ABSTRACT
BACKGROUND: liver cancer is a malignant tumor with a high morbidity and mortality that endangers human health. High mobility group A2 (HMGA2) is a chromosome associated protein that participates in embryogenesis, tissue development, tumorigenesis and development. OBJECTIVE: to explore the relationship between HMGA2 expression and the clinicopathological parameters and survival of liver cancer patients using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (HCC) data. METHODS: RNA-sequencing data and the corresponding clinical characteristics of the patients were downloaded from the Atlas database. The Chi-squared test was used to assess the relationship between HMGA2 expression and clinical variables. Cox regression analysis was used to compare survival rates between the high- and low-expressing groups; the p-values and Kaplan-Meier survival curves were compared using the log-rank test. RESULTS: RNA-seq data from 373 cases of liver cancer cases were analyzed. HMGA2 was overexpressed in liver cancer and significantly associated with gender (p = 0.0357), T classification (p = 0.0063), clinical classification (p = 0.0026) and overall survival (p = 0.0386). According to the multivariate analysis, HMGA2 could independently predict overall survival in liver cancer. CONCLUSIONS: HMGA2 independently predicts poor prognosis in liver cancer and serves as a molecular marker to determine disease prognosis
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Subject(s)
Humans , Liver Neoplasms/blood , Liver Neoplasms/mortality , HMGB2 Protein/blood , Biomarkers, Tumor/blood , Gene Expression Regulation, Neoplastic , Case-Control Studies , Survival Analysis , PrognosisABSTRACT
High-mobility group box (HMGB) family is related to inflammatory diseases. We investigated whether serum HMGB2 levels are related to myocardial infarction (MI) severity and major adverse cardiac events (MACE) during MI. We included 432 consecutive patients with ST-segment elevation myocardial infarction and 312 controls. Serum HMGB2 levels were significantly higher in MI patients than in controls. Increased HMGB2 levels were associated with MACE and negatively with ejection fraction in MI patients. HMGB2 was an independent determinant of MACE in logistic regression analysis. HMGB2 protein (10 µg) or saline was injected intramyocardially in MI rats, with or without coadministration of the NADPH oxidase inhibitor apocynin. After 72 h, pathological, echocardiographic, and hemodynamic examinations showed that HMGB2 increased infarct size and worsened cardiac function in MI rats. Moreover, HMGB2 administration enhanced reactive oxygen species (ROS) production, cell apoptosis, inflammation, and autophagosome clearance impairment, which were attenuated by coadministration of apocynin or knock down of receptor for advanced glycation end products (RAGE). In conclusion, increased serum HMGB2 levels are associated with MI severity and MACE at 1 mo. HMGB2 promotes myocardial ischemic injury in rats and hypoxic H9C2 cell damage via ROS provoked by RAGE.NEW & NOTEWORTHY We demonstrate that serum high-mobility group box 2 is associated with major adverse cardiac events at 1 mo in myocardial infarction patients. Mechanistically, high-mobility group box 2 promotes reactive oxygen species production via receptor for advanced glycation end products signaling in ischemic myocardium, thereby aggravating cell apoptosis, inflammation, and autophagosome clearance impairment. This study reveals that high-mobility group box 2 is a novel factor enhancing ischemic injury in myocardial infarction.
