Serum Exosome-Derived piRNAs Could Be Promising Biomarkers for HCC Diagnosis

Tao Rui,1,2 Kai Wang,1,2 Aizhai Xiang,1 Jufeng Guo,1 Ning Tang,1 Xin Jin,1 Yimou Lin,3 Jian Liu,1 Xiaobing Zhang1,2 1Department of Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Key Laboratory of Integrated Oncology and Intelligent Medicine of ZheJiang Province, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 3Department of Surgery, Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University Hangzhou, Hangzhou, 310003, People’s Republic of ChinaCorrespondence: Tao Rui; Xiaobing Zhang, Email 11818248@zju.edu.cn; 11818341@zju.edu.cnBackground: Serum exosome-based liquid biopsy has significant advantages for screening and diagnosing hepatocellular carcinoma (HCC). P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are novel small silencing RNAs that have been identified to function in cancer-related signalling pathways. However, studies on the presence of piRNAs in serum exosomes from HCC patients and their diagnostic values in HCC are not well reported. Our aim is to validate serum exosome-derived piRNAs as the valuable component of liquid biopsy for diagnosing HCC.Methods: We used small RNA (sRNA) sequencing to profile piRNAs from serum exosomes and describe the base distribution characteristics of serum exosome-derived piRNAs. Serum exosomes from 125 HCC patients and 44 nontumor donors were included in this study.Results: We found that piRNAs were components of serum exosomes from HCC patients. A total of 253 differentially expressed serum exosome-derived piRNAs were screened from HCC compared with the piRNAs from nontumor donors. Serum exosome-derived piRNAs from HCC displayed a distinctive base distribution. To further confirm the potential diagnostic value of serum exosome-derived piRNAs in HCC, we detected the levels of the top 5 upregulated piRNAs in our Chinese cohort. The training set and validation set both showed that all 5 piRNAs were dramatically increased in the serum exosomes from HCC compared with the piRNAs from non-tumour donors. The piRNAs could strongly identify HCC patients from non-tumour donors according to the area under the receiver operating characteristic (AUROC) model. Additionally, the piRNAs could also present significant values for the diagnosis of HCC with low tumour burden.Conclusion: piRNAs enriched the components of serum exosomes from HCC and could serve as promising biomarkers for HCC diagnosis.Keywords: biomarker, exosome, sRNA-seq, HCC, piRNA