scholarly journals Identification of Arp2/3 Complex Subunits as Prognostic Biomarkers for Hepatocellular Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Shenglan Huang ◽  
Dan Li ◽  
LingLing Zhuang ◽  
Liying Sun ◽  
Jianbing Wu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Expression ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Biomarkers ◽  
Migration And Invasion ◽  
Regression Analyses ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

The actin-related protein 2/3 complex (Arp2/3) is a major actin nucleator that has been widely reported and plays an important role in promoting the migration and invasion of various cancers. However, the expression patterns and prognostic values of Arp2/3 subunits in hepatocellular carcinoma (HCC) remain unclear. In this study, The Cancer Genome Atlas (TCGA) and UCSC Xena databases were used to obtain mRNA expression and the corresponding clinical information, respectively. The differential expression and Arp2/3 subunits in HCC were analyzed using the “limma” package of R 4.0.4 software. The prognostic value of each subunit was evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression analyses. The results revealed that mRNA expression of Arp2/3 members (ACTR2, ACTR3, ARPC1A, APRC1B, ARPC2, ARPC3, ARPC4, ARPC5, and ARPC5L) was upregulated in HCC. Higher expression of Arp2/3 members was significantly correlated with worse overall survival (OS) and shorter progression-free survival (PFS) in HCC patients. Cox proportional hazards regression analyses demonstrated that ACTR3, ARPC2, and ARPC5 were independent prognostic biomarkers of survival in patients with HCC. The relation between tumor immunocyte infiltration and the prognostic subunits was determined using the TIMER 2.0 platform and the GEPIA database. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms of prognostic subunits in the carcinogenesis of HCC. The results revealed that ACTR3, ARPC2, and ARPC5 were significantly positively correlated with the infiltration of immune cells in HCC. The GSEA results indicated that ACTR3, ARPC2, and ARPC5 are involved in multiple cancer-related pathways that promote the development of HCC. In brief, various analyses indicated that Arp2/3 complex subunits were significantly upregulated and predicted worse survival in HCC, and they found that ACTR3, ARPC2, and ARPC5 could be used as independent predictors of survival and might be applied as promising molecular targets for diagnosis and therapy of HCC in the future.

scholarly journals A novel long non-coding RNA, AC012456.4, as a valuable and independent prognostic biomarker of survival in oral squamous cell carcinoma

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5307 ◽  
Author(s):  
Xuegang Hu ◽  
Zailing Qiu ◽  
Jianchai Zeng ◽  
Tingting Xiao ◽  
Zhihong Ke ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Survival Analysis ◽  
Oral Squamous Cell Carcinoma ◽  
Proportional Hazards ◽  
Prognostic Biomarker ◽  
Cox Proportional Hazards ◽  
Regression Analyses ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Kaplan Meier

Oral squamous cell carcinoma (OSCC) is a major malignant cancer of the head and neck. Long non-coding RNAs (lncRNAs) have emerged as critical regulators during the development and progression of cancers. This study aimed to identify a lncRNA-related signature with prognostic value for evaluating survival outcomes and to explore the underlying molecular mechanisms of OSCC. Associations between overall survival (OS), disease-free survival (DFS) and candidate lncRNAs were evaluated by Kaplan–Meier survival analysis and univariate and multivariate Cox proportional hazards regression analyses. The robustness of the prognostic significance was shown via the Gene Expression Omnibus (GEO) database. A total of 2,493 lncRNAs were differentially expressed between OSCC and control samples (fold change >2, p < 0.05). We used Kaplan–Meier survival analysis to identify 21 lncRNAs for which the expression levels were associated with OS and DFS of OSCC patients (p < 0.05) and found that down-expression of lncRNA AC012456.4 especially contributed to poor DFS (p = 0.00828) and OS (p = 0.00987). Furthermore, decreased expression of AC012456.4 was identified as an independent prognostic risk factor through multivariate Cox proportional hazards regression analyses (DFS: p = 0.004, hazard ratio (HR) = 0.600, 95% confidence interval(CI) [0.423–0.851]; OS: p = 0.002, HR = 0.672, 95% CI [0.523–0.863). Gene Set Enrichment Analysis (GSEA) indicated that lncRNA AC012456.4 were significantly enriched in critical biological functions and pathways and was correlated with tumorigenesis, such as regulation of cell activation, and the JAK-STAT and MAPK signal pathway. Overall, these findings were the first to evidence that AC012456.4 may be an important novel molecular target with great clinical value as a diagnostic, therapeutic and prognostic biomarker for OSCC patients.

scholarly journals Replacement of potatoes with other vegetables and risk of myocardial infarction in the Danish Diet, Cancer and Health cohort

2021 ◽  
pp. 1-21
Author(s):  
Anne Mette L. Würtz ◽  
Mette D. Hansen ◽  
Anne Tjønneland ◽  
Eric B. Rimm ◽  
Erik B. Schmidt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Similar Pattern ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Heterogeneous Group ◽  
Dietary Guidelines ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Root Vegetables

ABSTRACT Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29,142 women and 26,029 men aged 50-64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazards ratios (HR) with 95% CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13.6 years of follow-up, 656 female and 1,694 male cases were identified. Among women, the adjusted HR for MI was 1.02 (95% CI: 0.93, 1.13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0.93 (95% CI: 0.77, 1.13) for replacement of potatoes with fruiting vegetables and 0.91 (95% CI: 0.77, 1.07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.

scholarly journals Cyclin B1 acts as a tumor microenvironment-related cancer promoter and prognostic biomarker in hepatocellular carcinoma

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110162
Author(s):  
Yangming Hou ◽  
Xin Wang ◽  
Junwei Wang ◽  
Xuemei Sun ◽  
Xinbo Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Proportional Hazards ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Cyclin B1 ◽  
Cox Proportional Hazards ◽  
Gene Set Enrichment Analysis ◽  
Tumor Promoter ◽  
Protein Protein Interaction

Objectives The present study aimed to develop a gene signature based on the ESTIMATE algorithm in hepatocellular carcinoma (HCC) and explore possible cancer promoters. Methods The ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cells (TICs) in a cohort of HCC patients. The differentially expressed genes (DEGs) were screened by Cox proportional hazards regression analysis and protein–protein interaction (PPI) network construction. Cyclin B1 (CCNB1) function was verified using experiments. Results The stromal and immune scores were associated with clinicopathological factors and recurrence-free survival (RFS) in HCC patients. In total, 546 DEGs were up-regulated in low score groups, 127 of which were associated with RFS. CCNB1 was regarded as the most predictive factor closely related to prognosis of HCC and could be a cancer promoter. Gene Set Enrichment Analysis (GSEA) and CIBERSORT analyses indicated that CCNB1 levels influenced HCC tumor microenvironment (TME) immune activity. Conclusions The ESTIMATE signature can be used as a prognosis tool in HCC. CCNB1 is a tumor promoter and contributes to TME status conversion.

Development and Validation of a Prognostic Nomogram Model for Recurrence of Non-Muscle Invasive Bladder Cancer

2021 ◽  
Author(s):  
Sanhe Liu ◽  
Yongzhi Li ◽  
Diansheng Cui ◽  
Yuexia Jiao ◽  
Liqun Duan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Muscle Invasive Bladder Cancer ◽  
Clinicopathologic Characteristics ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Muscle Invasive

Abstract BackgroundDifferent recurrence probability of non-muscle invasive bladder cancer (NMIBC) requests different adjuvant treatments and follow-up strategies. However, there is no simple, intuitive, and generally accepted clinical recurrence predictive model available for NMIBC. This study aims to construct a predictive model for the recurrence of NMIBC based on demographics and clinicopathologic characteristics from two independent centers. MethodsDemographics and clinicopathologic characteristics of 511 patients with NMIBC were retrospectively collected. Recurrence free survival (RFS) was estimated using the Kaplan-Meier method and log-rank tests. Univariate Cox proportional hazards regression analysis was used to screen variables associated with RFS, and a multivariate Cox proportional hazards regression model with a stepwise procedure was used to identify those factors of significance. A final nomogram model was built using the multivariable Cox method. The performance of the nomogram model was evaluated with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed with bootstrap resampling. X-tile software was used for risk stratification calculated by the nomogram model. ResultsIndependent prognostic factors including tumor stage, recurrence status, and European Association of Urology (EAU) risk stratification group were introduced to the nomogram model. The model showed acceptable calibration and discrimination (area under the receiver operating characteristic [ROC] curve was 0.85; the consistency index [C-index] was 0.79 [95% CI: 0.76 to 0.82]), which was superior to the EAU risk stratification group alone. The decision curve also proved well clinical usefulness. Moreover, all populations could be stratified into three distinct risk groups by the nomogram model. ConclusionsWe established and validated a novel nomogram model that can provide individual prediction of RFS for patients with NMIBC. This intuitively prognostic nomogram model may help clinicians in postoperative treatment and follow-up decision-making.

Antibiotic and acid-suppression medications during early childhood are associated with obesity

Gut ◽  
2018 ◽  
Vol 68 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Christopher M Stark ◽  
Apryl Susi ◽  
Jill Emerick ◽  
Cade M Nylund
Keyword(s):  
Early Childhood ◽  
Department Of Defense ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Event Analysis ◽  
Early Exposure ◽  
Single Event ◽  
Inclusion Criteria ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

ObjectiveGut microbiota alterations are associated with obesity. Early exposure to medications, including acid suppressants and antibiotics, can alter gut biota and may increase the likelihood of developing obesity. We investigated the association of antibiotic, histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) prescriptions during early childhood with a diagnosis of obesity.DesignWe performed a cohort study of US Department of Defense TRICARE beneficiaries born from October 2006 to September 2013. Exposures were defined as having any dispensed prescription for antibiotic, H2RA or PPI medications in the first 2 years of life. A single event analysis of obesity was performed using Cox proportional hazards regression.Results333 353 children met inclusion criteria, with 241 502 (72.4%) children prescribed an antibiotic, 39 488 (11.8%) an H2RA and 11 089 (3.3%) a PPI. Antibiotic prescriptions were associated with obesity (HR 1.26; 95% CI 1.23 to 1.28). This association persisted regardless of antibiotic class and strengthened with each additional class of antibiotic prescribed. H2RA and PPI prescriptions were also associated with obesity, with a stronger association for each 30-day supply prescribed. The HR increased commensurately with exposure to each additional medication group prescribed.ConclusionsAntibiotics, acid suppressants and the combination of multiple medications in the first 2 years of life are associated with a diagnosis of childhood obesity. Microbiota-altering medications administered in early childhood may influence weight gain.

scholarly journals Prognostic value of the ALBI grade among patients with single hepatocellular carcinoma without macrovascular invasion

2020 ◽  
Author(s):  
Heng Zou ◽  
Wenhao Chen ◽  
Huan Wang ◽  
Li Xiong ◽  
Yu Wen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Size ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Grading System ◽  
Term Survival ◽  
Proportional Hazards Regression ◽  
Disease Outcomes ◽  
Single Tumor

Abstract Overview and objective: Although evidence for the application of albumin–bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Methods: Here, we enrolled patients who underwent hepatectomy due to single HCC from the year 2010 to 2014. Analyses were performed to test the potential of ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.Results: Overall, 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤ 7 cm was remarkably higher compared to those whose tumors were > 7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of the OS. The ALBI grade could stratify the patients who had a single tumor ≤ 7 cm into two distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor > 7 cm.Conclusions: We show that ALBI grading system can predict disease outcomes of single HCC patients with tumor size ≤ 7 cm. However, the ALBI grade may not predict capability the prognosis of patients with single tumor > 7 cm.

Serum FGF21 Is Associated with Future Cardiovascular Events in Patients with Coronary Artery Disease

Cardiology ◽  
2018 ◽  
Vol 139 (4) ◽  
pp. 212-218 ◽  
Author(s):  
Yun Shen ◽  
Xueli Zhang ◽  
Yiting Xu ◽  
Qin Xiong ◽  
Zhigang Lu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Regression Analysis ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Artery Disease

Objectives: To investigate whether serum fibroblast growth factor 21 (FGF21) levels can be used to predict the future development of major adverse cardiovascular events (MACEs). Methods: This study included 253 patients who received subsequent follow-up, and complete data were collected for 234 patients. Independent predictors of MACEs were identified by using the Cox proportional-hazards regression analysis. The prognostic value of FGF21 levels for MACEs was evaluated by Kaplan-Meier survival analysis. Results: Of 229 patients finally enrolled in the analysis, 27/60 without coronary artery disease (CAD) at baseline experienced a MACE, and 132/169 patients with CAD at baseline experienced a MACE. Among patients with CAD at baseline, serum FGF21 levels were significantly higher in patients with MACEs (p < 0.05) than in patients without MACEs. Kaplan-Meier survival analysis showed patients with a higher serum FGF21 had a significantly lower event-free survival (p = 0.001) than those with a lower level. Further Cox proportional-hazards regression analysis, including the traditional risk factors for cardiovascular disease, showed that serum FGF21 was an independent predictor of MACE occurrence. Conclusions: In patients with CAD at baseline, an elevated serum FGF21 level was associated with the development of a MACE in the future.

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