scholarly journals Applying NGS Data to Find Evolutionary Network Biomarkers from the Early and Late Stages of Hepatocellular Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-27 ◽  
Author(s):  
Yung-Hao Wong ◽  
Chia-Chou Wu ◽  
Chih-Lung Lin ◽  
Ting-Shou Chen ◽  
Tzu-Hao Chang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systems Biology ◽  
Liver Cancer ◽  
Late Stage ◽  
Early Stage ◽  
Network Structures ◽  
Network Biomarkers ◽  
Two Stages ◽  
Ngs Data ◽  
Late Stages

Hepatocellular carcinoma (HCC) is a major liver tumor (~80%), besides hepatoblastomas, angiosarcomas, and cholangiocarcinomas. In this study, we used a systems biology approach to construct protein-protein interaction networks (PPINs) for early-stage and late-stage liver cancer. By comparing the networks of these two stages, we found that the two networks showed some common mechanisms and some significantly different mechanisms. To obtain differential network structures between cancer and noncancer PPINs, we constructed cancer PPIN and noncancer PPIN network structures for the two stages of liver cancer by systems biology method using NGS data from cancer cells and adjacent noncancer cells. Using carcinogenesis relevance values (CRVs), we identified 43 and 80 significant proteins and their PPINs (network markers) for early-stage and late-stage liver cancer. To investigate the evolution of network biomarkers in the carcinogenesis process, a primary pathway analysis showed that common pathways of the early and late stages were those related to ordinary cancer mechanisms. A pathway specific to the early stage was the mismatch repair pathway, while pathways specific to the late stage were the spliceosome pathway, lysine degradation pathway, and progesterone-mediated oocyte maturation pathway. This study provides a new direction for cancer-targeted therapies at different stages.

scholarly journals Evolution of Network Biomarkers from Early to Late Stage Bladder Cancer Samples

2014 ◽  
Vol 2014 ◽  
pp. 1-23 ◽  
Author(s):  
Yung-Hao Wong ◽  
Cheng-Wei Li ◽  
Bor-Sen Chen
Keyword(s):  
Bladder Cancer ◽  
Late Stage ◽  
Early Stage ◽  
Network Structures ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Network Biomarkers ◽  
Two Stages

We use a systems biology approach to construct protein-protein interaction networks (PPINs) for early and late stage bladder cancer. By comparing the networks of these two stages, we find that both networks showed very significantly different mechanisms. To obtain the differential network structures between cancer and noncancer PPINs, we constructed cancer PPIN and noncancer PPIN network structures for the two bladder cancer stages using microarray data from cancer cells and their adjacent noncancer cells, respectively. With their carcinogenesis relevance values (CRVs), we identified 152 and 50 significant proteins and their PPI networks (network markers) for early and late stage bladder cancer by statistical assessment. To investigate the evolution of network biomarkers in the carcinogenesis process, primary pathway analysis showed that the significant pathways of early stage bladder cancer are related to ordinary cancer mechanisms, while the ribosome pathway and spliceosome pathway are most important for late stage bladder cancer. Their only intersection is the ubiquitin mediated proteolysis pathway in the whole stage of bladder cancer. The evolution of network biomarkers from early to late stage can reveal the carcinogenesis of bladder cancer. The findings in this study are new clues specific to this study and give us a direction for targeted cancer therapy, and it should be validated in vivo or in vitro in the future.

scholarly journals The Emerging Factors and Treatment Options for NAFLD-Related Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3740
Author(s):  
Chunye Zhang ◽  
Ming Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Fatty Liver ◽  
Early Stage ◽  
Primary Liver Cancer ◽  
Treatment Options ◽  
Underlying Mechanism ◽  
Diagnostic Methods ◽  
T Cell Therapy ◽  
Nonalcoholic Fatty Liver

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, followed by cholangiocarcinoma (CCA). HCC is the third most common cause of cancer death worldwide, and its incidence is rising, associated with an increased prevalence of obesity and nonalcoholic fatty liver disease (NAFLD). However, current treatment options are limited. Genetic factors and epigenetic factors, influenced by age and environment, significantly impact the initiation and progression of NAFLD-related HCC. In addition, both transcriptional factors and post-transcriptional modification are critically important for the development of HCC in the fatty liver under inflammatory and fibrotic conditions. The early diagnosis of liver cancer predicts curative treatment and longer survival. However, clinical HCC cases are commonly found in a very late stage due to the asymptomatic nature of the early stage of NAFLD-related HCC. The development of diagnostic methods and novel biomarkers, as well as the combined evaluation algorithm and artificial intelligence, support the early and precise diagnosis of NAFLD-related HCC, and timely monitoring during its progression. Treatment options for HCC and NAFLD-related HCC include immunotherapy, CAR T cell therapy, peptide treatment, bariatric surgery, anti-fibrotic treatment, and so on. Overall, the incidence of NAFLD-related HCC is increasing, and a better understanding of the underlying mechanism implicated in the progression of NAFLD-related HCC is essential for improving treatment and prognosis.

scholarly journals CRYOSURGERY IN THE TREATMENT OF LIVER CANCER: A CASE REPORT

2019 ◽  
Vol 18 (4) ◽  
pp. 112-115
Author(s):  
N. V. Merzlikin ◽  
L. U. Petrov ◽  
V. F. Tskhai ◽  
E. A. Pshenichnikova ◽  
A. P. Sarueva
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Resection Margin ◽  
Imaging Techniques ◽  
Signs And Symptoms ◽  
Organ Damage ◽  
Right Hemihepatectomy ◽  
Patient Prognosis ◽  
Late Stages

Background. Hepatocellular carcinoma is the most common liver cancer and is a leading cause of cancerrelated death worldwide. Its aggressiveness and extensive dissemination lead to a poor patient prognosis. The 5-year survival rate does not exceed 15 %. Despite advances in imaging techniques, its curable rate remains low, because signs and symptoms of liver cancer do not usually appear until the late stages. There is no standard curative treatment for advanced liver cancer.Description. We present the case of a 56- year-old female patient with stage T3N0M0 hepatocellular carcinoma. The patient had a tumor of 20 cm in diameter and 2400 g in weight. The patient underwent right hemihepatectomy and cryodestruction of the liver stump along the resection margin. No evidence of tumor recurrence was found with a follow-up of 12 years.Conclusion. Cryodestruction of the liver stump along the resection margin increases the potential for a higher cure rate in patients with hepatocellular carcinoma, even in cases of extensive organ damage in the absence of metastasis and tumor ingrowth into surrounding organs. 

scholarly journals DNA Hypermethylation Modification Promotes the Development of Hepatocellular Carcinoma by Depressing the Tumor Suppressor Gene ZNF334

2021 ◽  
Author(s):  
Da-peng Sun ◽  
Xiao-jie Gan ◽  
Lei Liu ◽  
Yuan Yang ◽  
Dong-yang Ding ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Tumor Suppressor ◽  
Liver Cancer ◽  
Tumor Suppressor Gene ◽  
Clinical Evidence ◽  
Early Stage ◽  
Suppressor Gene ◽  
Dna Hypermethylation ◽  
Dysplastic Nodules

Abstract Background: DNA methylation plays a pivotal role in the development and progression of tumors, but studies focused on the dynamic changes of DNA methylation in the development of hepatocellular carcinoma (HCC) are rare. This manuscript is aimed to construct pre- and early DNA methylation maps of liver cancer of the same genetic background, as well as to reveal the mechanism of epigenetics regulating gene expression during the development of liver cancer, thus providing new targets and clinical evidence for early diagnosis and shedding lights on the precise treatment for liver cancer. Methods: The study includes 5 patients who were chronic hepatitis B virus infected, clinically diagnosed as primary liver cancer and pathologically diagnosed as early liver cancer with liver dysplastic nodules. Liver fibrosis tissues, dysplastic nodules and early HCC tissues from these patients have been used to measure DNA methylation. Results: We report significant differences in the DNA methylation spectrum of three types of tissues. In the early stage of HCC, DNA hypermethylation of tumor suppressor genes is predominant. Additionally, DNA hypermethylation in the early stage of HCC changes the binding of transcription factor P53 to the promoter of tumor suppressor gene ZNF334, and inhibits the expression of ZNF334 at the transcription level. Furthermore, through a series of in vivo and in vitro experiments, we have clarified the exacerbation effect of tumor suppressor gene ZNF334 deletion in the occurrence of HCC. Combined with clinical data, we found that the overall survival and disease-free survival of patients with high ZNF334 expression are longer than the lower one. Conclusions: We constructed a sequential map of DNA methylation modification during the occurrence of HCC, and clarified the biological function and regulatory mechanism of the tumor suppressor gene ZNF334, which is regulated by related DNA methylation sites, and also provide new targets and clinical evidence for the early diagnosis and precise treatment of liver cancer.

scholarly journals Validation of mRNAs in Early Diagnosis and Treatment of Hepatocellular Carcinoma

2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Iqra Khalid ◽  
Azra Quraishi ◽  
Freeha Fiaz
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Early Stage ◽  
Therapeutic Targets ◽  
Minimal Invasive ◽  
Detection Methods ◽  
Circulating Micrornas ◽  
Novel Biomarkers ◽  
Diseased State

Poor and late diagnosis of HCV is main the cause of liver cancer. MicroRNAs are non-coding molecules that are involved in regulation of a variety of functions happening in the cell, in healthy and diseased state. Dysregulation of microRNAs is observed in different diseases, especially in liver cancer like hepatocellular carcinoma. The available detection methods detect HCC at a late stage. There is a need to find novel biomarkers for diagnosis at an earlier stage to minimize chances of liver cancer. Circulating microRNAs are novel and minimal invasive markers for early detection of HCV based hepatocellular carcinoma. In this review, the current progress on the potential role of miRNA as biomarkers for detection of HCC and therapeutic targets are summarized. We concluded that the expression of microRNAis upregulated in the patients of hepatocellular carcinoma when compared with the healthy ones. In-depth studies of miRNA in patients of HCC as genetic biomarkers will improve the diagnosis. It will also improve the prognosis of early stage HCC patients. This will also help in identifying a suitable and effective therapeutic targets so as to reduce the chances of failure of chemotherapy.

scholarly journals Aspirin and 5-Aminoimidazole-4-carboxamide Riboside Attenuate Bovine Ephemeral Fever Virus Replication by Inhibiting BEFV-Induced Autophagy

2020 ◽  
Vol 11 ◽  
Author(s):  
Hsu-Hung Tseng ◽  
Wei-Ru Huang ◽  
Ching-Yuan Cheng ◽  
Hung-Chuan Chiu ◽  
Tsai-Ling Liao ◽  
...  
Keyword(s):  
Virus Replication ◽  
Late Stage ◽  
Early Stage ◽  
Bovine Ephemeral Fever Virus ◽  
Jnk Pathway ◽  
Bovine Ephemeral Fever ◽  
Attenuated Virus ◽  
Mtorc1 Pathway ◽  
Proteasome Pathway ◽  
Late Stages

Recent study in our laboratory has demonstrated that BEFV-induced autophagy via activation of the PI3K/Akt/NF-κB and Src/JNK pathways and suppression of the PI3K-AKt-mTORC1 pathway is beneficial for virus replication. In the current study, we found that both aspirin and 5-aminoimidazole-4-carboxamide-1-β-riboside (AICAR) siginificantly attenuated virus replication by inhibiting BEFV-induced autophagy via suppressing the BEFV-activated PI3K/Akt/NF-κB and Src/JNK pathways as well as inducing reversion of the BEFV-suppressed PI3K-Akt-mTORC1 pathway. AICAR reversed the BEFV-activated PI3K/Akt/NF-κB and Src/JNK pathways at the early to late stages of infection and induced reversion of the BEFV-suppressed PI3K-AKt-mTORC1 pathway at the late stage of infection. Our findings reveal that inhibition of BEFV-induced autophagy by AICAR is independent of AMPK. Furthermore, we found that AICAR transcriptionally downregulates the ATG related genes ULK1, Beclin 1, and LC3 and enhances Atg7 degradation by the proteasome pathway. Aspirin suppresses virus replication by inhibiting BEFV-induced autophagy. It directly suppressed the NF-κB pathway and reversed the BEFV-activated Src/JNK pathway at the early stage of infection and reversed the BEFV-suppressed PI3K/Akt/mTOR pathway at the late stage of infection. The current study provides mechanistic insights into the effects of aspirin and AICAR on BEFV replication through suppression of BEFV-induced autophagy.

scholarly journals Platelets’ RNA as biomarker trove for differentiation of early-stage hepatocellular carcinoma from underlying cirrhotic nodules

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256739
Author(s):  
Walifa Waqar ◽  
Sidra Asghar ◽  
Sobia Manzoor
Keyword(s):  
Hepatocellular Carcinoma ◽  
Late Stage ◽  
Liquid Biopsy ◽  
Early Stage ◽  
Quantitative Real Time Pcr ◽  
Roc Curve Analysis ◽  
Mrna Content ◽  
Early Hcc ◽  
Rising Incidence ◽  
Specific Mrna

Background & aims Among the multiplicity of factors involved in rising incidence of hepatocellular carcinoma (HCC)-the second deadliest cancer, late diagnosis of early-stage HCC nodules originating from late-stage cirrhotic nodules is the most crucial. In recent years, Tumor-educated platelets (TEPs) have emerged as a strong multimodal tool to be used in liquid-biopsy of cancers because of changes in their mRNA content. This study assessed the reliability of selected mRNA repertoire of platelets as biomarkers to differentiate early HCC from late-stage cirrhotic nodules. Methods Quantitative real time PCR (qRT-PCR) was used to evaluate expression levels of selected platelets-specific mRNA between HCC patients compared to cirrhosis patients. ROC curve analysis assessed the sensitivity and specificity of the biomarkers. Results RhoA, CTNNB1 and SPINK1 showed a significant 3.3-, 3.2- and 3.18-folds upregulation, respectively, in HCC patients compared to cirrhosis patients while IFITM3 and SERPIND1 presented a 2.24-fold change. Strikingly, CD41+ platelets also demonstrated a marked difference of expression in HCC and cirrhosis groups. Conclusions Our study reports liquid biopsy-based platelets mRNA signature for early diagnosis of HCC from underlying cirrhotic nodules. Moreover, differential expression of CD41+ platelets in two groups provides new insights into a probable link between CD41 expression on platelets with the progression of cirrhosis to HCC.

Physical Health in Early and Late Stages of Bipolar Disorder

2017 ◽  
Vol 41 (S1) ◽  
pp. s113-s113
Author(s):  
M.P. García-Portilla ◽  
L. de la Fuente-Tomás ◽  
L. García-Álvarez ◽  
P. Sierra ◽  
B. Arranz ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Physical Health ◽  
Late Stage ◽  
Early Stage ◽  
Biological Information ◽  
Abdominal Circumference ◽  
Multisystem Disorder ◽  
Cross Sectional ◽  
Somatic Comorbidities ◽  
Late Stages

IntroductionBipolar disorder (BD) is related to high prevalence of somatic comorbidities, health care costs, and premature mortality [1]. Some evidence supports the view of BD as chronic, progressive and multisystem disorder in which not only mental system, but also somatic systems are involved [2].AimTo investigate differences in physical health in patients with bipolar disorder at different stages (early vs. late) of the disease.MethodsCross-sectional, naturalistic, multicenter study. Sample: 110 outpatients with BD [68 early stage (diagnosed at least 5 years earlier) and 42 late stage (at least 20 years earlier)]. Assessment: demographic and clinical variables; psychopathology: HDRS, YMRS and CGI; biological information: anthropometric, vital signs and lab results.ResultsEarly stage group: mean age 40.1 (11.9), 66.2% females and CGI = 3.6 (1.4). Late stage group: mean age 55.8 (8.2), 69.0% females and CGI = 4.0 (1.4). Patients in early stage have significantly higher levels of glucose (t = −4.007, P < 0.001), urea (t = −2.724, P = 0.008), creatinine (F = 0.560, P = 0.022), triglycerides (t = −3.501, P = 0.001), Fe (t = 2.871, P = 0.005) and insulin (t = −3.223, P = 0.002). Moreover, they have higher Body Max Index (BMI) (t = −3.728, P < 0.000), abdominal circumference (t = −4.040, P < 0.000) and greater number of somatic comorbidities (t = −2.101, P = 0.041).Conclusions– patients with bipolar disorders in late stages have worse physical health than those in early stage.– these results could be an indication that bipolar disorder might better viewed as a multisystem disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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