ABSTRACT
OBJECTIVE: This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment. METHODS: HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues. RESULTS: ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy. CONCLUSION: This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.
Subject(s)
Alcohol Dehydrogenase , Biomarkers, Tumor , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/genetics , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Liver Neoplasms/mortality , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Prognosis , Alcohol Dehydrogenase/genetics , Alcohol Dehydrogenase/metabolism , Male , Female , Gene Expression Regulation, Neoplastic , Kaplan-Meier EstimateABSTRACT
OBJECTIVE: To develop a qualitative and quantitative determination of multiple components for quality control of Hugu Capsule, a composite prescription in TCM. METHODS: HPLC analysis was performed on a Kromasil C18 column (5.0 microm, 250 mm x 4.6 mm) by gradient elution with methanol-acetonitrile-1% glacial acetic acid as the mobile phase at a flow-rate of 0.8 mL/min,the detection wavelengths were set at 270, 283, 320 and 325 nm at the temperature of 30 degrees C. RESULTS: Five components: chlorogenic acid, tetrahydroxy stilbene glucoside, ferulaic acid, naringin and icariin were simultaneously analyzed in this study. The calibration curves were exhibited linear regressions of at least r > 0.9992. The injection precision,the intra-day precisions and the analysis repeatability were evaluated with the RSD values were all less than 5%. The mean recoveries of the five components were ranged from 97.4% to 99.4%, and RSD values all were less than 1.72%. CONCLUSION: This method is found to be convenient, fast, accurate, and is applicable to analyze the multi-constituents in Hugu Capsule.
Subject(s)
Chlorogenic Acid/analysis , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Flavanones/analysis , Glucosides/analysis , Stilbenes/analysis , Capsules , Coumaric Acids/analysis , Drug Combinations , Drugs, Chinese Herbal/isolation & purification , Flavonoids/analysis , Quality Control , Reproducibility of ResultsABSTRACT
Objective: This study aimed to investigate the role of ficolin-2 (FCN2) in the development and course of hepatocellular carcinoma (HCC) and to contribute to the evolution of innovative HCC therapeutics. Methods: Oncomine, GEPIA (Gene Expression Profiling Interactive Analysis), TISIDB (Tumor Immune System Interactions and Drug Bank database), UALCAN (University of Alabama at Birmingham Cancer data analysis portal), UCSC (University of California, Santa Cruz), R package, the Kaplan-Meier technique, Cox regression analysis, LinkedOmics, Pearson's correlation, and a nomogram were used to investigate the prognostic value of FCN2 in HCC. Co-expressed genes were screened. A protein-protein interaction network was created using the STRING database. Finally, immunohistochemistry was performed to establish the expression of FCN2 in HCC tissues. A pan-cancer study centered on HCC-related molecular analysis was also conducted to look for a link between FCN2 and immune infiltration, immune modulators, and chemokine receptors. Results: In HCC tissues, the expression of FCN2 was observed to be lower than that in normal tissues. This was connected to the HCC marker alpha-fetoprotein, showing that FCN2 is involved in the development and progression of cancer. FCN2 may act through Staphylococcus aureus infection, lectins, and other pathways. Furthermore, at the immune level, the expression of FCN2 in HCC was associated with some immune cell infiltration, immunomodulators, and chemokine receptors. Conclusion: FCN2 may be an immune checkpoint inhibitor for HCC, creating a breakthrough in the treatment of HCC.