scholarly journals OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin Signaling

2021 ◽  
Vol 11 ◽  
Author(s):  
Shize Ma ◽  
Lei Duan ◽  
Huateng Dong ◽  
Xiaodong Ma ◽  
Xinyu Guo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Overall Survival ◽  
Survival Analysis ◽  
Poor Prognosis ◽  
Glioma Cells ◽  
Underlying Mechanism ◽  
Molecular Function ◽  
Potential Therapeutic Target ◽  
Kaplan Meier ◽  
Dependent Cell

Glioma is a highly heterogeneous and lethal tumor with an extremely poor prognosis. Through analysis of TCGA data, we identified that OLFML2A is a key promotor of gliomagenesis. However, the molecular function of OLFML2A and its underlying mechanism of action in glioma remain unclear. In this study, we found that OLFML2A expression was significantly upregulated in glioma specimens and positively correlated with pathological grades in glioma patients. Moreover, Kaplan–Meier survival analysis of TCGA data revealed that glioma patients with higher OLFML2A expression had shorter overall survival. Importantly, OLFML2A knockdown in glioma cells inhibited cell proliferation and promoted apoptosis. Mechanistically, OLFML2A downregulation inhibits Wnt/β-catenin signaling by upregulating amyloid precursor protein (APP) expression and reducing stabilized β-catenin levels, leading to the repression of MYC, CD44, and CSKN2A2 expression. Furthermore, OLFML2A downregulation suppressed the growth of transplanted glioma subcutaneously and intracranially by inhibiting Wnt/β-catenin pathway-dependent cell proliferation. By uncovering the oncogenic effects in human and rodent gliomas, our data support OLFML2A as a potential therapeutic target for glioma.

scholarly journals OLFML2A Downregulation Inhibits Glioma Proliferation through Suppression of Wnt/β-catenin Signaling

2020 ◽  
Author(s):  
Shize Ma ◽  
Lei Duan ◽  
Huateng Dong ◽  
Xiaodong Ma ◽  
Xinyu Guo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Underlying Mechanism ◽  
Kaplan Meier ◽  
Proliferation And Apoptosis ◽  
Spectral Computed Tomography ◽  
Dependent Cell ◽  
Apoptosis Gene ◽  
Tomography Scan ◽  
Worse Prognosis

Abstract Background: Glioma is a highly heterogeneous and lethal tumor with extremely poor prognosis. Through analysis of TCGA data, we found that OLFML2A was significantly upregulated in glioma tissues and positively correlated with glioma grade and worse prognosis. However, the molecular function of OLFML2A and its underlying mechanism in glioma remain unclear.Methods: The expression of OLFML2A in glioma was determined by immunohistochemistry (IHC). Celigo assay, MTT assay and flow cytometry were utilized to evaluate the effects of OLFML2A on glioma proliferation and apoptosis. Gene chip microarray analysis and ingenuity pathway analysis were used to investigate the potential regulatory mechanisms of OLFML2A, which were further assessed by q-PCR, western blotting and IHC. An animal transplanting glioma model and spectral computed tomography scan were used to verify OLFML2A expression in vivo.Results: In this study, we found that the expression of OLFML2A was significantly upregulated in glioma specimens and positively correlated with pathological grades in glioma patients. Moreover, Kaplan-Meier survival analysis of TCGA data revealed that glioma patients with higher expression of OLFML2A had shorter overall survival. Importantly, when we knocked down the expression of OLFML2A in glioma cells, cell proliferation was inhibited, and apoptosis was promoted. Mechanistically, downregulation of OLFML2A inhibited Wnt/β-catenin signaling by directly reducing the level of stabilized β-catenin and upregulating the expression of amyloid precursor protein (APP) to indirectly suppress β-catenin, leading to repression of MYC, CD44 and CSKN2A2 expression. Furthermore, we found that OLFML2A downregulation clearly suppressed the growth of subcutaneous glioma and intracranial transplantation of glioma by inhibiting Wnt/β-catenin pathway-dependent cell proliferation.Conclusion: Our data indicate the oncogenic effect of OLFML2A in glioma through regulation of Wnt/β-catenin signaling, which may provide a novel therapeutic target for glioma.

scholarly journals OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin Signaling

2020 ◽  
Author(s):  
Shize Ma ◽  
Lei Duan ◽  
Huateng Dong ◽  
Xiaodong Ma ◽  
Xinyu Guo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Underlying Mechanism ◽  
Kaplan Meier ◽  
Proliferation And Apoptosis ◽  
Spectral Computed Tomography ◽  
Dependent Cell ◽  
Apoptosis Gene ◽  
Tomography Scan ◽  
Worse Prognosis

Abstract Background: Glioma is a highly heterogeneous and lethal tumor with extremely poor prognosis. Through analysis of TCGA data, we found that OLFML2A was significantly upregulated in glioma tissues and positively correlated with glioma grade and worse prognosis. However, the molecular function of OLFML2A and its underlying mechanism in glioma remain unclear.Methods: The expression of OLFML2A in glioma was determined by immunohistochemistry (IHC). Celigo assay, MTT assay and flow cytometry were utilized to evaluate the effects of OLFML2A on glioma proliferation and apoptosis. Gene chip microarray analysis and ingenuity pathway analysis were used to investigate the potential regulatory mechanisms of OLFML2A, which were further assessed by q-PCR, western blotting and IHC. An animal transplanting glioma model and spectral computed tomography scan were used to verify OLFML2A expression in vivo.Results: In this study, we found that the expression of OLFML2A was significantly upregulated in glioma specimens and positively correlated with pathological grades in glioma patients. Moreover, Kaplan-Meier survival analysis of TCGA data revealed that glioma patients with higher expression of OLFML2A had shorter overall survival. Importantly, when we knocked down the expression of OLFML2A in glioma cells, cell proliferation was inhibited, and apoptosis was promoted. Mechanistically, downregulation of OLFML2A inhibited Wnt/β-catenin signaling by directly reducing the level of stabilized β-catenin and upregulating the expression of amyloid precursor protein (APP) to indirectly suppress β-catenin, leading to repression of MYC, CD44 and CSKN2A2 expression. Furthermore, we found that OLFML2A downregulation clearly suppressed the growth of subcutaneous glioma and intracranial transplantation of glioma by inhibiting Wnt/β-catenin pathway-dependent cell proliferation.Conclusion: Our data indicate the oncogenic effect of OLFML2A in glioma through regulation of Wnt/β-catenin signaling, which may provide a novel therapeutic target for glioma.

scholarly journals Eight-Gene Metabolic Signature Related with Tumor-Associated Macrophages Predicting Overall Survival for Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Junyu Huo ◽  
Yunjin Zang ◽  
Hongjing Dong ◽  
Xiaoqiang Liu ◽  
Fu He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Survival Analysis ◽  
Risk Score ◽  
Risk Group ◽  
Cancer Genome ◽  
Metabolic Reprogramming ◽  
Tumor Associated Macrophages ◽  
Kaplan Meier ◽  
The Relationship

Abstract Background: In recent years, the relationship between tumor associated macrophages (TAMs) and solid tumors has become a research hotspot. The study aims at exploring the close relationship of TAMs with metabolic reprogramming genes in hepatocellular carcinoma(HCC), in order to provide a new way of treatment for HCC.Materials and methods: The study selected 343 HCC patients with complete survival information(survival time >= 1month) in the Cancer Genome Atlas (TCGA) as the study objects. Kaplan-Meier survival analysis assisted in figuring out the relationship between macrophage infiltration level and overall survival (OS), and Pearson correlation test to identify metabolic reprogramming genes(MRGs) related to tumor macrophage abundance. Lasso regression algorithm were conducted on prognosis related MRGs screened by Univariate Cox regression analysis and Kaplan-Meier survival analysis to construct the riskscore, another independent cohort (including 228 HCC patients) from the International Cancer Genome Consortium (ICGC) were used for external validation regarding the prognostic signature.Results: A risk score composed of 8 metabolic genes can accurately predict the OS of training cohort(TCGA) and testing cohort(ICGC). It is important that the risk score could widely used for people with different clinical characteristics, and is an independent predictor independent of other clinical factors affecting prognosis. As expected, high-risk group exhibited an obviously higher macrophage abundance relative to low-risk group, and the risk score presented a positive relation to the expression level of three commonly used immune checkpoints(PD1,PDL1,CTLA4).Conclusion: Our study constructed and validated a novel eight‑gene signature for predicting HCC patients’ OS, which possibly contributed to making clinical treatment decisions.

scholarly journals Co-Expression of Coxsackievirus/Adenovirus Receptors and Desmoglein 2 in Lung Adenocarcinoma: A Comprehensive Analysis of Bioinformatics and Tissue Microarrays

2020 ◽  
Vol 9 (11) ◽  
pp. 3693
Author(s):  
Ching-Fu Weng ◽  
Chi-Jung Huang ◽  
Mei-Hsuan Wu ◽  
Henry Hsin-Chung Lee ◽  
Thai-Yen Ling
Keyword(s):  
Overall Survival ◽  
Survival Analysis ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
The Cancer Genome Atlas ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Kaplan Meier

Introduction: Coxsackievirus/adenovirus receptors (CARs) and desmoglein-2 (DSG2) are similar molecules to adenovirus-based vectors in the cell membrane. They have been found to be associated with lung epithelial cell tumorigenesis and can be useful markers in predicting survival outcome in lung adenocarcinoma (LUAD). Methods: A gene ontology enrichment analysis disclosed that DSG2 was highly correlated with CAR. Survival analysis was then performed on 262 samples from the Cancer Genome Atlas, forming “Stage 1A” or “Stage 1B”. We therefore analyzed a tissue microarray (TMA) comprised of 108 lung samples and an immunohistochemical assay. Computer counting software was used to calculate the H-score of the immune intensity. Cox regression and Kaplan–Meier analyses were used to determine the prognostic value. Results: CAR and DSG2 genes are highly co-expressed in early stage LUAD and associated with significantly poorer survival (p = 0.0046). TMA also showed that CAR/DSG2 expressions were altered in lung cancer tissue. CAR in the TMA was correlated with proliferation, apoptosis, and epithelial–mesenchymal transition (EMT), while DSG2 was associated with proliferation only. The Kaplan–Meier survival analysis revealed that CAR, DSG2, or a co-expression of CAR/DSG2 was associated with poorer overall survival. Conclusions: The co-expression of CAR/DSG2 predicted a worse overall survival in LUAD. CAR combined with DSG2 expression can predict prognosis.

scholarly journals FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Weixing Dai ◽  
Xianke Meng ◽  
Shaobo Mo ◽  
Wenqiang Xiang ◽  
Ye Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Poor Prognosis ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Underlying Mechanism ◽  
Low Expression

Abstract Background Low expression of FOXE1, a member of Forkhead box (FOX) transcription factor family that plays vital roles in cancers, contributes to poor prognosis of colorectal cancer (CRC) patients. However, the underlying mechanism remains unclear. Materials and methods The effects of FOXE1 on the growth of colon cancer cells and the expression of glycolytic enzymes were investigated in vitro and in vivo. Molecular biological experiments were used to reveal the underlying mechanisms of altered aerobic glycolysis. CRC tissue specimens were used to determine the clinical association of ectopic metabolism caused by dysregulated FOXE1. Results FOXE1 is highly expressed in normal colon tissues compared with cancer tissues and low expression of FOXE1 is significantly associated with poor prognosis of CRC patients. Silencing FOXE1 in CRC cell lines dramatically enhanced cell proliferation and colony formation and promoted glucose consumption and lactate production, while enforced expression of FOXE1 manifested the opposite effects. Mechanistically, FOXE1 bound directly to the promoter region of HK2 and negatively regulated its transcription. Furthermore, the expression of FOXE1 in CRC tissues was negatively correlated with that of HK2. Conclusion FOXE1 functions as a critical tumor suppressor in regulating tumor growth and glycolysis via suppressing HK2 in CRC.

Combined Measurement of Plasma Cell Proliferation and Apoptosis in Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4884-4884
Author(s):  
Jiri Minarik ◽  
Vlastimil Scudla ◽  
Marta Ordeltova ◽  
Tomas Pika ◽  
Jaroslav Bacovsky ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Cell Proliferation ◽  
Overall Survival ◽  
Plasma Cell ◽  
Poor Prognosis ◽  
Apoptotic Index ◽  
Number Of Patients ◽  
Proliferation And Apoptosis ◽  
Extreme Groups

Abstract Abstract 4884 Background Plasma cell proliferation and apoptosis represent key factors in multiple myeloma (MM) expansion and tumor survival. Both the proliferative and the apoptotic index have been shown to be strong and independent prognosticators in MM. Moreover, they do not correlate with most standard prognostic factors, representing thus different inherent features of the myeloma clone. The aim of the study was to assess the combined measurement of proliferation and apoptosis, giving the best predictive value for long and short MM survivals. Methods We assessed a cohort of 181 patients with newly diagnosed multiple myeloma, treated using conventional chemotherapy (regimens MP, VBMCP, VAD, CyVAD). In all the patients we measured proliferative and apoptotic index at the time of diagnosis, before the start of treatment. The proliferative activity of myeloma plasmocytes in bone marrow aspirate was measured by flow- cytometry using propidium-iodide index (PC-PI), representing the percentage of plasma cells in S-phase of the cell cycle; apoptosis was assessed using flow cytometry using an annexin-V (PC-AI) index. Subsequent statistical analysis of the the Kaplan-Meier curves of overall survival was evaluated using the MATLAB routine. We assessed different PC-PI and PC-AI tresholds with the best separation of groups with good and poor prognosis, using the log rank procedure. Additional measures of performance were obtained looking at the success with which two groups selected using the PC-AI and PC-PI thresholds reflected short term and long term survivors. Results The median follow-up of the group was 25 months (range 1 – 117 months). At the time of analysis, 137 patients had died (76%). Plasma cell proliferative index varied in the range 1.2 – 4.2, with median 2.5; apoptotic index was in the range 1.4 – 24.5 with median 4.3. Patients were divided into 4 groups based on PC-PI and PC-AI thresholds and then keeping only those two groups that demonstrated the worst and best overall survival based on the survival analysis of PC-PI and PC-AI individually. The best discriminating values for patients with poor prognosis (n=20) were PC-PI > 3.0% and PC-AI < 4.75%, and for patients with good prognosis (n = 71) PC-PI ' 3.0% and PC-AI ≥ 4.75%, with median overall survival 8 months versus 40 months respectively, p = 0.0002. The precision of the correct prediction of individual patient prognosis based on this grouping was in the patients with short survival 0.70 and in long survivors 0.58. Due to an imbalanced number of patients especially with high proliferation we were unable to create a single significant combined index across the entire patient group. Moreover, the patients outside the defined ranges substantially influenced the sensitivity and especially the specificity of the test, suggesting that defining of the extreme groups using PC-PI and PC-AI creates a better prognosticator than the assessment of the whole cohort based on a single combined index. Conclusion Plasma cell proliferation and apoptosis reflect different processes of MM kinetics with the growth characteristics on one hand, and survival on the other. Their assessment as single factors provides valuable information about the biology of the clone and contributes to the estimation of overall survival. Their combined measurement, however, significantly separates two extreme groups of patients with different prognosis and may thus become a valuable auxiliary parameter in MM patients stratification. Disclosures No relevant conflicts of interest to declare.

Incidence and characterization of venous thromboembolic events (VTE) in patients with pancreatic cancer: Effect of timing of VTE on survival.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4037-4037
Author(s):  
Maithili A Shethia ◽  
Aparna Hegde ◽  
Xiao Zhou ◽  
Michael J. Overman ◽  
Saroj Vadhan-Raj
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Survival Analysis ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic ◽  
One Year ◽  
The Impact

4037 Background: Patients (pts) with pancreatic cancer are at high risk for VTE, and the occurrence of VTE can affect pts’ prognosis. The purpose of this study was to evaluate the incidence of VTE and the impact of timing of VTE (early vs. late) on survival. Methods: Medical record of 260 pts with pancreatic cancer, newly referred to UT MDACC during one year period from 1/1/2006 to 12/31/2006, were reviewed for the incidence of VTE during a 2-year follow-up period from the date of diagnosis. All VTE episodes were confirmed by radiologic studies. Survival analysis was conducted using Kaplan-Meier analysis and Cox proportional hazard models. Results: Of the 260 pts, 47 pts (18%) had 51 episodes of VTE during the 2-year follow-up. The median age of the pts with VTE was 61 years (range: 28-86) and 53% were males. Of the 47 pts with VTE, 27 (57%) had PE, 19 (40%) had DVT and 1 had concurrent PE/DVT. Three pts had recurrent VTE during the study period. Median follow-up time for OS was 192 days (range: 1-1652 days). Kaplan-Meier Survival analysis showed that those who developed VTE earlier (within 30 or 90 days) had shorter median overall survival (OS) compared with those who had VTE beyond these time points. The hazard ratios, 95% CI, and median OS at 1 year are summarized in the table below. Conclusions: The incidence of VTE is high in pts with pancreatic cancer. The timing of VTE had a significant impact on OS; pts who had an early development of VTE had a shorter overall survival. [Table: see text]

Low TWEAK expression indicates poor survival and is correlated with sparse TIICs in lung adenocarcinoma (LUAD).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21017-e21017
Author(s):  
Jinchun Wu ◽  
Xianyu Liu ◽  
Yanhua Mou ◽  
Shan Zeng ◽  
Jin Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Lung Adenocarcinoma ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Immune Escape ◽  
Underlying Mechanism ◽  
Memory Cd8 T Cells ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

e21017 Background: Lung adenocarcinoma (LUAD) occupies the most of non-small cell lung cancer (NSCLC) and shows promising response to PD-1 immunotherapy, but immune escape will cause treatment failure indicating poor prognosis. TWEAK (Tumor necrosis factor-related weak inducer of apoptosis, also known as TNFSF12) combining with its receptor FN14 (fibroblast growth factor–inducible 14) mediates crucial innate and adaptive immune pathways to promote the progression of multiple autoimmune diseases. So we assumed that TWEAK is a prognostic predictor and related with tumor-infiltrating immune cells (TIICs) in LUAD. Methods: TWEAK expression of LUAD was primarily investigated in The Cancer Immunome Atlas (TCIA) and then validated in Tumor Immune Estimation Resource (TIMER) databases. We assessed the effect of TWEAK on the survival via the Kaplan-Meier plotter, GEPIA2 (gene expression profiling interactive analysis) and PrognoScan databases. The relation between TWEAK and TIICs was explored in TIMER and TCIA, as well as the correlation of TWEAK and FN14 was analyzed in TIMER and GEPIA2. Results: Low TWEAK expression was significantly associated with poor relapse-free survival (RFS) (HR = 0.62, 95% CI = 0.4~0.97, logrank P = 0.035) and overall survival (OS) (HR = 0.61, 95% CI = 0.46~0.83, logrank P = 0.0012) in LUAD from Kaplan-Meier plotter. Similar impacts of TWEAK on the survival were validated in GEPIA2 and four independent cohorts from PrognoScan (jacob-00182-CANDF, GSE13213, jacob-00182-MSK and GSE31210). Moreover, reduced TWEAK expression was closely related with the paucity of TIICs which contributed to poor OS, including central memory CD8 T cells, plasmacytoid dendritic cells, activated CD8 T cells, monocytes, T follicular helper cells, immature B cells and eosinophils. In addition, TWEAK expression was positively related with the expression level of FN14 in both GEPIA2(R = 0.13, P= 0.0031) and TIMER (partial.cor = 0.212, P= 2.04e-06). Conclusions: Low TWEAK expression maybe indicate poor prognosis in LUAD, and correlated with the impaired infiltration of immune cells in the tumor region. The defective TWEAK/FN14 pathway possibly accounts for these observations, but the underlying mechanism needs to be further explored.

scholarly journals Survival for Chronic Lymphocytic Leukaemia (CLL) Patients in Hungary from 2000 to 2014 Based on the Single Payer's Database: A Nationwide Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1275-1275
Author(s):  
Maren Gaudig ◽  
István Vályi-Nagy ◽  
Peter Takacs ◽  
Miklos Bacskai ◽  
Petra Kozma ◽  
...  
Keyword(s):  
Health Care ◽  
Overall Survival ◽  
Survival Analysis ◽  
Health Insurance ◽  
Survival Probability ◽  
Outpatient Care ◽  
Lymphocytic Leukaemia ◽  
Kaplan Meier ◽  
Age Cohort ◽  
First Diagnosis

Abstract Background: Real-world evidence based analyses are gaining importance worldwide. They are especially useful to inform medical/scientific evidence setting, health policy decision-making, or health-economic modelling. Due to legislation for data of public interest set in Act LXIII of 2012, health care data recorded by the predominantly state-owned health insurance system are accessible in Hungary. The National Health Insurance Fund Administration (NHIFA) as single payer covers the total population of 10 million inhabitants, providing de-identified patient data on health care resource utilization and demographics upon request. Chronic lymphocytic leukaemia is an adult haematological malignancy. New therapies, e.g. BTKs need to find their place in therapy but the currently available information in Hungary on epidemiology, patient pathways and characteristics on population level are scarce. Aim: During the last decade numerous novel therapeutic options became available. Mortality as an important treatment outcome is of interest to understand any impact these novel agents may have. We evaluated overall survival during the period from 2000 – 2013 with the hypothesis that survival rate is strongly correlated with time of first diagnosis and subsequently availability of appropriate therapies. Methods: As part of a larger project called LYRICS (Lymphoma Real-Life Insight Core Survey) we have conducted a comprehensive retrospective analysis based on the NHIFA's database to map the CLL therapy landscape and outcomes in the last 14 years. The basis of the analysis was the claims database of inpatient and outpatient care (DRG based financing) and outpatient drug reimbursement system. Mortality rates were studied by non-parametric (Kaplan-Meier survival analysis) and semi-parametric (Cox proportional hazard regression) approaches. Results:The annual number of prevalent CLL patients is 3-4,000 with 8-900 newly diagnosed patients annually. The assessment was based on at least two relevant and confirmed C91.10 ICD diagnoses in inpatient or outpatient care. Kaplan-Meier curve estimates show the median overall survival from diagnosis is 80 months. The survival probability at one elapsed year is 91% in CLL patients diagnosed between the years 2002-2013, and 95% in the years between 2007-2013. The 4-year survival probability is 67% for patients diagnosed between the years of 2002-2013 and 78% for patients diagnosed between the years 2007-2013 (Figure 1 below). By fitting Cox model with age covariates, it can be shown that there is significant difference in relative risk (RR) of death in different age cohorts. The RR of death in the 60-69 age cohort is 1.5 times and in the 70-79 age cohort is more than 2 times higher than in the 50-59 age cohort of CLL patients. Figure 1 Survival analysis from first diagnosis by Kaplan-Meier method Figure 1. Survival analysis from first diagnosis by Kaplan-Meier method Conclusion: These results from this analyses show a significant increase of survival in Hungary over the last 15 years. The availability of treatment options have contributed to this increased survival probability. This population, real-world data confirms the relevance of age at first diagnosis as predictor for overall survival. Recently approved therapies in CLL, e.g. Ibrutinib are expected to further improve the mortality outcome for this patient group. Disclosures Gaudig: Janssen : Employment. Vályi-Nagy:Janssen-Cilag Ltd.: Consultancy. Takacs:Janssen-Cilag Ltd. Hungary: Employment. Bacskai:Healthware Consulting Ltd: Equity Ownership. Kozma:Janssen-Cilag Ltd. Hungary: Employment. Rakonczai:Healthware Consulting Ltd: Employment. Püspöki:Healthware Consulting Ltd: Employment.

scholarly journals Transcriptome analysis revealed key prognostic genes and microRNAs in hepatocellular carcinoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8930 ◽  
Author(s):  
Xi Ma ◽  
Lin Zhou ◽  
Shusen Zheng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Survival Analysis ◽  
Poor Prognosis ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Pathway Enrichment Analysis ◽  
Cox Regression Analysis ◽  
Key Genes ◽  
Overall Survival Analysis

Background Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, the molecular mechanisms involved in HCC remain unclear and are in urgent need of elucidation. Therefore, we sought to identify biomarkers in the prognosis of HCC through an integrated bioinformatics analysis. Methods Messenger RNA (mRNA) expression profiles were obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) for the screening of common differentially expressed genes (DEGs). Function and pathway enrichment analysis, protein-protein interaction network construction and key gene identification were performed. The significance of key genes in HCC was validated by overall survival analysis and immunohistochemistry. Meanwhile, based on TCGA data, prognostic microRNAs (miRNAs) were decoded using univariable and multivariable Cox regression analysis, and their target genes were predicted by miRWalk. Results Eleven hub genes (upregulated ASPM, AURKA, CCNB2, CDC20, PRC1 and TOP2A and downregulated AOX1, CAT, CYP2E1, CYP3A4 and HP) with the most interactions were considered as potential biomarkers in HCC and confirmed by overall survival analysis. Moreover, AURKA, PRC1, TOP2A, AOX1, CYP2E1, and CYP3A4 were considered candidate liver-biopsy markers for high risk of developing HCC and poor prognosis in HCC. Upregulation of hsa-mir-1269b, hsa-mir-518d, hsa-mir-548aq, hsa-mir-548f-1, and hsa-mir-6728, and downregulation of hsa-mir-139 and hsa-mir-4800 were determined to be risk factors of poor prognosis, and most of these miRNAs have strong potential to help regulate the expression of key genes. Conclusions This study undertook the first large-scale integrated bioinformatics analysis of the data from Illumina BeadArray platforms and the TCGA database. With a comprehensive analysis of transcriptional alterations, including mRNAs and miRNAs, in HCC, our study presented candidate biomarkers for the surveillance and prognosis of the disease, and also identified novel therapeutic targets at the molecular and pathway levels.

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