Background High mobility group protein B2 (HMGB2) is a multifunctional protein that plays various roles in different cellular compartments. Moreover, HMGB2 serves as a potential prognostic biomarker and therapeutic target for lung adenocarcinoma (LUAD). Methods In this study, the expression pattern, prognostic implication, and potential role of HMGB2 in LUAD were evaluated using the integrated bioinformatics analyses based on public available mRNA expression profiles from The Cancer Genome Atlas and Gene Expression Omnibus databases, both at the single-cell level and the tissue level. Further study in the patient-derived samples was conducted to explore the correlation between HMGB2 protein expression levels with tissue specificity, (tumor size-lymph node-metastasis) TNM stage, pathological grade, Ki-67 status, and overall survival. In vitro experiments, such as CCK-8, colony-formation and Transwell assay, were performed with human LUAD cell line A549 to investigate the role of HMGB2 in LUAD progression. Furthermore, xenograft tumor model was generated with A549 in nude mice. Results The results showed that the HMGB2 expression was higher in the LUAD samples than in the adjacent normal tissues and was correlated with high degree of malignancy in different public data in this study. Besides, over-expression of HMGB2 promoted A549 cells proliferation and migration while knocking down of HMGB2 suppressed the tumor promoting effect. Conclusions Our study indicated that HMGB2 was remarkably highly expressed in LUAD tissues, suggesting that it is a promising diagnostic and therapeutic marker for LUAD in the future.
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This work was aimed at analyzing the correlation between the methylation level of the M6A gene in esophageal cancer (EC) and the prognosis of patients based on bioinformatics technology and evaluating the prognostic predictive values of different data mining models. 80 EC patients and 80 healthy people were selected, and the serum of the patients was collected to detect the level of DNA methyltransferase. During the radical resection of EC, tumor tissues and adjacent normal tissues were collected from patients to detect the methylation level of the M6A gene. COX regression analysis was employed to analyze the independent risk factors (IRFs) of M6A gene methylation and other treatments affecting the prognosis of EC patients. The particle swarm optimization (PSO) algorithm was introduced to improve the fuzzy C -means clustering (FCM) algorithm. The differences in the prognostic prediction efficiency of logistic regression analysis (LRA), decision tree (DT) C5.0, artificial neural network (ANN), support vector machine (SVM), and improved FCM (IFCM) models were compared. The levels of DNA methyltransferase and human histone deacetylase 1 (HSD-1) in EC patients were increased greatly ( P < 0.05 ). The methylation rates and methylation levels of M6A methylation regulators (ALKBH5, HNRNPC, METTL3, WTAP, RBM15, YTHDC1, YTHDF1, and FTO) in EC tissues were obviously higher ( P < 0.05 ). The survival time of high-risk EC patients was much shorter than that of low-risk patients ( P < 0.05 ). Univariate and multivariate COX regression analysis showed that gender, tumor grade, TNM grade, degree of infiltration, and methylation of ALKBH5, HNRNPC, and METTL3 genes were IRFs for the prognosis of EC patients ( P < 0.05 ). The areas under the ROC curve (AUCs) of LRA, DT C5.0, ANN, SVM, and IFCM algorithms for predicting the prognosis of patients were 0.813, 0.857, 0.895, 0.926, and 0.958, respectively, and the IFCM model had the best diagnostic effect. In conclusion, the detection of bioinformatics technology showed no obvious DNA methylation in EC patients, and the elevated levels of M6A methylation regulators in patients were an IRF affecting the prognosis of patients. In addition, the fuzzy data mining model can be undertaken as the preferred method for prognosis prediction of EC patients.
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