scholarly journals Genetic Polymorphisms in CD35 Gene Contribute to the Susceptibility and Prognosis of Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Limei Luo ◽  
Qin Li ◽  
Zhenzhen Su ◽  
Lixin Li ◽  
Bei Cai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Postoperative Recurrence ◽  
Proportional Hazard ◽  
Chinese Han ◽  
Tag Snps ◽  
Flight Mass Spectrometry ◽  
Cox Proportional Hazard ◽  
Significant Independent Risk Factor ◽  
Gene Environment ◽  
The Relationship

CD35, an important molecule implicated in inflammation and immunity, is reportedly associated with several cancers. However, very few studies have investigated the relationship between CD35 polymorphisms and hepatocellular carcinoma (HCC). The current study was conducted to investigate the association between tag SNPs in CD35 and HCC susceptibility and postoperative recurrence, in an attempt to elucidate the gene-environment interactions in HCC. A total of 1233 Chinese Han people, including 647 healthy controls and 586 HCC cases, were sampled in this study. Six Tag SNPs (rs10494885, rs2296160, rs3737002, rs3849266, rs669117, and rs7525160) of CD35 were selected using the HaploView 4.2 program and genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Overall, the mutation genotypes CC/CG of CD35 rs7525160 significantly increased the risk of HCC. Stratification analysis indicated that CD35 rs7525160 CC/CG genotypes increased HCC risk in patients younger than 65 years and were closely related to the pathological type of poor prognosis of HCC. Cox proportional hazard ratio model analysis revealed that the rs7525160 CC/CG genotype remains a significant independent risk factor for postoperative recurrence of HCC. In conclusion, CD35 rs7525160 polymorphism may contribute to the susceptibility and prognosis of HCC in the Chinese Han population.

scholarly journals Genetic Polymorphisms in CD35 Gene Contribute to the Susceptibility and Prognosis of Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Li-Mei Luo ◽  
Qin Li ◽  
Zhen-Zhen Su ◽  
Li-Xin Li ◽  
Bei Cai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Postoperative Recurrence ◽  
Proportional Hazard ◽  
Chinese Han ◽  
Tag Snps ◽  
Flight Mass Spectrometry ◽  
Cox Proportional Hazard ◽  
Significant Independent Risk Factor ◽  
Gene Environment ◽  
The Relationship

Abstract CD35, an important molecule implicated in inflammation and immunity, has been reported to contribute to several cancers. However, very few studies have investigated the relationship between CD35 polymorphisms and hepatocellular carcinoma (HCC). This study was conducted to investigate the association of tag SNPs in CD35 gene with HCC susceptibility and postoperative recurrence, attempting to illuminate the interaction of gene-environment in HCC. A total of 1233 Chinese Han people were recruited in this study, including 647 healthy controls and 586 HCC cases. Six Tag SNPs (rs10494885, rs2296160, rs3737002, rs3849266, rs669117, rs7525160) of CD35 were selected using HaploView 4.2 program and were genotyped by matrix assisted laser desorption ionization time of flight mass spectrometry method (MALDI-TOF-MS). Overall, mutation genotypes CC/CG of CD35 rs7525160 significantly increased the risk of HCC. Through stratification analysis, CD35 rs7525160 CC/CG genotypes were found to increase HCC risk in younger than 65 years patients, and was closely related to the pathological type of poor prognosis of HCC. Cox proportional hazard ratio model analysis unraveled rs7525160 CC/CG genotype remained a significant independent risk factor for postoperative recurrence of HCC. In conclusion, CD35 rs7525160 polymorphism may contribute to susceptibility and prognosis of HCC in Chinese Han population.

scholarly journals EZ-ALBI Score for Predicting Hepatocellular Carcinoma Prognosis

Liver Cancer ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 734-743
Author(s):  
Kazuya Kariyama ◽  
Kazuhiro Nouso ◽  
Atsushi Hiraoka ◽  
Akiko Wakuta ◽  
Ayano Oonishi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Large Scale ◽  
Regression Coefficient ◽  
Information Criterion ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Highly Correlated ◽  
Survival Risk ◽  
Good Agreement

<b><i>Introduction:</i></b> The ALBI score is acknowledged as the gold standard for the assessment of liver function in patients with hepatocellular carcinoma (HCC). Unlike the Child-Pugh score, the ALBI score uses only objective parameters, albumin (Alb) and total bilirubin (T.Bil), enabling a better evaluation. However, the complex calculation of the ALBI score limits its applicability. Therefore, we developed a simplified ALBI score, based on data from a large-scale HCC database.We used the data of 5,249 naïve HCC cases registered in eight collaborating hospitals. <b><i>Methods:</i></b> We developed a new score, the EZ (Easy)-ALBI score, based on regression coefficients of Alb and T.Bil for survival risk in a multivariate Cox proportional hazard model. We also developed the EZ-ALBI grade and EZ-ALBI-T grade as alternative options for the ALBI grade and ALBI-T grade and evaluated their stratifying ability. <b><i>Results:</i></b> The equation used to calculate the EZ-ALBI score was simple {[T.Bil (mg/dL)] – [9 × Alb (g/dL)]}; this value highly correlated with the ALBI score (correlation coefficient, 0.981; <i>p</i> &#x3c; 0.0001). The correlation was preserved across different Barcelona clinic liver cancer grade scores (regression coefficient, 0.93–0.98) and across different hospitals (regression coefficient, 0.98–0.99), indicating good generalizability. Although a good agreement was observed between ALBI and EZ-ALBI, discrepancies were observed in patients with poor liver function (T.Bil, ≥3 mg/dL; regression coefficient, 0.877). The stratifying ability of EZ-ALBI grade and EZ-ALBI-T grade were good and their Akaike’s information criterion values (35,897 and 34,812, respectively) were comparable with those of ALBI grade and ALBI-T grade (35,914 and 34,816, respectively). <b><i>Conclusions:</i></b> The EZ-ALBI score, EZ-ALBI grade, and EZ-ALBI-T grade are useful, simple scores, which might replace the conventional ALBI score in the future.

Age at onset and outcome in schizophrenia are related to the degree of familial loading

1998 ◽  
Vol 173 (6) ◽  
pp. 494-500 ◽  
Author(s):  
Jaana M. Suvisaari ◽  
Jari Haukka ◽  
Antti Tanskanen ◽  
Jouko K. Lönnqvist
Keyword(s):  
Mixed Models ◽  
Early Onset ◽  
Disability Pension ◽  
Psychotic Disorders ◽  
Age At Onset ◽  
Cox Proportional Hazard Model ◽  
Proportional Hazard ◽  
Proportional Hazard Model ◽  
Cox Proportional Hazard ◽  
The Relationship

BackgroundRecent research suggests that high familial loading is associated with early onset of schizophrenia. Results concerning outcome have been controversial.MethodWe assessed the relationship between familial loading, age at onset and outcome in all Finnish patients with schizophrenia born between 1950 and 1969. Patients and their first-degree relatives were identified using nationwide registers. Familial loading scores were calculated for schizophrenia and for combined psychotic disorders, and patients were accordingly classified into three groups: high (n = 761), intermediate (n = 14 247), and low familial loading (n = 725). Linear mixed models and the Cox proportional hazard model were used in the analyses.ResultsOnset was earliest, hospitalisation longest and risk of retirement in receipt of a disability pension highest in the group with high familial loading, with opposite extremes found in the group with low familial loading.ConclusionsHigh familial loading for schizophrenia is associated with early onset and poor outcome of schizophrenia.

scholarly journals Characteristics and prognosis of hepatocellular carcinoma in multi-transfused patients with thalassemia major. Experience of a single tertiary center.

2020 ◽  
Vol 12 (1) ◽  
pp. e2020013
Author(s):  
Nikolaos Papadopoulos ◽  
Dimitrios Kountouras ◽  
Katerina Malagari ◽  
Maria Tampaki ◽  
Maria Theochari ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Proportional Hazard ◽  
Liver Iron ◽  
Cox Proportional Hazard ◽  
Tertiary Center

Background: In this retrospective study, records of patients with thalassemia major (TM) diagnosed with hepatocellular carcinoma (HCC) from 2008‐2018 were reviewed in order to determine the survival rate and evaluate possible etiological factors associated with survival. Methods: Forty-two TM patients who were diagnosed with HCC have been included in the study. Most of our patients (78.5%) were anti-HCV positive, while 16.5% had evidence of resolved HBV infection. At the time of HCC diagnosis, 78.5% of our patients were diagnosed with cirrhosis, while the vast majority (98%) had normal or mild elevated liver iron concentration (LIC) values. According to Barcelona Clinic Liver Cancer (BCLC) grading system patients were classified as 0-A: 28.5%, B: 57% and as C-D: 14.5%.  HCC has been treated with loco-regional treatment in 78.5% of our patients, while the rest have been treated with sorafenib. Results: Twenty-eight patients (66.5%) have eventually died with a median survival time of 6 months (range: 2-60). Using the Cox proportional hazard model, the only factors who have been associated with poor survival were BCLC stages C and D. Conclusions: In conclusion, BCLC staging is the main prognostic factor of survival in patients with TM who develop HCC, with a median survival time of six months.

scholarly journals Human epididymis protein 4 is a new biomarker to predict the prognosis of progressive fibrosing interstitial lung disease

2020 ◽  
Author(s):  
Naoki Nishiyama ◽  
Masahiro Masuo ◽  
Yoshihisa Nukui ◽  
Tomoya Tateishi ◽  
Mitsuhiro Kishino ◽  
...  
Keyword(s):  
Prospective Observational Study ◽  
Interstitial Lung Diseases ◽  
Proportional Hazard ◽  
Proportional Hazard Model ◽  
High Resolution Computed Tomography ◽  
Human Epididymis Protein 4 ◽  
Derivation Cohort ◽  
Human Epididymis ◽  
Cox Proportional Hazard ◽  
The Relationship

Abstract BACKGROUND The clinical course and prognosis of progressive fibrosing interstitial lung diseases ( PF-ILDs) vary from individual to individual. Predictive serum biomarkers for the management of the disease are needed. Serum human epididymis protein 4 (HE4) has been reported to be elevated in patients with IPF, yet its clinical utility has not been elucidated. We evaluated whether serum HE4 could be a biomarker for patients with PF-ILD. METHODS Serum HE4 was measured in a retrospective study that consisted of 34 patients with PF-ILD and 40 healthy volunteers. The relationship between serum HE4 levels and clinical parameters or prognosis was investigated. To validate the significance of the results, a prospective observational study that consisted of 37 patients with PF-ILD and 40 control patients without PF-ILD was performed.RESULTS Serum HE4 was higher in patients with PF-ILD than in health volunteers ( P < 0.01). A correlation of the serum HE4 levels with the extent of honeycombing on chest high-resolution computed tomography was identified (r = 0.41, P = 0.015). In multivariate analysis by the Cox proportional hazard model, higher HE4 levels (> 238 pmol/l) were associated with elevated mortality risk (HR 7.27, 95% CI 1.56-34.0, P = 0.01 in the derivation cohort; HR 44.3, 95% CI 4.19-468, P < 0.01 in validation cohort). CONCLUSIONS Serum HE4 levels may serve as a new diagnostic and prognostic biomarker for patients with PF-ILD.

scholarly journals CMTM6 significantly relates to PD-L1 and predicts the prognosis of gastric cancer patients

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9536
Author(s):  
Xin Li ◽  
Ling Chen ◽  
Chuan Gu ◽  
Qiaoli Sun ◽  
Jia Li
Keyword(s):  
Gastric Cancer ◽  
Prognostic Indicator ◽  
Proportional Hazard ◽  
Regression Analyses ◽  
Multivariate Logistic Regression ◽  
Related Factors ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Cox Proportional Hazard Regression ◽  
The Relationship

Background The CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is a key regulator of the programed death receptor ligand-1 (PD-L1) protein. However, the usefulness of CMTM6 expression as a prognostic indicator and the relationship between CMTM6 and PD-L1 expression in gastric cancer (GC) remains unclear. Objectives We evaluated the expression and prognostic implications of CMTM6 in GC tissue and its relationship with PD-L1 expression. Patients and methods The protein expressions of CMTM6 and PD-L1 were detected in 122 cases of postoperative GC tissue using immunohistochemical (IHC) assays. Kaplan–Meier survival analysis was used to calculate the survival probability and a log-rank test was used to compare the survival curves. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the clinically-related factors associated with survival. Pearson’s correlation was used to determine the correlation analysis and estimate the statistical significance. The univariate and multivariate logistic regression analyses were used to analyze the relationship between clinically-related factors and PD-L1 expression. Results Kaplan–Meier survival analysis showed that patients with high CMTM6 expression had shorter overall survival (OS) than those with low expression (P < 0.001). The expression of CMTM6 was an independent risk factor for prognosis in multivariate Cox proportional hazard regression analyses (HR:2.221, CI% [1.36–3.628], P = 0.001). The OS of patients with positively expressed PD-L1 was significantly shorter than those with negatively expressed PD-L1 (P = 0.003). The expression of CMTM6 was significantly related to the positive expression of PD-L1 in gastric cancer tissues (r = 0.186, P = 0.041). The expression of CMTM6 was the independent risk factor for PD-L1 expression in multivariate logistic regression analysis (OR:2.538, CI% [1.128–5.714], P = 0.024). Conclusion CMTM6 expression is significantly related to PD-L1 and may be a useful prognostic indicator and a specific therapeutic target for cancer immunotherapy for GC patients.

scholarly journals Human epididymis protein 4 is a new biomarker to predict the prognosis of progressive fibrosing interstitial lung disease

2020 ◽  
Author(s):  
Naoki Nishiyama ◽  
Masahiro Masuo ◽  
Yoshihisa Nukui ◽  
Tomoya Tateishi ◽  
Mitsuhiro Kishino ◽  
...  
Keyword(s):  
Prospective Observational Study ◽  
Interstitial Lung Diseases ◽  
Proportional Hazard ◽  
Proportional Hazard Model ◽  
High Resolution Computed Tomography ◽  
Human Epididymis Protein 4 ◽  
Derivation Cohort ◽  
Human Epididymis ◽  
Cox Proportional Hazard ◽  
The Relationship

Abstract BACKGROUND The clinical course and prognosis of progressive fibrosing interstitial lung diseases ( PF-ILDs) vary from individual to individual. Predictive serum biomarkers for the management of the disease are needed. Serum human epididymis protein 4 (HE4) has been reported to be elevated in patients with IPF, yet its clinical utility has not been elucidated. We evaluated whether serum HE4 could be a biomarker for patients with PF-ILD.METHODS Serum HE4 was measured in a retrospective study that consisted of 34 patients with PF-ILD and 40 healthy volunteers. The relationship between serum HE4 levels and clinical parameters or prognosis was investigated. To validate the significance of the results, a prospective observational study that consisted of 37 patients with PF-ILD and 40 control patients without PF-ILD was performed.RESULTS Serum HE4 was higher in patients with PF-ILD than in health volunteers ( P < 0.01). A correlation of the serum HE4 levels with the extent of honeycombing on chest high-resolution computed tomography was identified (r = 0.41, P = 0.015). In multivariate analysis by the Cox proportional hazard model, higher HE4 levels (> 238 pmol/l) were associated with elevated mortality risk (HR 7.27, 95% CI 1.56-34.0, P = 0.01 in the derivation cohort; HR 44.3, 95% CI 4.19-468, P < 0.01 in validation cohort).CONCLUSIONS Serum HE4 levels may serve as a new diagnostic and prognostic biomarker for patients with PF-ILD.

Incorporating molecular markers in standard prognostic models for DLBCL patients using real-world data.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19251-e19251
Author(s):  
Shivam Mathura ◽  
Vicki Kay Fung ◽  
Keshava Dilwali ◽  
Ashwin Subramanian Lakshmanan
Keyword(s):  
Monoclonal Antibody ◽  
Molecular Markers ◽  
Risk Group ◽  
Risk Groups ◽  
Cox Proportional Hazard Model ◽  
Proportional Hazard ◽  
Proportional Hazard Model ◽  
Real World Data ◽  
Cox Proportional Hazard ◽  
The Relationship

e19251 Background: NCCN-IPI is a prognostic scoring system that outperforms other risk classification mechanisms in diffuse large B-cell lymphoma (DLBCL) but does not consider the molecular profile of patients. We evaluated the predictive value of NCCN-IPI and clinically relevant molecular markers on the overall survival (OS) of patients with diagnosed DLBCL in real-world data (RWD). Methods: Patients diagnosed with DLBCL were identified in the COTA RWD population, and then subset to those with sufficient attributes to calculate NCCN-IPI at diagnosis (age, stage, LDH ratio, performance status, extranodal disease) and those who received a monoclonal antibody targeting CD20 (n = 383). This population was further filtered to patients tested for BCL-2, BCL-6, and C-MYC (n = 176). Disease characteristics were summarized using descriptive statistics and chi-square tests of independence were performed to assess the relationship between NCCN-IPI Risk-Group and molecular marker results. A Cox proportional hazard model was used to identify prognostic features of OS. Results: There were statistically significant relationships between NCCN-IPI Risk-Group and both BCL-2 (p = 0.007) and C-MYC (p < 0.001) after Bonferroni correction for the number of molecular markers tested. A Cox proportional hazard model with the three molecular markers as covariates revealed a statistically significant correlation between the presence of C-MYC alteration and decreased OS (HR = 2.02, CI: 1.24-3.32, p = 0.005). However, when NCCN-IPI Risk-Group was added as a covariate, the relationship between C-MYC and OS was no longer significant. The hazard ratios associated with high-intermediate and high risk groups were larger than that of the low-intermediate group. All three of these risk groups were statistically significant in the model (p < 0.038). Conclusions: The inclusion of molecular markers to the NCCN-IPI prognostic model did not increase predictive power in this RWD cohort. We validated the NCCN-IPI model and found it to be a robust tool for classifying risk and estimating OS in patients who have received a CD20 monoclonal antibody. A larger sample size would increase power to further explore the impact of molecular markers on overall survival. [Table: see text]

Abstract 15567: Increased Visceral Fat Volume is Associated With Aortic Inflammation and Cardiovascular Events

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Richard A Takx ◽  
Amparo L Figueroa ◽  
Megan H MacNabb ◽  
Amr Abdelbaky ◽  
Zachary R Lavender ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cardiovascular Events ◽  
Hazard Models ◽  
Proportional Hazard ◽  
Proportional Hazard Models ◽  
Cox Proportional Hazard ◽  
Cox Proportional Hazard Models ◽  
Arterial Inflammation ◽  
Visceral Adipose ◽  
The Relationship

Introduction: While the relationship between obesity and cardiovascular disease (CVD) is well-established, mechanisms underlying this relationship are not well elucidated. Hypothesis: Our hypothesis is that visceral adipose tissue (VAT) volume, aortic inflammation and the risk of subsequent cardiovascular events are linked together. Methods: Individuals who underwent 18F-FDG PET/CT imaging were included. VAT volume, subcutaneous adipose tissue (SAT) volume and aortic FDG uptake were measured while blinded to clinical data. Cardiovascular events were adjudicated by independent cardiologists. Thereafter, the relationship between VAT volume and aortic FDG activity and cardiovascular events was evaluated using Cox proportional hazard models. Results: The final analysis included 415 patients with a median age of 55 (P25-P75: 45-65) years and a median BMI of 26.4 (P25- P75: 23.4-30.9) kg/m2. VAT and SAT volume were significantly higher in obese individuals. 32 subjects experienced cardiovascular event during a median follow-up of 4 years. Cox proportional hazard models showed that VAT volume was a associated with cardiovascular events (hazard ratio, HR (95% CI): 1.15 (1.06-1.25, p<0.001). This remained significant after correcting for age, BMI and aortic TBR (p<0.05). SAT was not predictive of cardiovascular events. VAT volume was associated with arterial inflammation (r=0.29, p<0.001, Figure 1). The combination of high aortic inflammation and high VAT volume was associated with significant worse survival (p<0.05). Conclusions: We observed that VAT volume is a predictor of subsequent cardiovascular events. Moreover, our results indicate a link between visceral adipose tissue volume and arterial inflammation, which may explain some of VAT's association with cardiovascular events.

BP in Young Adults with CKD and Associations with Cardiovascular Events and Decline in Kidney Function

2021 ◽  
pp. ASN.2020081156
Author(s):  
Alexander J. Kula ◽  
David K. Prince ◽  
Joseph T. Flynn ◽  
Nisha Bansal
Keyword(s):  
Heart Failure ◽  
Young Adults ◽  
Cardiovascular Events ◽  
Treatment Strategies ◽  
Proportional Hazard ◽  
Ckd Progression ◽  
Cox Proportional Hazard ◽  
Cox Proportional Hazard Models ◽  
The Relationship

BackgroundBP is an important modifiable risk factor for cardiovascular events and CKD progression in middle-aged or older adults with CKD. However, studies describing the relationship between BP with outcomes in young adults with CKD are limited.MethodsIn an observational study, we focused on 317 young adults (aged 21–40 years) with mild to moderate CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Exposures included baseline systolic BP evaluated continuously (per 10 mm Hg increase) and in categories (<120, 120–129, and ≥130 mm Hg). Primary outcomes included cardiovascular events (heart failure, myocardial infarction, stroke, or all-cause death) and CKD progression (50% decline of eGFR or ESKD). We used Cox proportional hazard models to test associations between baseline systolic BP with cardiovascular events and CKD progression.ResultsCardiovascular events occurred in 52 participants and 161 had CKD progression during median follow-up times of 11.3 years and 4.1 years, respectively. Among those with baseline systolic BP ≥130 mm Hg, 3%/yr developed heart failure, 20%/yr had CKD progression, and 2%/yr died. In fully adjusted models, baseline systolic BP ≥130 mm Hg (versus systolic BP<120 mm Hg) was significantly associated with cardiovascular events or death (hazard ratio [HR], 2.13; 95% confidence interval [95% CI], 1.05 to 4.32) and CKD progression (HR, 1.68; 95% CI, 1.10 to 2.58).ConclusionsAmong young adults with CKD, higher systolic BP is significantly associated with a greater risk of cardiovascular events and CKD progression. Trials of BP management are needed to test targets and treatment strategies specifically in young adults with CKD.

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