Background The dysregulation of RNA methylation has been demonstrated to contribute to tumorigenicity and progression in recent years. However, the alteration of N1-methyladenosine (m1A) methylation and its role in hepatocellular carcinoma (HCC) remain unclear. Methods We systematically investigated the modification patterns of 10 m1A regulators in HCC samples and evaluated the metabolic characteristics of each pattern. A scoring system named the m1Ascore was developed using principal component analysis. The clinical value of the m1Ascore in risk stratification and drug screening was further explored. Results Three m1A modification patterns with distinct metabolic characteristics were identified, corresponding to the metabolism-high, metabolism-intermediate and metabolism-excluded phenotypes. Patients were divided into high- or low-m1Ascore groups, and a significant survival difference was observed. External validation confirmed the prognostic value of the m1Ascore. A nomogram incorporating the m1Ascore and other clinicopathological factors was constructed and had good performance for predicting survival. Two agents, mitoxantrone and doxorubicin, were determined to be potential therapeutic drugs for the high-risk group. Conclusion This study provided novel insights into m1A modification and metabolic heterogeneity in cancer, promoted risk stratification in the clinic from the perspective of m1A modification, and further guided individual treatment strategies.
Background: This study is designed to evaluate the predictive value of derived monocyte to lymphocyte ratio (dMLR), neutrophil to lymphocyte ratio (NLR) and eosinophil to lymphocyte ratio (ELR) for lymph node metastasis (LNM) in gastric signet ring cell carcinoma (SRCC) patients. Methods: We carried out a retrospective analysis for 203 eligible patients who underwent radical gastrectomy between January 2011 and September 2020. Results: The diagnostic sensitivity and specificity for dMLR were 60.3% and 72.2%, respectively; while for NLR and ELR were 64.1% and 66.6%, and 91.6% and 23.6%, respectively. The dMLR and NLR were identified as independent predictors of LNM, but ELR was not. A nomogram was developed incorporating dMLR and clinical characteristics with AUC of 0.868, and the outcome of DCA supported good clinical benefit. Conclusions: dMLR is a promising novel preoperative biomarker to predict LNM of gastric SRCC.
Background Circular RNA (circRNA) plays a crucial role in non‐small cell lung cancer (NSCLC) progression. However, the role of circCCDC134 in NSCLC is still largely unknown. Methods Quantitative real‐time PCR was utilized for measuring circCCDC134, microRNA (miR)‐625‐5p and nuclear factor of activated T cell 5 (NFAT5) expression. Cell functions were evaluated by colony formation, EdU, transwell, and wound healing assays and flow cytometry. Glucose consumption, lactate production, and ATP level were determined to analyze cell glycolysis. Western blot analysis was used to detect protein expression. Animal experiments were performed to assess the effect of circCCDC134 on NSCLC tumor growth. RNA interaction was evaluated by dual‐luciferase reporter assay and RIP assay. Exosomes were isolated from the serum of NSCLC patients and healthy normal controls. Results Highly expressed circCCDC134 was found in NSCLC tissues and cells, as well as in the serum exosomes of NSCLC patients. Downregulated circCCDC134 restrained NSCLC cell growth, metastasis and glycolysis. CircCCDC134 sponged miR‐625‐5p to regulate NFAT5. MiR‐625‐5p inhibitor abolished the regulation of circCCDC134 knockdown on NSCLC progression, and NFAT5 overexpression eliminated the effects of miR‐625‐5p on NSCLC cell behaviors. CircCCDC134 knockdown also inhibited NSCLC tumor growth. Conclusion Our study revealed that circCCDC134 was involved in regulating NSCLC progression through the miR‐625‐5p/NFAT5 pathway, confirming that circCCDC134 might function as the diagnostic and therapeutic target for NSCLC.
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