Abstract 1967P
Background
Survival problems in hepatocellular carcinoma (HCC) challenge the clinical practice, and drug resistance is one of the major obstacles. Microvascular invasion (MVI) is a histological feature of HCC related to aggressive biological behavior. Its influence on sorafenib sensitivity has been reported. But the mechanism was unclear. This study aimed to investigate the regulatory mechanisms and functional roles of lncRNAs as ceRNAs in MVI genesis, HCC progression, and sorafenib resistance.
Methods
We systematically studied the RNA-seq data of HCC. First established an MVI related network of dysregulated ceRNAs. Then, developed a lncRNA signature with prognostic lncRNAs. Finally, HCC’s sensitivity to sorafenib was tested by this lncRNA signature with an extensive bioinformatics method.
Results
An MVI related deregulated ceRNA network consisting of 13 lncRNAs, three miRNAs, and two mRNAs was constructed. A risk score system based on four prognostic lncRNAs (AC002511.1, ARHGEF7-AS1, ATP2B2-IT1, and ZNF385D-AS1) was developed as a lncRNA signature, which showed good discrimination and predictive ability for OS. Deep data mining into pharmacology dataset shew lncRNA signature score was positively related to sorafenib IC50 (Rho=0.2, P=0.005); additionally, multivariant logistics confirmed our lncRNA signature score was an independent risk factor for sorafenib resistance (OR=1.94, P=0.03).
Conclusions
MVI related lncRNAs signature could be a prognostic biomarker for HCC and might contribute to sorafenib resistance. Targeted the 4 lncRNAs in our study might improve the efficacy of sorafenib. Moreover, this “ceRNA network-lncRNA prognostic signature-sorafenib resistance” approach to investigating the mechanism concealed between MVI and sorafenib narrowed the scope of target lncRNAs, but also gave a hint to drug resistance research, which will help expand our understanding of the ceRNA mechanisms involved in the early development of MVI and sorafenib resistance in HCC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Xinyu Bi and Zhiwen Luo.
Funding
The state key project on infection diseases of China (Grant No. 2018ZX10723204-005-003).
Disclosure
All authors have declared no conflicts of interest.