Bioinformatics Analysis of The Expression of ATP Binding Cassette Transporters and The Screening of Regulatory Genes in PTEN/PI3K/Akt/mTOR Signaling Pathway in The Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Tingdan Zheng ◽  
Wuqi Song ◽  
Aiying Yang
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Bioinformatics Analysis ◽  
Wilcoxon Test ◽  
Rank Test ◽  
Short Term ◽  
Term Survival ◽  
Log Rank Test ◽  
Short Term Survival

Abstract Objective Here we performed the Bioinformatics analysis on the data from The Cancer Genome Atlas (TCGA), in order to find the correlation between the expression of ATP Binding Cassette (ABC) Transporters’ genes and hepatocellular carcinoma (HCC) prognosis; Methods Transcriptome profiles and clinical data of HCC were obtained from TCGA database. Package edgeR was used to analyze differential gene expression. Patients were divided into low-ABC expression and high-ABC expression groups based on the median expression level of ABC genes in cancer. The overall survival and short-term survival (n= 341) of the two groups was analyzed using the log-rank test and Wilcoxon test; Results We found that ABC gene expression was correlated with the expression of PIK3C2B (p<0.001, ABCC1: r=0.27; ABCC10: r=0.57; ABCC4: r=0.20; ABCC5: r=0.28; ABCB9: r=0.17; ABCD1: r=0.21). All patients with low-ABC expression showed significantly increased overall survival. Significantly decreased overall survival (Log-rank test: p<0.05, Wilcoxon test: p<0.05) was found in patients with high expression of ABCC1 (HR=1.58), ABCD1 (HR=1.45), ABCC4 (HR=1.56), and ABCC5 (HR=1.64), while decreased short-term survival (Log-rank test: p>0.05, Wilcoxon test: p<0.05) was correlated with the increased expression of ABCC10 (HR=1.29), PIK3C2B (HR=1.29) and ABCB9 (HR=1.23); Conclusions Our findings indicate that the specific ABC gene expression correlates with the prognosis of HCC. Therefore, ABC expression profile could be a potential indicator for HCC patients.

scholarly journals Anesthetics and long-term survival after cancer surgery—total intravenous versus volatile anesthesia: a retrospective study

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Boohwi Hong ◽  
Sunyeul Lee ◽  
Yeojung Kim ◽  
Minhee Lee ◽  
Ann Misun Youn ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Cancer Surgery ◽  
Trial Registration ◽  
Favorable Effect ◽  
Rank Test ◽  
Intravenous Anesthesia ◽  
Term Survival ◽  
Log Rank Test ◽  
Number Of Patients

Abstract Background Intravenous anesthesia has been reported to have a favorable effect on the prognosis of cancer patients. This study was performed to analyze data regarding the relation between anesthetics and the prognosis of cancer patients in our hospital. Methods The medical records of patients who underwent surgical resection for gastric, lung, liver, colon, and breast cancer between January 2006 and December 2009 were reviewed. Depending on the type of anesthetic, it was divided into total intravenous anesthesia (TIVA) or volatile inhaled anesthesia (VIA) group. The 5-year overall survival outcomes were analyzed by log-rank test. Cox proportional hazards modeling was used for sensitivity. Results The number of patients finally included in the comparison after propensity matching came to 729 in each group. The number of surviving patients at 5 years came to 660 (90.5%) in the TIVA and 673 (92.3%) in the VIA. The type of anesthetic did not affect the 5-year survival rate according to the log-rank test (P = 0.21). Variables associated with a significant increase in the hazard of death after multivariable analysis were male sex and metastasis at surgery. Conclusions There were no differences in 5-year overall survival between two groups in the cancer surgery. Trial registration Trial registration: CRIS KCT0004101. Retrospectively registered 28 June 2019.

Combining Proteomics and Gene Expression Profiling Identifies Proteins/Genes Associated with Short Overall Survival in Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 197-197
Author(s):  
Ricky D Edmondson ◽  
Shweta S. Chavan ◽  
Christoph Heuck ◽  
Bart Barlogie
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Multivariate Analyses ◽  
Rank Test ◽  
P Value ◽  
Newly Diagnosed ◽  
Training Set ◽  
Test Set ◽  
Log Rank Test ◽  
Test Sets

Abstract Abstract 197 We and others have used gene expression profiling to classify multiple myeloma into high and low risk groups; here, we report the first combined GEP and proteomics study of a large number of baseline samples (n=85) of highly enriched tumor cells from patients with newly diagnosed myeloma. Peptide expression levels from MS data on CD138-selected plasma cells from a discovery set of 85 patients with newly diagnosed myeloma were used to identify proteins that were linked to short survival (OS < 3 years vs OS ≥ 3 years). The proteomics dataset consisted of intensity values for 11,006 peptides (representing 2,155 proteins), where intensity is the quantitative measure of peptide abundance; Peptide intensities were normalized by Z score transformation and significance analysis of microarray (SAM) was applied resulting in the identification 24 peptides as differentially expressed between the two groups (OS < 3 years vs OS ≥ 3 years), with fold change ≥1.5 and FDR <5%. The 24 peptides mapped to 19 unique proteins, and all were present at higher levels in the group with shorter overall survival than in the group with longer overall survival. An independent SAM analysis with parameters identical to the proteomics analysis (fold change ≥1.5; FDR <5%) was performed with the Affymetrix U133Plus2 microarray chip based expression data. This analysis identified 151 probe sets that were differentially expressed between the two groups; 144 probe sets were present at higher levels and seven at lower levels in the group with shorter overall survival. Comparing the SAM analyses of proteomics and GEP data, we identified nine probe sets, corresponding to seven genes, with increased levels of both protein and mRNA in the short lived group. In order to validate these findings from the discovery experiment we used GEP data from a randomized subset of the TT3 patient population as a training set for determining the optimal cut-points for each of the nine probe sets. Thus, TT3 population was randomized into two sub-populations for the training set (two-thirds of the population; n=294) and test set (one-third of the population; n=147); the Total Therapy 2 (TT2) patient population was used as an additional test set (n=441). A running log rank test was performed on the training set for each of the nine probe sets to determine its optimal gene expression cut-point. The cut-points derived from the training set were then applied to TT3 and TT2 test sets to investigate survival differences for the groups separated by the optimal cutpoint for each probe. The overall survival of the groups was visualized using the method of Kaplan and Meier, and a P-value was calculated (based on log-rank test) to determine whether there was a statistically significant difference in survival between the two groups (P ≤0.05). We performed univariate regression analysis using Cox proportional hazard model with the nine probe sets as variables on the TT3 test set. To identify which of the genes corresponding to these nine probes had an independent prognostic value, we performed a multivariate stepwise Cox regression analysis. wherein CACYBP, FABP5, and IQGAP2 retained significance after competing with the remaining probe sets in the analysis. CACYBP had the highest hazard ratio (HR 2.70, P-value 0.01). We then performed the univariate and multivariate analyses on the TT2 test set where CACYBP, CORO1A, ENO1, and STMN1 were selected by the multivariate analysis, and CACYBP had the highest hazard ratio (HR 1.93, P-value 0.004). CACYBP was the only gene selected by multivariate analyses of both test sets. Disclosures: No relevant conflicts of interest to declare.

Center Experience and Calendar Year Of Transplantation Strongly Influence Short Term Survival After Autologous Peripheral Blood Transplantation In 1315 Patients With Light Chain Amyloidosis: An EBMT Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 417-417
Author(s):  
Stefan O Schonland ◽  
Ute Hegenbart ◽  
Simona Iacobelli ◽  
Jennifer Hoek ◽  
M Rovira ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Performance Status ◽  
Rank Test ◽  
High Dose ◽  
Al Amyloidosis ◽  
Advisory Committees ◽  
Term Survival ◽  
Log Rank Test ◽  
One Year ◽  
Short Term Survival

Abstract Introduction High-dose chemotherapy and autologous stem cell transplantation (ASCT) is a treatment option for eligible patients with systemic light chain (AL) amyloidosis. Compared to patients with multiple myeloma (MM), the risk for complications and transplant-related mortality is increased. However, in this fragile patient group it is often not possible to distinguish between treatment- and amyloidosis-related deaths in the post-transplant period. The CIBMTR reported a one year survival (1-yr OS) of 66% of patients transplanted between 1995 and 2001. Another multicenter analysis from Great Britain reported a one year survival of 75% (Goodman et al., BJH, 2006); interestingly, they could show a significant reduction of day 100 all-cause mortality from 32% to 13% after 1998. In recent single center studies 1-yr OS was better ranging from 80% to 90% (reviewed by Schönland et al., BMT, 2011). The amyloidosis groups of Mayo Clinic and Boston Medical School could also show a survival improvement over time (Tsai et al., Blood, 2012 and Gertz et al., BMT, 2010). Specific Aim The aim of this retrospective study was to analyze the 1-yr OS after ASCT for patients with AL amyloidosis in Europe. Of special interest were calendar year of transplants and center experience. Methodology Patient-, disease-, and transplant-related variables were collected according to the data entries in the EBMT database. Inclusion criteria were as follows: first autologous transplant with peripheral blood stem cells performed between 1997 and 2010. Center experience was measured for each patient by the number of previous MM ASCT done in the center until the year of AL transplant. Results 1315 patients from 259 centers fulfilled the entry criteria and were included in the analysis (for patient characteristics see table). The conditioning regimen was high-dose melphalan in most cases. Median follow up was 47 months. 1-yr OS after ASCT was 80.7% (CI 78.5 – 82.9). In univariate analysis age, gender, time from diagnosis to ASCT had no influence on 1-yr OS. Bad performance status (57% (50-65) vs. 90% (87-92); p<0.001) and progression/relapse as status at conditioning (61% (53-69) vs. 85% (83-87); p<0.001) significantly reduced 1-yr OS. A strong and significant influence of the transplant period (see figure 1, log-rank test, p<0.001) and higher center experience (see figure 2; log-rank test, p<0.001) could also be demonstrated. Interestingly, the proportion of patients with bad performance status decreased from 28% to 13% in most recent years (p=0.001). These results hold in multivariate analysis. Bad performance status (HR 4.3; p<0.001), progression/relapse as status at conditioning (HR 1.96; p<0.001) and earlier transplant period (HR 1.1; p<0.001) retained their highly significant negative influence on 1-yr OS. In an alternative multivariate model replacing transplant period with center experience, the latter has also a beneficial effect (HR 0.99 for 10 additional previous MM transplants; p=0.015) and all other prognostic factors retained the estimated effects. Conclusion This is the first report from the EBMT about the results of ASCT in AL amyloidosis from 259 European centers and the largest retrospective analysis for this rare entity. It clearly shows that short term survival has been improved over time probably due to better patient selection and increase of center experience. Of note, in the most recent cohort (2009 to 2010) the 1-yr OS was 91% (CI 87-96) supporting the further use of ASCT in eligible AL amyloidosis patients. Disclosures: Leblond: Roche : Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Mundipharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau.

N-cadherin, E-cadherin, ERCC1, and c-kit expression in small cell lung cancer (SCLC) and potential for new therapeutic targets

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22157-e22157
Author(s):  
M. Batus ◽  
R. Myint ◽  
J. Coon ◽  
S. Basu ◽  
K. Kaiser ◽  
...  
Keyword(s):  
Overall Survival ◽  
Molecular Markers ◽  
Performance Status ◽  
Prognostic Significance ◽  
Wilcoxon Test ◽  
Rank Test ◽  
Clinical Activity ◽  
Log Rank Test ◽  
Treatment Type ◽  
E Cadherin

e22157 Background: Minimal advances have been made in the treatment of SCLC. Molecular markers may allow us to better stratify patients (pts) for new treatment options and drug combinations. The objective of our study was to determine the frequency and potential prognostic significance of N-cadherin (N-cad), E-cadherin (E-cad), ERCC1, and c-kit (CD117) expression in SCLC. Methods: Tissue from 132 pts with SCLC was retrospectively stained for N-cad, E-cad, ERCC1, and c-kit. Frequency of expression (% of tumor cells staining positive) was measured on a scale of 0–4 (freq 0=no expression (<1%), freq 1=1–10%, freq 2=11–35%, freq 3=36–70%, freq 4=71–100%). Charts were reviewed for stage, performance status, date of diagnosis/death, survival, and treatment (type, dates, response). The frequency of molecular markers was correlated with clinical data and overall survival. Results: Age range 42 to 97 years, 65 male:67 female, and 64 had limited and 68 had extensive stage. Of the 132 pts, 75% had tumors that expressed (frequency ≥ 1) N-cad, 58% E-cad, 70% ERCC1, and 55% c-kit. Comparing tumor marker expression with survival using either the Log-Rank Test or the Wilcoxon Test, there was no significant association for N-cad, E-cad, or ERCC1. However, tumors that expressed c-kit with frequency ≥ 3 had a trend toward superior survival compared with frequency < 3. Median survival for c-kit frequency ≥ 3 was 496 days compared to 312 days for frequency < 3 (p = 0.09, Log-Rank Test). Conclusions: In our retrospective study of 132 SCLC pts, we found that all 4 markers were expressed in greater than 50% of specimens, and that higher c-kit expression was associated with marginally significant increase in overall survival. Though previous experience with imatinib alone or with chemotherapy showed limited clinical activity in unselected SCLC pts, given preclinical synergy with cisplatin, it seems reasonable to consider combination therapy with cisplatin/etoposide and imatinib in pts selected for high c-kit expression. [Table: see text] No significant financial relationships to disclose.

scholarly journals Identification of an eight-gene signature for survival prediction for patients with hepatocellular carcinoma based on integrated bioinformatics analysis

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6548 ◽  
Author(s):  
Guo-jie Qiao ◽  
Liang Chen ◽  
Jin-cai Wu ◽  
Zhou-ri Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Bioinformatics Analysis ◽  
Gene Signature ◽  
Training Dataset ◽  
Rank Test ◽  
Survival Prediction ◽  
Gene Model ◽  
Cox Regression Analysis ◽  
Log Rank Test

Background Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related death worldwide. Despite recent advances in imaging techniques and therapeutic intervention for HCC, the low overall 5-year survival rate of HCC patients remains unsatisfactory. This study aims to find a gene signature to predict clinical outcomes in HCC. Methods Bioinformatics analysis including Cox’s regression analysis, Kaplan-Meier (KM) and receiver operating characteristic curve (ROC) analysis and the random survival forest algorithm were performed to mine the expression profiles of 553 hepatocellular carcinoma (HCC) patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public database. Results We selected a signature comprising eight protein-coding genes (DCAF13, FAM163A, GPR18, LRP10, PVRIG, S100A9, SGCB, and TNNI3K) in the training dataset (AUC = 0.77 at five years, n = 332). The signature stratified patients into high- and low-risk groups with significantly different survival in the training dataset (median 2.20 vs. 8.93 years, log-rank test P < 0.001) and in the test dataset (median 2.68 vs. 4.24 years, log-rank test P = 0.004, n = 221, GSE14520). Further multivariate Cox regression analysis showed that the signature was an independent prognostic factor for patients with HCC. Compared with TNM stage and another reported three-gene model, the signature displayed improved survival prediction power in entire dataset (AUC signature = 0.66 vs. AUC TNM = 0.64 vs. AUC gene model = 0.60, n = 553). Stratification analysis shows that it can be used as an auxiliary marker for many traditional staging models. Conclusions We constructed an eight-gene signature that can be a novel prognostic marker to predict the survival of HCC patients.

Dose-survival relationship in patients with hepatocellular carcinoma undergoing stereotactic body radiation therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15592-e15592
Author(s):  
Ting-Shi Su ◽  
Shi-Xiong Liang ◽  
Lequn Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Stereotactic Body Radiation Therapy ◽  
Liver Volume ◽  
Rank Test ◽  
Stereotactic Ablative Radiotherapy ◽  
Term Survival ◽  
Stereotactic Body Radiation ◽  
Dosing Regimens

e15592 Background: Stereotactic body radiation therapy (SBRT) has become a treatment for hepatocellular carcinoma (HCC) from palliative to radical treatment. But there is no clear evidence of a dose-survival relationship among commonly-utilized radiation therapy schedules. We aimed to determine the comparative effectiveness of different SBRT dosing regimens for HCC. Methods: The dataset collected from Guangxi Zhuang Autonomous Region in China was used. In this large single-centered retrospective study, 604 patients treated with SBRT were included from 2011 to 2017. Biologically effective dose (BED10) and equivalent dose in 2 Gy fractions (EQD2) were assumed at an α/β ratio of 10. Overall survival (OS) was the primary endpoint. OS rates were estimated using Kaplan–Meier curves with a log-rank test. Results: The median tumor size was 5.2 cm (interquartile range [IQR], 1.1–21.0 cm). Median follow-up was 21 months in surviving patients (IQR, 3–82 months). The 1-, 3-, and 5-year OSs were 87.1%, 64.7%, and 60.9% in Barcelona Clinic Liver Cancer (BCLC)-A group; 72.9%, 37.2%, and 30.7% in BCLC-B group; and 44.3%, 18.6%, and 12.8% in BCLC-C group; respectively. Increasing the RT dose was associated with improved overall survival. Stereotactic ablative radiotherapy (SART) with BED10≥100 Gy, SBRT with EQD2≥74 Gy and BED10 < 100 Gy, and stereotactic conservative radiotherapy (SCRT) with EQD2< 74 Gy have 3 separate curves for long-term survival post-SBRT. On multivariate analysis, Clinical factors associated with improved OS were BED, alanine aminotransferase (ALT) , and BCLC stage. On the subgroup analysis, BED10 ≥100 Gy was still beneficial against HCCs of BCLC stage A, B, and C. Conclusions: Individualized dose for SBRT are recommended for the treatment of HCC due to different degrees of cirrhosis and liver volume. The RT dose was classified into three levels. If tolerated by normal tissue, SART with BED10 ≥100 Gy as a first-line ablative dose or SBRT with EQD2 ≥74 Gy as a second-line radical dose is recommended. Otherwise, SCRT with EQD2< 74 Gy is recommended as palliative irradiation.

scholarly journals Safety and effectiveness of multi-antenna microwave ablation-oriented combined therapy for large hepatocellular carcinoma

2019 ◽  
Vol 12 ◽  
pp. 175628481986296 ◽  
Author(s):  
Tian-qi Zhang ◽  
Zhi-mei Huang ◽  
Jing-xian Shen ◽  
Gui-qun Chen ◽  
Lu-jun Shen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Local Control ◽  
Microwave Ablation ◽  
Tumor Necrosis ◽  
Combined Therapy ◽  
Survival Rates ◽  
Treatment Protocol ◽  
Short Term ◽  
Term Survival ◽  
Short Term Survival

Background: In patients with a large, unresectable hepatocellular carcinoma (HCC), the primary recommendation is for transarterial chemoembolization (TACE) but used alone TACE is not typically curative. Combinations of TACE followed in a delayed fashion by single-applicator thermal ablation have also been suboptimal. As an alternative, we investigated the combination of TACE followed within 1–3 days by multi-antenna microwave ablation (MWA) in patients with a large HCC, to determine the feasibility, safety, local control, and short-term survival rates of this approach. Methods: We retrospectively studied 43 patients with a large HCC (mean diameter, 8.8 cm; SD, 2.8 cm) treated between July 2015 and July 2018, who underwent TACE followed within 3 days by multi-antenna simultaneous MWA. We measured the liver and renal function before and after treatment, recorded complications, used three-dimensional software and imaging to calculate tumor necrosis rates at 1 month after therapy, and calculated overall survival (OS) and progression-free survival (PFS) using the Kaplan–Meier method. Results: Mean follow up was 12.2 (range, 3.5–35.6) months. All patients completed the treatment protocol. At 1 month after combined therapy, tumor necrosis was complete in 16 (37.2%), nearly complete in 19 (44.2%), and partial in 8 (18.6%) patients. The 1- and 2-year OS rates were 64.0% and 46.8%, respectively, with a median OS of 23.0 months; and the 1- and 2-year PFS rates were 19.9% and 4.4%, respectively, with a median PFS of 4.2 months. A transient change in liver function occurred 3 days after MWA but resolved within 1 month. Only two patients had major complications, which were treatable and resolved. Conclusion: Multi-antenna MWA-oriented combined therapy is feasible and well tolerated, and it results in satisfactory initial local control and short-term survival in some but not all patients with a large HCC.

scholarly journals Transarterial Chemoembolization of Hepatocellular Carcinoma with Oncozene Microspheres: An Initial, Short-Term Clinical Experience—A Retrospective, Matched, Comparison Study

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 600
Author(s):  
Matthew L. Hung ◽  
Jerry Jiang ◽  
Harry Trieu ◽  
Frank Hao ◽  
Navid Eghbalieh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Transarterial Chemoembolization ◽  
Tumor Response ◽  
Progression Free Survival ◽  
Embolic Agent ◽  
Rank Test ◽  
Fisher Exact Test ◽  
Short Term ◽  
Free Survival

Background: The purpose of this study is to describe a single institution’s experience using Oncozene (OZ) microspheres for transarterial chemoembolization (OZ-TACE) of hepatocellular carcinoma (HCC), and to compare tolerability, safety, short-term radiographic tumor response, progression-free survival (PFS), and overall survival (OS) of these procedures to TACE (LC-TACE) performed with LC beads (LC). Methods: A retrospective, matched cohort study of patients undergoing DEB-TACE (drug-eluting bead transarterial chemoembolization) with OZ or LC was performed. The cohort comprised 23 patients undergoing 29 TACE with 75 or 100 μm OZ and 24 patients undergoing 29 TACE with 100–300 μm LC. Outcome measures were changes in liver function tests, complications, treatment tolerability, short-term radiographic tumor response according to modified RECIST criteria for HCC, PFS, and 1-year OS. The Mann–Whitney U test, Fisher exact test, and log rank test were used to compare the groups. Results: The BCLC or Child–Pugh scores were similar between the OZ and LC group. However, the two groups differed with respect to the etiology of background cirrhosis (p = 0.02). All other initial demographic and tumor characteristics were similar between the two groups. OZ-TACE used less doxorubicin per treatment compared to LC-TACE (median 50 vs. 75 mg; p = 0.0005). Rates of pain, nausea, and postembolization syndrome were similar, irrespective of the embolic agent used. OZ-TACE resulted in an overall complication rate comparable to LC-TACE (20.7% vs. 10.3%; p = 0.47). LC-TACE resulted in a higher percent increase in total bilirubin on post-procedure day 1 (median 18.8 vs. 0%; p = 0.05), but this difference resolved at 1 month. Both OZ-TACE and LC-TACE resulted in similar complete (31% vs. 24%) and objective (66% vs. 79%) target lesion response rates on 1-month post-TACE imaging. Both OZ-TACE and LC-TACE had similar median progression-free survival (283 vs. 209 days; p = 0.14) and 1-year overall survival rates (85% vs. 76%; p = 0.30). Conclusion: With a significantly reduced dose of doxorubicin, TACE performed with Oncozene microspheres in a heterogeneous patient population is well-tolerated, safe, and produces a similar radiological response and survival rate when compared to LC Bead TACE.

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