(1) Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Although various serum enzymes have been utilized for the diagnosis and prognosis of HCC, the currently available biomarkers lack the sensitivity needed to detect HCC at early stages and accurately predict treatment responses. (2) Methods: We utilized our highly sensitive cell-free DNA (cfDNA) detection system, in combination with a machine learning algorithm, to provide a platform for improved diagnosis and prognosis of HCC. (3) Results: cfDNA, specifically alpha-fetoprotein (AFP) expression in captured cfDNA, demonstrated the highest accuracy for diagnosing malignancies among the serum/plasma biomarkers used in this study, including AFP, aspartate aminotransferase, alanine aminotransferase, albumin, alkaline phosphatase, and bilirubin. The diagnostic/prognostic capability of cfDNA was further improved by establishing a cfDNA score (cfD_HCC), which integrated the total plasma cfDNA levels and cfAFP-DNA expression into a single score using machine learning algorithms. (4) Conclusion: The cfD_HCC score demonstrated significantly improved accuracy in determining the pathological features of HCC and predicting patients’ survival outcomes compared to the other biomarkers. The results presented herein reveal that our cfDNA capture/analysis platform is a promising approach to effectively utilize cfDNA as a biomarker for the diagnosis and prognosis of HCC.

OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease. Evidence indicates a relationship between sugar-sweetened beverage (SSB) consumption and MASLD development; however, the effects of specific SSB types on MASLD remain underexplored. This study investigated the association between consumption of 3 distinct types of SSBs and MASLD in Korean adults.METHODS: We analyzed data from the Korea National Health and Nutrition Examination Survey 2012-2016, including 8,310 participants aged 40-64 years. SSB consumption (soft drinks, fruit drinks, and Korean traditional drinks) was assessed using a food frequency questionnaire. MASLD was defined as a hepatic steatosis index ≥36 in the presence of any cardiometabolic risk factor. Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for relevant covariates.RESULTS: Compared to non-drinkers, consumption of soft drinks (≥3 serving/wk) was associated with higher odds of MASLD (OR, 1.36; 95% CI, 1.02 to 1.81; p for trend=0.03), while consumption of Korean traditional drinks (≥3 serving/wk) was associated with lower odds of MASLD (OR, 0.63; 95% CI, 0.45 to 0.89; p for trend=0.01). No association was found between fruit drink consumption and MASLD. In sex-stratified analysis (p-interaction=0.38), an inverse association between Korean traditional drinks and MASLD was observed in male (OR, 0.57; 95% CI, 0.34 to 0.95; p for trend=0.03), but not in female (OR, 0.72; 95% CI, 0.45 to 1.14; p for trend=0.17).CONCLUSIONS: Consuming soft drinks at least 3 times per week was positively associated with MASLD, whereas an equivalent intake of Korean traditional drinks was inversely associated with MASLD.

During microbial infection, bystander CD8+ T cells that are not specific to infecting pathogens can be activated by cytokines, such as IL-15. However, the tissue-homing properties of bystander-activated CD8+ T cells have not been elucidated. Here, we examined the effects of IL-15 on the expression of chemokine receptors on CD8+ T cells and their migration. We found that IL-15 up-regulates CCR5 in memory CD8+ T cells in the absence of TCR stimulation and enhances CCR5-dependent migration in vitro and in vivo. IL-15-induced CCR5 up-regulation was abrogated by concurrent TCR stimulation, indicating that CCR5 is up-regulated in bystander-activated CD8+ T cells. Moreover, CCR5 signals increased proliferation and cytotoxic protein expression in IL-15-treated memory CD8+ T cells. CCR5 up-regulation in bystander-activated CD8+ T cells was associated with severe liver injury in patients with acute hepatitis A. Taken together, the results indicate that CCR5 up-regulation by IL-15 mediates the migration of bystander-activated CD8+ T cells.

Although the roles of erythroblastic leukemia viral oncogene homolog 2 (ERBB2), neuregulin 4 (NRG4), and mitogen-inducible gene 6 (MIG6) in epidermal growth factor receptor signaling in hepatocellular carcinoma (HCC) and other malignancies have been previously investigated, the prognostic value of their serum levels in HCC remains undetermined. In the present study, correlations between serum levels and tumor characteristics, overall survival, and tumor recurrence were analyzed. Furthermore, the prognostic potential of the serum levels of these biomarkers was evaluated relative to that of alpha-fetoprotein. Both ERBB2 and NRG4 correlated with the Barcelona Clinic Liver Cancer stage, ERBB2 correlated with the tumor-maximal diameter, and NRG4 correlated with a tumor number. Cox proportional hazards regression analysis revealed that ERBB2 (hazard ratio [HR], 2.719; p = 0.007) was an independent prognostic factor for overall survival. Furthermore, ERBB2 (HR, 2.338; p = 0.002) and NRG4 (HR, 431.763; p = 0.001) were independent prognostic factors for tumor recurrence. The products of ERBB2 and NRG4 had a better area under the curve than alpha-fetoprotein for predicting 6-month, 1-year, 3-year, and 5-year mortality. Therefore, these factors could be used to evaluate prognosis and monitor treatment response in patients with HCC.

Background: Circulating tumor DNA (ctDNA) and exosome have been widely researched in the field of medical technology and diagnosis platforms. The purpose of our study was to improve the capturing properties of ctDNA and exosome, which involved combining two beads using approaches that may provide a new method for cancer diagnoses. Methods: We present a dual isolation system including a polydopamine (PDA)–silica-coated alginate bead for circulating tumor DNA (ctDNA) capture and an anti-CD63 immobilized bead for exosome capture. We examined the ctDNA mutation in pre-operative plasma samples obtained from 91 colorectal cancer (CRC) patients using a droplet digital PCR (ddPCR). Results: The area under the curve (AUROC) of ctKRAS G12D mutation in the buffy coat was 0.718 (95% CI: 0.598−0.838; p = 0.001). Patients with CRC that had unmethylation of MLH1 and MSH2 showed significantly higher buffy coat ctKRAS G12D mutations, ascites ctKRAS G12D mutations, miR-31-5, and mixed scores than the patients with a methylation of MLH1 and MSH2. Conclusion: Our proposed alginate bead using the specific gravity-free method suggests that the screening of mutated ctKRAS DNA and miR-31-5 by liquid biopsy aids in identifying the patients, predicting a primary tumor, and monitoring in the early detection of a tumor.