Prognostic and immunological role of sulfatide-related lncRNAs in hepatocellular carcinoma

Frontiers in Oncology

Oncology

Xing Feng Huang¹  Li Sheng Fu²  Fei Fan³  Qian Qian Cai⁴ 

[1] Department of Biliary Tract Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China;Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, China;Department of The Second Ward of Special Treatment, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China;Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, China;

关键词: sulfatide;    lncRNAs;    HCC;    prognosis;    immune infiltration;   

DOI  :  10.3389/fonc.2023.1091132

 received in 2022-11-06, accepted in 2023-01-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundHepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Long non-coding RNAs (lncRNAs) play important roles in the occurrence and development of HCC through multiple pathways. Our previous study reported the specific molecular mechanism for sulfatide regulation of integrin αV expression and cell adhesion in HCC cells through lncRNA AY927503. Next, it is necessary to identify more sulfatide-related lncRNAs, explore their clinical signifcance, and determine new targeted treatment strategies.MethodsMicroarrays were used to screen a complete set of lncRNAs with different expression profiles in sulfatide-treated cells. Sulfatide-related lncRNAs expression data and corresponding HCC patient survival information were obtained from the The Cancer Genome Atlas (TCGA) database, and the prognosis prediction model was constructed based on Cox regression analysis. Methylated RNA immunoprecipitation with next generation sequencing (MeRIP-seq) was used to detemine the effect of sulfatide on lncRNAs m6A modification. Tumor Immune Estimation Resource (TIMER) and Gene set nnrichment analysis (GSEA) were utilized to enrich the immune and functional pathways of sulfatide-related lncRNAs.ResultsA total of 85 differentially expressed lncRNAs (|Fold Change (FC)|>2, P<0.05) were screened in sulfatide-treated HCC cells. As a result, 24 sulfatide-related lncRNAs were highly expressed in HCC tissues, six of which were associated with poor prognosis in HCC patients. Based on thses data, a sulfatide-related lncRNAs prognosis assessment model for HCC was constructed. According to this risk score analysis, the overall survival (OS) curve showed that the OS of high-risk patients was significantly lower than that of low-risk patients (P<0.05). Notably, the expression difference in sulfatide-related lncRNA NRSN2-AS1 may be related to sulfatide-induced RNA m6A methylation. In addition, the expression level of NRSN2-AS1 was significantly positively correlated with immune cell infiltration in HCC and participated in the peroxisome and Peroxisome proliferator-activated receptor (PPAR) signaling pathways.ConclusionsIn conclusion, sulfatide-related lncRNAs might be promising prognostic and therapeutic targets for HCC.

【 授权许可】

Unknown   
Copyright © 2023 Huang, Fu, Cai and Fan