Establishment of a prognostic model based on m6A regulatory factors and stemness of hepatocellular carcinoma using RNA-seq data and scRNA-seq data

使用 RNA-seq 数据和 scRNA-seq 数据建立基于 m6A 调控因子和肝细胞癌干性的预后模型

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作者:Yan Liang #, Sen Chen #, Jinghe Xie #, Guanrong Yan, Tingting Guo, Tianyang Li, Shoupei Liu, Weiping Zeng, Shuai Zhang, Keqiang Ma, Honglin Chen, Yimeng Ou, Bailin Wang, Weili Gu, Yuyou Duan3

Background

Hepatocellular carcinoma (HCC) with high incidence and mortality is one of the most common malignant cancers worldwide. Increasing evidence has reported that N6-methyladenosine (m6A) modification has been considered as a major contribution to the occurrence and development of tumors. Method: In our study, we comprehensively analyzed the connection between m6A regulatory factors and cancer stem cells (CSCs) of HCC to establish a clinical tool for predicting its outcome. First, we concluded that the expression level of m6A regulatory factors was related with the stemness of hepatocellular carcinoma. Subsequently, we gained a ten hub regulatory factors that were associated with prognosis of hepatocellular carcinoma by overall survival (OS) analysis using ICGC and TCGA datasets, and these regulatory factors included YTHDF1, IGF2BP1, METTL3, IGF2BP3, HNRNPA2B1, IGF2BP2, RBM15B, HNRNPC, RBMX, and LRPPR. Next, we found that these ten hub m6A regulatory factors were highly expressed in CSCs, and CSCs related pathways were also enriched by the gene set variation analysis (GSVA). Then, correlation, consensus clustering and PCA analysis were performed to reveal potential therapeutic benefits of HCC. Moreover, univariate Cox regression (UNICOX), LASSON and multivariate Cox regression (MULTICOX) analyses were adopted to establish HCC prognosis prediction signature.

Conclusion

In summary, these ten hub regulatory factors would be useful therapeutic targets for HCC treatment, and RBM15B/LRPPRC/IGF2BP1/IGF2BP3 prognostic indicators can be used to guide therapy for HCC patients.

Results

Four regulatory factors RBM15B, LRPPRC, IGF2BP1, and IGF2BP3 were picked as valuable prognostic indicators.

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