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Hyuk Lee

Publications and source records attributed to Hyuk Lee.

2 recordsLinked to original sources

C-Reactive Protein-Based Composite Indices for Predicting Tumor Overgrowth Restenosis After Partially Covered Duodenal Stenting in Gastric Cancer: A Cohort Study.

BACKGROUND/OBJECTIVES: Partially covered duodenal stents rapidly relieve malignant gastric outlet obstruction, but tumor overgrowth restenosis limits durability. We compared six preprocedural inflammatory, nutritional, and immune indices for predicting this outcome in patients with gastric cancer. METHODS: We retrospectively analyzed 68 consecutive patients from a prospectively maintained cohort. The primary endpoint was endoscopically or radiologically confirmed tumor overgrowth restenosis. Discrimination was assessed using receiver operating characteristic curves (pairwise DeLong tests with Bonferroni correction) and time-dependent areas under the curve (AUCs) accounting for death as a competing risk. Multivariable cause-specific Cox models were restricted to preprocedural covariates; post-stenting chemotherapy or radiotherapy was examined in time-dependent sensitivity analyses. RESULTS: Technical and clinical success rates were 100% and 94.1%. Seventeen patients (25.0%) developed restenosis at a median of 66 days. The C-reactive protein-albumin-lymphocyte (CALLY) index showed the highest AUC (0.859), followed by the C-reactive protein-to-albumin ratio (CAR; 0.822) and neutrophil-to-lymphocyte ratio (0.774); these three indices did not differ significantly. At an exploratory, internally derived cutoff of ≤0.110, CALLY had 76.5% sensitivity and 84.3% specificity and remained associated with restenosis after adjustment for stenosis site and stent length (adjusted hazard ratio, 12.30; 95% confidence interval, 3.89-38.83; C-index, 0.836), with consistent results in continuous, time-dependent, and tumor-covariate-adjusted analyses. The 180-day cumulative incidence was 52.4% with low CALLY versus 4.3% with high CALLY. CONCLUSIONS: C-reactive protein-based indices showed the highest numerical discrimination, although pairwise differences among CALLY, CAR, and NLR were not statistically significant. CALLY is a promising exploratory biomarker for restenosis risk stratification, but its cutoff should not guide clinical decisions until externally validated.

C-reactive protein

Stool Protein Mass Spectrometry Identifies Biomarkers for Early Detection of Diffuse-type Gastric Cancer.

There is a high unmet need for early detection approaches for diffuse gastric cancer (DGC). We examined whether the stool proteome of mouse models of gastric cancer (GC) and individuals with hereditary diffuse gastric cancer (HDGC) have utility as biomarkers for early detection. Proteomic mass spectrometry of the stool of a genetically engineered mouse model driven by oncogenic KrasG12D and loss of p53 and Cdh1 in gastric parietal cells [known as Triple Conditional (TCON) mice] identified differentially abundant proteins compared with littermate controls. Immunoblot assays validated a panel of proteins, including actinin alpha 4 (ACTN4), N-acylsphingosine amidohydrolase 2 (ASAH2), dipeptidyl peptidase 4 (DPP4), and valosin-containing protein (VCP), as enriched in TCON stool compared with littermate control stool. Immunofluorescence analysis of these proteins in TCON stomach sections revealed increased protein expression compared with littermate controls. Proteomic mass spectrometry of stool obtained from patients with HDGC with CDH1 mutations identified increased expression of ASAH2, DPP4, VCP, lactotransferrin (LTF), and tropomyosin-2 relative to stool from healthy sex- and age-matched donors. Chemical inhibition of ASAH2 using C6 urea ceramide was toxic to GC cell lines and GC patient-derived organoids. This toxicity was reversed by adding downstream products of the S1P synthesis pathway, which suggested a dependency on ASAH2 activity in GC. An exploratory analysis of the HDGC stool microbiome identified features that correlated with patient tumors. Herein, we provide evidence supporting the potential of analyzing stool biomarkers for the early detection of DGC. Prevention Relevance: This study highlights a novel panel of stool protein biomarkers that correlate with the presence of DGC and has potential use as early detection to improve clinical outcomes.

Feces