Dataset Information

Child-Pugh Score and ABCG2-rs2231142 Genotype Independently Predict Survival in Advanced Hepatoma Patients Treated with Sorafenib.

ABSTRACT: Patients with advanced hepatocellular carcinoma (HCC) are treated by immunotherapy and/or targeted agents, such as sorafenib. Several single nucleotide polymorphisms (SNPs) and clinical scores have been proposed as prognostic markers in HCC patients treated with sorafenib. This study aimed to validate the prognostic values of these markers in a tertiary referral medical center. Two independent cohorts (cohort-1 [n = 97] and cohort-2 [n = 60]) of advanced HCC patients treated with sorafenib monotherapy were enrolled. Univariate followed by multivariate Cox proportional hazard analysis identified Child-Pugh (CP) score (p < 0.001) and renal insufficiency during treatment (p < 0.001) as independent predictors in cohort-1 patients. The same analytic method revealed ascites (p = 0.000), CP score (p = 0.001), infection during treatment (p < 0.001), and ATP-binding cassette subfamily G member 2 (ABCG2)-rs2231142 genotype (p = 0.003) as independent predictors in cohort-2 patients. ABCG2-rs2231142 genotype "CC" was associated with unfavorable overall survival in sorafenib-treated HCC patients. In conclusion, the CP score and ABCG2-rs2231142 genotype served as independent survival predictors for advanced HCC patients receiving sorafenib treatment.

SUBMITTER: Huang PH

PROVIDER: S-EPMC9105641 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Child-Pugh Score and <i>ABCG2</i>-rs2231142 Genotype Independently Predict Survival in Advanced Hepatoma Patients Treated with Sorafenib.

Huang Po-Han PH Yu Jen J Chu Yin-Yi YY Lin Yang-Hsiang YH Yeh Chau-Ting CT

Journal of clinical medicine 20220502 9

Patients with advanced hepatocellular carcinoma (HCC) are treated by immunotherapy and/or targeted agents, such as sorafenib. Several single nucleotide polymorphisms (SNPs) and clinical scores have been proposed as prognostic markers in HCC patients treated with sorafenib. This study aimed to validate the prognostic values of these markers in a tertiary referral medical center. Two independent cohorts (cohort-1 [n = 97] and cohort-2 [n = 60]) of advanced HCC patients treated with sorafenib monot ...[more]

PMID: 35566676

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Project description:BackgroundWhat combination of risk factors for Alzheimer's disease (AD) are most predictive of cognitive decline in cognitively unimpaired individuals remains largely unclear. We studied associations between APOE genotype, AD-Polygenic Risk Scores (AD-PRS), amyloid-β pathology and decline in cognitive functioning over time in a large sample of cognitively unimpaired older individuals.MethodsWe included 276 cognitively unimpaired older individuals (75 ± 10 years, 63% female) from the EMIF-AD PreclinAD cohort. An AD-PRS was calculated including 83 genome-wide significant variants. The APOE gene was not included in the PRS and was analyzed separately. Baseline amyloid-β status was assessed by visual read of [18F]flutemetamol-PET standardized uptake value images. At baseline and follow-up (2.0 ± 0.4 years), the cognitive domains of memory, attention, executive function, and language were measured. We used generalized estimating equations corrected for age, sex and center to examine associations between APOE genotype and AD-PRS with amyloid-β status. Linear mixed models corrected for age, sex, center and education were used to examine associations between APOE genotype, AD-PRS and amyloid-β status, and their interaction on changes in cognitive functioning over time.ResultsFifty-two participants (19%) had abnormal amyloid-β, and 84 participants (31%) carried at least one APOE ε4 allele. APOE genotype and AD-PRS were both associated with abnormal amyloid-β status. Increasingly more risk-full APOE genotype, a high AD-PRS and an abnormal amyloid-β status were associated with steeper decline in memory functioning in separate models (all p ≤ 0.02). A model including 4-way interaction term (APOE×AD-PRS×amyloid-β×time) was not significant. When modelled together, both APOE genotype and AD-PRS predicted steeper decline in memory functioning (APOE β(SE)=-0.05(0.02); AD-PRS β(SE)=-0.04(0.01)). Additionally, when modelled together, both amyloid-β status and AD-PRS predicted a steeper decline in memory functioning (amyloid-β β(SE)=-0.07(0.04); AD-PRS β(SE)=-0.04(0.01)). Modelling both APOE genotype and amyloid-β status, we observed an interaction, in which APOE genotype was related to steeper decline in memory and language functioning in amyloid-β abnormal individuals only (β(SE)=-0.13(0.06); β(SE)=-0.22(0.07), respectively).ConclusionOur results suggest that APOE genotype is related to steeper decline in memory and language functioning in individuals with abnormal amyloid-β only. Furthermore, independent of amyloid-β status other genetic risk variants contribute to memory decline in initially cognitively unimpaired older individuals.

Dataset Information

Child-Pugh Score and ABCG2-rs2231142 Genotype Independently Predict Survival in Advanced Hepatoma Patients Treated with Sorafenib.

Publications

Child-Pugh Score and <i>ABCG2</i>-rs2231142 Genotype Independently Predict Survival in Advanced Hepatoma Patients Treated with Sorafenib.

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