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1.
J Cell Mol Med ; 28(8): e18264, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38526027

RESUMO

Acute myocardial infarction (AMI) increasingly precipitates severe heart failure, with diagnoses now extending to progressively younger demographics. The focus of this study was to pinpoint critical genes linked to both AMI and anoikis, thereby unveiling potential novel biomarkers for AMI detection and intervention. Differential analysis was performed to identify significant differences in expression, and gene functionality was explored. Weighted gene coexpression network analysis (WGCNA) was used to construct gene coexpression networks. Immunoinfiltration analysis quantified immune cell abundance. Protein-protein interaction (PPI) analysis identified the proteins that interact with theanoikis. MCODE identified key functional modules. Drug enrichment analysis identified relevant compounds explored in the DsigDB. Through WGCNA, 13 key genes associated with anoikis and differentially expressed genes were identified. GO and KEGG pathway enrichment revealed the regulation of apoptotic signalling pathways and negative regulation of anoikis. PPI network analysis was also conducted, and 10 hub genes, such as IL1B, ZAP70, LCK, FASLG, CD4, LRP1, CDH2, MERTK, APOE and VTN were identified. IL1B were correlated with macrophages, mast cells, neutrophils and Tcells in MI, and the most common predicted medications were roxithromycin, NSC267099 and alsterpaullone. This study identified key genes associated with AMI and anoikis, highlighting their role in immune infiltration, diagnosis and medication prediction. These findings provide valuable insights into potential biomarkers and therapeutic targets for AMI.


Assuntos
Anoikis , Infarto do Miocárdio , Humanos , Anoikis/genética , Caderinas , Expressão Gênica , Infarto do Miocárdio/genética , Biomarcadores
2.
Mediators Inflamm ; 2023: 9658912, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37205010

RESUMO

Background: Gefitinib resistance remains a major problem in the treatment of lung cancer. However, the underlying mechanisms involved in gefitinib resistance are largely unclear. Methods: Open-accessed data of lung cancer patients were downloaded from The Cancer Genome Atlas Program and Gene Expression Omnibus databases. CCK8, colony formation, and 5-ethynyl-2'-deoxyuridine assays were utilized to evaluate the cell proliferation ability. Transwell and wound-healing assays were utilized to evaluate the cell invasion and migration ability. Quantitative real-time PCR was utilized to detect the RNA level of specific genes. Results: Here, we obtained the expression profile data of wild and gefitinib-resistant cells. Combined with the data from the TCGA and GDSC databases, we identified six genes, RNF150, FAT3, ANKRD33, AFF3, CDH2, and BEX1, that were involved in gefitinib resistance in both cell and tissue levels. We found that most of these genes were expressed in the fibroblast of the NSCLC microenvironment. Hence, we also comprehensively investigated the role of fibroblast in the NSCLC microenvironment, including its biological effect and cell interaction. Ultimately, CDH2 was selected for further analysis for its prognosis correlation. In vitro experiments presented the cancer-promoting role of CDH2 in NSCLC. Moreover, cell viability detection showed that the inhibition of CDH2 could significantly decrease the IC50 of gefitinib in NSCLC cells. GSEA showed that CDH2 could significantly affect the pathway activity of PI3K/AKT/mTOR signaling. Conclusions: This study is aimed at investigating the underlying mechanism involved in gefitinib resistance to lung cancer. Our research has improved researchers' understanding of gefitinib resistance. Meanwhile, we found that CDH2 could lead to gefitinib resistance through PI3K/AKT/mTOR signaling.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Receptores ErbB/metabolismo , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proliferação de Células/genética , Serina-Treonina Quinases TOR/farmacologia , Linhagem Celular Tumoral , Microambiente Tumoral , Proteínas de Membrana
4.
Front Oncol ; 12: 1068198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568178

RESUMO

Background: Prediction of prognosis for patients with esophageal cancer(EC) is beneficial for their postoperative clinical decision-making. This study's goal was to create a dependable machine learning (ML) model for predicting the prognosis of patients with EC after surgery. Methods: The files of patients with esophageal squamous cell carcinoma (ESCC) of the thoracic segment from China who received radical surgery for EC were analyzed. The data were separated into training and test sets, and prognostic risk variables were identified in the training set using univariate and multifactor COX regression. Based on the screened features, training and validation of five ML models were carried out through nested cross-validation (nCV). The performance of each model was evaluated using Area under the curve (AUC), accuracy(ACC), and F1-Score, and the optimum model was chosen as the final model for risk stratification and survival analysis in order to build a valid model for predicting the prognosis of patients with EC after surgery. Results: This study enrolled 810 patients with thoracic ESCC. 6 variables were ultimately included for modeling. Five ML models were trained and validated. The XGBoost model was selected as the optimum for final modeling. The XGBoost model was trained, optimized, and tested (AUC = 0.855; 95% CI, 0.808-0.902). Patients were separated into three risk groups. Statistically significant differences (p < 0.001) were found among all three groups for both the training and test sets. Conclusions: A ML model that was highly practical and reliable for predicting the prognosis of patients with EC after surgery was established, and an application to facilitate clinical utility was developed.

5.
Dis Esophagus ; 35(10)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-35373248

RESUMO

BACKGROUND AND PURPOSE: This meta-analysis assesses the surgical outcomes between robot-assisted minimally-invasive McKeown esophagectomy and conventional one. METHOD: This meta-analysis searched the Web of Science, PUBMED, and EMBASE from the database's inception to January 2022. Altogether, 1073 records were identified in the literature search. Studies that evaluated the outcomes between robot-assisted minimally-invasive McKeown esophagectomy and conventional one among postoperative patients with oesophageal neoplasms were included. The assessed outcomes involved complications and clinical outcomes. In addition, heterogeneity was analyzed, and evidence quality was evaluated. RESULT: Evidence indicated that RAMIE (minimally-invasive esophagectomy assisted with robot) decreased incidences of lung complications and hospital stay as well as increased harvested lymph nodes. CONCLUSIONS: There was currently little evidence from randomized studies depicting that robot surgery manifested a clear overall advantage, but there was growing evidence regarding the clinical benefits of robot-assisted minimally invasive McKeown esophagectomy over conventional one.


Assuntos
Neoplasias Esofágicas , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento
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