed to find circRNAs with significantly altered expression levels between tumors and their paired non-tumor tissues. We confirmed our initial findings by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curves were also applied to identify a candidate circRNA with the optimal specificity and sensitivity. Finally, X-tile software was adopted to calculate the most efficient cut-off value for hsa_circ_0091579 expression. Results: Microarray analysis identified 20 unique circRNAs that were differentially expressed between tumor and non-tumor tissues (P < 0.05). The expression of these 20 circRNAs was verified by qRT-PCR. The expression of hsa_circ_16245-1 and hsa_circ_0091579 mRNA was consistent with their levels as tested by the microarray. The ROC curves showed that both hsa_circ_16245-1 and hsa_circ_0091579 had favorable specificity and sensitivity. We further confirmed that hsa_circ_0091579 was significantly upregulated in HCC and its high expression was intimately associated with a worse overall survival in patients with HCC. Conclusion: Hsa_circ_0091579 may play a critical role in HCC progression and serve as a potential biomarker for the prognosis of patients with HCC.

scholarly journals Characterization of the Merkel Cell Carcinoma miRNome

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Matthew S. Ning ◽  
Annette S. Kim ◽  
Nripesh Prasad ◽  
Shawn E. Levy ◽  
Huiqiu Zhang ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Normal Skin ◽  
Merkel Cell ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Skin Cancers ◽  
Next Generation Sequencing Ngs

MicroRNAs have been implicated in various skin cancers, including melanoma, squamous cell carcinoma, and basal cell carcinoma; however, the expression of microRNAs and their role in Merkel cell carcinoma (MCC) have yet to be explored in depth. To identify microRNAs specific to MCC (MCC-miRs), next-generation sequencing (NGS) of small RNA libraries was performed on different tissue samples including MCCs, other cutaneous tumors, and normal skin. Comparison of the profiles identified several microRNAs upregulated and downregulated in MCC. For validation, their expression was measured via qRT-PCR in a larger group of MCC and in a comparison group of non-MCC cutaneous tumors and normal skin. Eight microRNAs were upregulated in MCC: miR-502-3p, miR-9, miR-7, miR-340, miR-182, miR-190b, miR-873, and miR-183. Three microRNAs were downregulated: miR-3170, miR-125b, and miR-374c. Many of these MCC-miRs, the miR-183/182/96a cistron in particular, have connections to tumorigenic pathways implicated in MCC pathogenesis.In situhybridization confirmed that the highly expressed MCC-miR, miR-182, is localized within tumor cells. Furthermore, NGS and qRT-PCR reveal that several of these MCC-miRs are highly expressed in the patient-derived MCC cell line, MS-1. These data indicate that we have identified a set of MCC-miRs with important implications for MCC research.

Advances in delivery vectors for gene therapy in liver cancer

2020 ◽  
Vol 11 (1) ◽  
pp. 833-850 ◽  
Author(s):  
Katherine E Redd Bowman ◽  
Phong Lu ◽  
Erica R Vander Mause ◽  
Carol S Lim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Therapy ◽  
Viral Vectors ◽  
Gene Editing ◽  
Cancer Death ◽  
Common Cause ◽  
The Third ◽  
Gene Delivery Vectors ◽  
Efficient Delivery ◽  
Therapy Delivery

Hepatocellular carcinoma (HCC) is the third most common cause of cancer death globally, mainly due to lack of effective treatments – a problem that gene therapy is poised to solve. Successful gene therapy requires safe and efficient delivery vectors, and recent advances in both viral and nonviral vectors have made an important impact on HCC gene therapy delivery. This review explores how adenoviral, retroviral and adeno-associated viral vectors have been modified to increase safety and delivery capacity, highlighting studies and clinical trials using these vectors for HCC gene therapy. Nanoparticles, liposomes, exosomes and virosomes are also featured in their roles as HCC gene delivery vectors. Finally, new discoveries in gene editing technology and their impacts on HCC gene therapy are discussed.

scholarly journals RNA-Seq profiling revealed PBMC RNA as potential biomarker for hepatocellular carcinoma

2020 ◽  
Author(s):  
Zhiyi Han ◽  
Wenxing Feng ◽  
Rui Hu ◽  
Qinyu Ge ◽  
Wenfeng Ma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Rna Seq ◽  
Sequencing Data ◽  
Peripheral Blood Mononuclear ◽  
Qrt Pcr ◽  
Potential Biomarker ◽  
Incidence And Mortality ◽  
Differential Expressed Gene

Abstract Background Hepatocellular carcinoma is one of the most common malignancies with extremely high incidence and mortality rates. Although there have been many studies focus on biomarkers study, few have been reported on PBMC RNA profiles of hepatocellular carcinoma. Methods In this study, we attempted to profile the expression of Peripheral Blood Mononuclear Cells (PBMCs) RNA by using RNA-seq technology and compared the transcriptome between hepatocellular carcinoma patients and the healthy controls. 17 patients and 17 healthy controls involved in this study, PBMCs RNA were sequenced. The sequencing data were analyzed with bioinformatics tools and qRT-PCR was used for selected differential expressed gene validation. Results It is showed that 1578 dysregulated genes found including 1334 upregulated genes and 244 downregulated genes. GO enrichment and KEGG analysis denoted most of the differential expressed genes (DEGs) involved in immune response are closely related to hepatocellular carcinoma. Expression of the 6 selected genes (DEGs, SELENBP1, SLC4A1, SLC26A8, HSPA8P4, CALM1, and RPL7p24) were confirmed by qRT-PCR, and higher sensitivity and specificity obtained by ROC analysis of the 6 genes. CALM1 was found gradually decreasing along with the tumor enlarged. Conclusions It is suggested potential biomarker for diagnosis, classification and therapeutic target of hepatocellular carcinomas. This study provided new visions into development of liver cancer and potential efficient clinical diagnosis in the future.

Elasticity Characterization of Liver Cancers Using Shear Wave Ultrasound Elastography: Comparison Between Hepatocellular Carcinoma and Liver Metastasis

2017 ◽  
Vol 33 (6) ◽  
pp. 481-488 ◽  
Author(s):  
Kah Lai Choong ◽  
Yin How Wong ◽  
Chai Hong Yeong ◽  
Gnana Kumar Gnanasuntharam ◽  
Khean Lee Goh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Metastasis ◽  
Shear Wave ◽  
Liver Tissue ◽  
Normal Liver ◽  
Ultrasound Elastography ◽  
Normal Liver Tissue ◽  
Tissue Elasticity ◽  
Liver Cancers

Purpose: This was a feasibility study of shear wave ultrasound elastography for characterization of liver tumors and to compare the tissue elasticity values of hepatocellular carcinoma (HCC), liver metastases, and normal liver tissues. Methods: Forty-one patients and 30 healthy volunteers were recruited and categorized into HCC, liver metastasis, and control groups based on their computed tomography and sonographic examinations. Elasticity values of different groups were compared statistically. Results: Mean (standard deviation) elasticity values for HCC, liver metastasis, and normal liver tissue were 51.45 (14.96), 49.89 (13.82), and 6.63 (1.65) kilopascal, respectively. Statistically significant differences were found between the elasticity values of HCC and liver metastasis with normal liver tissue. Based on the receiver operating characteristics analysis, 18.25 kilopascal may differentiate the malignant focal liver lesions from the normal liver tissue with both sensitivity and specificity of 100%. Conclusion: Shear wave ultrasound elastography may be able to differentiate HCC and liver metastasis from normal liver tissue based on the tissue elasticity values.

scholarly journals Abdominal Ultrasound and Treatment of Hepatocellular Carcinoma

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1268
Author(s):  
Kazushi Numata
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Abdominal Ultrasound ◽  
Cancer Death ◽  
Common Cause ◽  
Cancer Statistics ◽  
The Third ◽  
Common Cancer

Liver cancer is the sixth most common cancer and the third most common cause of cancer death, based on Global Cancer Statistics 2020 [...]

scholarly journals Serum Exosomal MicroRNA, miR-10b-5p, as a Potential Diagnostic Biomarker for Early-Stage Hepatocellular Carcinoma

2020 ◽  
Vol 9 (1) ◽  
pp. 281 ◽  
Author(s):  
Hyo Cho ◽  
Jung Eun ◽  
Geum Baek ◽  
Chul Seo ◽  
Hye Ahn ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Validation Cohort ◽  
Early Stage ◽  
Area Under The Curve ◽  
Disease Free Survival ◽  
Pcr Analysis ◽  
Serum Samples ◽  
Qrt Pcr ◽  
Normal Hepatocyte ◽  
Potential Biomarker

Exosomal microRNAs (exo-miRs) have been promising cancer biomarkers. MiRs in hepatocellular carcinoma (HCC) cell-derived exosomes (HEX) were analyzed to identify reliable serum biomarkers for HCC. To detect overexpressed miRs in HEX, extracted exosomal small RNAs from human HCC cell lines and normal hepatocytes were sequenced and analyzed. Clinical significance of the overexpressed miRs in HEX was evaluated using quantitative real-time PCR (qRT-PCR) on serum samples of a validation cohort consisting of 28 healthy individuals, 60 with chronic liver disease, and 90 with HCC. We found 49 significantly overexpressed miRs in HEX compared to a normal hepatocyte. Among them, miR-10b-5p, miR-18a-5p, miR-215-5p, and miR-940 were overexpressed in HCC tissues and also associated with prognosis of HCC in the analysis of a public omics database. qRT-PCR analysis of the four serum exo-miRs in the validation cohort revealed serum exo-miR-10b-5p as a promising biomarker for early-stage HCC with 0.934 area under the curve (AUC) (sensitivity, 90.7%; specificity, 75.0%; cutoff value, 1.8-fold). Overexpression of serum exo-miR-215-5p was found to be significantly associated with poor disease-free survival in patients with HCC. Serum exo-miR-10b-5p is a potential biomarker for early-stage HCC, while serum exo-miR-215-5p can be used as prognostic biomarker for HCC.

scholarly journals RNA-Seq Profiling Revealed PBMC RNA as Potential Biomarker for Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Zhiyi Han ◽  
Wenxing Feng ◽  
Rui Hu ◽  
Qinyu Ge ◽  
Wenfeng Ma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mononuclear Cells ◽  
Malignant Tumors ◽  
High Morbidity ◽  
Healthy Controls ◽  
Rna Seq ◽  
Sequencing Data ◽  
Qrt Pcr ◽  
Potential Biomarker ◽  
Response Expression

Abstract Background: Hepatocellular carcinoma with extremely high morbidity and mortality is one of the most common malignant tumors. Although many existing studies focus on the study of its biomarkers, little information has been released on the PBMC RNA profile of hepatocellular carcinoma. Methods: We tried to make a profile throughout this analysis with the expression of Peripheral Blood Mononuclear Cells (PBMCs) RNA by using RNA-seq technology and compared the transcriptome between hepatocellular carcinoma patients and the healthy controls. 17 patients and 17 healthy controls involved in this study, PBMCs RNA were sequenced. The sequencing data were analyzed with bioinformatics tools and qRT-PCR was used for selected differential expressed gene validation. Results: It is showed that 1578 dysregulated genes found including 1334 upregulated genes and 244 downregulated genes. GO enrichment and KEGG studies showed that hepatocellular carcinoma is a closely linked source of the most differentially expressed genes (DEGs), implicated in the immune response. Expression of the 6 selected genes (SELENBP1, SLC4A1, SLC26A8, HSPA8P4, CALM1, and RPL7p24) were confirmed by qRT-PCR, and higher sensitivity and specificity obtained by ROC analysis of the 6 genes. CALM1 was found gradually decreasing along with the tumor enlarged. Conclusions: It is suggested potential biomarker for diagnosis of hepatocellular carcinomas. This study provided new perspectives for liver cancer development and possible future successful clinical diagnosis.

scholarly journals Identification of CDC25C as a Potential Biomarker in Hepatocellular Carcinoma Using Bioinformatics Analysis

2020 ◽  
Vol 19 ◽  
pp. 153303382096747
Author(s):  
Ruifeng Xun ◽  
Hougen Lu ◽  
Xianwang Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bioinformatics Analysis ◽  
Disease Free Survival ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Normal Liver ◽  
High Rate ◽  
Specific Gene ◽  
Ppi Networks ◽  
Potential Biomarker

Hepatocellular carcinoma (HCC) is the most aggressive type of gastrointestinal tumor, with a high rate of mortality. However, identifying biomarkers for the treatment of HCC remains to be developed. We aimed to determine whether cell division cycle 25C (CDC25C) could be used as a novel diagnostic and therapeutic biomarker in HCC. Expression of CDC25C in HCC was analyzed by using GEPIA (Gene Expression Profiling Interactive Analysis) and UALCAN databases. GEPIA and CBioPortal databases were applied to analyze patients’survival and CDC25C mutations, respectively. PPI (Protein-Protein Interaction) network was further built by STRING (Search Tool for the Retrieval of Interacting Genes) and Metascape Web portals. To the best of our knowledge, the novel observations identified in the present study reveal that the expression of CDC25C in HCC was significantly enhanced when compare to that in normal liver tissues (P < 0.001). A higher CDC25C expression resulted in a remarkably shorter disease free survival as well as overall survival. Moreover, the expression of CDC25C in HCC was related to HCC patients’grade and race, but not gender. The expression levels of CDC25C elevated gradually from stage 1 to 3 but decreased in stage 4. The specific gene mutations V41A, L87 H, N222 K and X309-splice of CDC25C occurred in HCC samples and these unique mutations were not detected in any other tumor tissues. Finally, PPI networks and GO enrichment analysis suggested that CDC25C might be associated with cell cycle and p53 signaling pathway. Taken together, bioinformatics analysis revealed that CDC25C might be a potential diagnostic predictor for HCC.

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