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

Abstract

Background 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.

A Review of the Use of Extracellular Vesicles in the Treatment of Neonatal Diseases: Current State and Problems with Translation to the Clinic

“…Firstly, the selection of an appropriate source from which to obtain EVs with high therapeutic efficacy is a key aspect influencing the efficacy of the therapy. While previous research primarily focused on MSCs as a primary tool in regenerative medicine and as a source of EVs, [ 239 ] more recent studies have broadened the spectrum of potential EV sources. Encouraging prospects are offered by milk [ 227 ] and non-animal-derived EVs [ 120 , 121 ].…”

“…Although the existence of EVs and their potential therapeutic applications are known and some molecular mechanisms underlying their therapeutic effects have been explored ( Figure 3 ), the exact identity and composition of the therapeutic components in these EVs are still not fully understood. The role of specific non-coding RNAs (such as piRNA, ribosomal RNA, small nuclear and nucleolar RNAs and circular RNAs) is not fully elucidated, and the functions of double-stranded DNA in EVs remain to be determined [ 239 , 240 , 241 ]. This knowledge gap hinders the full exploitation of the therapeutic potential of EVs and the optimization of their clinical efficacy.…”

Extracellular Vesicles as Delivery Vehicles for Non-Coding RNAs: Potential Biomarkers for Chronic Liver Diseases

“…PiRNAs enclosed in EVs could develop into useful diagnostic biomarkers to distinguish, for instance, HCC patients from non-tumor ones. In this context, Rui et al compared, using small RNA sequencing, serum EVs (exosomes) derived from 125 HCC patients and 44 non-tumor controls [ 161 ]. Five differentially expressed piRNAs (piR-15254, piR-1029, piR-35395, novel-piR-32132, and novel-piR-43597) were present at significantly higher levels in the HCC samples with respect to the controls, which when combined presented a superior AUROC (area under the receiver operating characteristic) with respect to the single piRNAs, revealing the potential diagnostic value of this piRNA signature in the detection of HCC, including that with low tumor burden.…”

Extracellular Vesicles in Hepatocellular Carcinoma: Progress and Challenges in the Translation from the Laboratory to Clinic

“…The expression levels of tRNA-ValTAC-3, tRNA-GlyTCC-5, tRNA-ValAAC-5, and tRNA-GluCTC5 were significantly higher in the plasma EVs of HCC patients compared with healthy donors, suggesting that plasma EV tsRNAs could serve as new diagnostic biomarkers. A recent study [ 55 ] used high-throughput sequencing technology to analyze the expression levels of PIWI-interacting RNAs (piRNAs) in serum EVs from 15 HCC patients and 15 controls. The findings from this analysis showed significant differential expression of piRNAs in serum EVs among HCC patients, indicating five possible biomarkers for the diagnosis of HCC.…”