A Hypoxia-Related miRNA-mRNA Signature for Predicting the Response and Prognosis of Transcatheter Arterial Chemoembolization in Hepatocellular Carcinoma

Abstract

Purpose

Transcatheter arterial chemoembolization (TACE) is commonly used in the treatment of hepatocellular carcinoma (HCC). However, not all patients respond to this treatment. TACE typically leads to hypoxia in the tumor microenvironment. Therefore, we aimed to construct a prognostic model based on hypoxia-related differentially expressed microRNA (miRNAs) in hepatocellular carcinoma (HCC) and to investigate the potential target mRNAs for predicting TACE response.

Methods

The hypoxia-related miRNAs (HRMs) were identified in liver cancer cells, then global test was performed to further select the miRNAs which were associated with recurrence and vascular invasion. A prognostic model was constructed based on multivariate Cox regression analysis; qRT-PCR analysis was used to validate the differentially expressed miRNAs in HCC cell lines under hypoxic condition. We further identified the putative target genes of the miRNAs and investigate the relationship between the target genes and TACE response, immune cells infiltration.

Results

We established a HRMs prognostic model for HCC patients, containing two miRNAs (miR-638, miR-501-5p), the patients with high-HRMs score showed worse survival in discovery and validation cohort; qRT-PCR analysis confirmed that these two miRNAs are up-regulated in hepatoma cells under hypoxic condition. Furthermore, four putative target genes of these two miRNAs were identified (ADH1B, CTH, FTCD, RCL1), which were significantly associated with TACE response, immune score, immunosuppressive immune cells infiltration, PDCD1 and CTLA4.

Conclusion

The HCC-HRMs signature may be utilized as a promising prognostic factor and may have implications for guiding TACE and immune therapy.

Keywords:

• hypoxia
• miRNA
• signature
• hepatocellular carcinoma
• prognosis

Data Sharing Statement

The data supporting the findings of this study are available from the GEO database (https://www.ncbi.nlm.nih.gov/geo/).

Acknowledgments

The authors declare no potential conflicts of interest, and thank the GEO database for data availability.

Supplemental Information

Supplemental information for this article can be found online.

Disclosure

The authors declare no conflict of interest.

Additional information

Funding

This study was supported by National Natural Science Foundation of China (No. 82030117 and 82074203).