N6-methyladenosine regulators in hepatocellular carcinoma: investigating the precise definition and clinical applications of biomarkers

肝细胞癌中的 N6-甲基腺苷调节剂:研究生物标志物的精确定义和临床应用

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作者:Xiaokai Yan #, Yao Qi #, Xinyue Yao #, Lulu Yin, Hao Wang, Ji Fu, Guo Wan, Yanqun Gao, Nanjing Zhou, Xinxin Ye, Xiao Liu, Xing Chen

Background

Accurately identifying effective biomarkers and translating them into clinical practice have significant implications for improving clinical outcomes in hepatocellular carcinoma (HCC). In this study, our

Conclusions

Our findings suggest that the mutual validation of big data analysis and functional experiments may facilitate the precise identification and definition of biomarkers, and our m6A risk models may have the potential to guide personalized chemotherapy, targeted treatment, and immunotherapy decisions in HCC.

Methods

Concentrating on the N6-methyladenosine (m6A) modification regulators, we utilized dozens of multi-omics HCC datasets to analyze the expression patterns and genetic features of m6A regulators. Through the integration of big data analysis with function experiments, we have redefined the biological roles of m6A regulators in HCC. Based on the key regulators, we constructed m6A risk models and explored their clinical value in estimating prognosis and guiding personalized therapy for HCC.

Results

Most m6A regulators exhibit abnormal expression in HCC, and their expression is influenced by copy number variations (CNV) and DNA methylation. Large-scale data analysis has revealed the biological roles of many key m6A regulators, and these findings are well consistent with experimental results. The m6A risk models offer significant prognostic value. Moreover, they assist in reassessing the therapeutic potential of drugs such as sorafenib, gemcitabine, CTLA4 and PD1 blockers in HCC. Conclusions: Our findings suggest that the mutual validation of big data analysis and functional experiments may facilitate the precise identification and definition of biomarkers, and our m6A risk models may have the potential to guide personalized chemotherapy, targeted treatment, and immunotherapy decisions in HCC.

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