Background Increasing evidence has shown that circular RNAs (circRNAs) are involved tumourigenesis and metastasis of hepatocellular carcinoma (HCC); however, progression about its function in HCC is relatively slow. Here, we aimed to investigate whether plasma circRNAs could reflect the tumour-infiltrating lymphocytes (TILs) in HCC tumour tissues and serve as prognosis biomarker for HCC.
Methods Tissue samples of patients with HCC were subjected to immunohistochemistry staining against CD8 to examine the TILs. Then, we investigated the expression profile of circRNAs by microarray between plasma of patients with HCC with high TILs and low TILs, and the differentially expressed circRNAs were validated with qRT-PCR. Statistical analysis was performed with SPSS software and GraphPad Prism.
Results We have demonstrated that patients with HCC with high TILs exhibit a significant better overall survival, suggesting clinical outcome could be predicted by TILs. Global circRNA microarray between plasma of patients with HCC with high TILs and low TILs successfully identified six differentially expressed novel circRNAs. Among them, the expression of hsa_circ_0064428 was significantly reduced in patients with HCC with high TILs but increased in patients with low TILs. Moreover, hsa_circ_0064428 was negatively correlated with patient’s survival, tumour size and metastasis.
Conclusion These findings together imply that hsa_circ_0064428 could be considered as a potential HCC prognosis biomarker. Future in-depth research is required to further illustrate the involvement of hsa_circ_0064428 in HCC tumourigenesis and metastasis.
- hepatocellular carcinoma
- circular rnas
- tumor infiltrating lymphocytes
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QW and MC contributed equally.
Contributors Conception and design: JJ and X-MX. Provision of study materials or patients: QW, MC and JJ. Collection and assembly of data: ML, Y-FZ and GS. Data analysis and interpretation: WF and QW. Manuscript writing: QW, X-MX and JJ. Final approval of manuscript: all authors.
Funding This study was supported by the National Natural Science Foundation of China (no. 81573657), Key Research and Development Project of Zhejiang Province (no. 2018C03024), Zhejiang Province Medical and Health Care Key Project (no. 2016146810), National Natural Science Foundation of Zhejiang Province (no. LQ17H180001), Chinese Medicine Science and Technology Projects of Zhejiang Province (nos. 2015ZA228 and 2016ZA209), Key Discipline Project of Lishui City (2017ZDXK07), National Natural Science Foundation of Zhejiang Province (nos. LQ16H160019 and LQ17H180001), High-Level Talent Project of Lishui City (2014RC01), Science and Technology Department of Lishui City (2017ZDXK07), and Experimental Animal Science and Technology Projects of Zhejiang Province (2016C37101).
Competing interests None declared.
Patient consent Obtained.
Ethics approval Affiliated Lishui Hospital of Zhejiang University.
Provenance and peer review Not commissioned; externally peer reviewed.