J Liver Cancer.  2022 Mar;22(1):30-39. 10.17998/jlc.2022.02.25.

Diagnostic performance of serum exosomal miRNA-720 in hepatocellular carcinoma

Affiliations
  • 1Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 2The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 3Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea

Abstract

Background
/Aim: Hepatocellular carcinoma (HCC) is associated with poor prognosis, largely due to late detection. Highly accurate biomarkers are urgently needed to detect early-stage HCC. Our study aims to explore the diagnostic performance of serum exosomal microRNA (miR)-720 in HCC.
Methods
Exosomal miRNA was measured via quantitative real-time PCR. A correlation analysis of exosomal miR-720 and tumor or clinico-demographic data of patients with HCC was performed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of serum exosomal miR-720 for HCC, in comparison with α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II).
Results
MiR-720 was chosen as a potential HCC marker via miR microarray based on significant differential expression between tumor and non-tumor samples. Serum exosomal miR-720 was significantly upregulated in patients with HCC (n=114) versus other liver diseases (control, n=30), with a higher area under the ROC curve (AUC=0.931) than the other markers. Particularly, serum exosomal miR-720 showed superior performance in diagnosing small HCC (< 5 cm; AUC=0.930) compared with AFP (AUC=0.802) or PIVKA-II (AUC=0.718). Exosomal miR-720 levels showed marginal correlation with tumor size. The proportion of elevated miR-720 also increased with intrahepatic tumor stage progression. Unlike AFP or PIVKA-II showing a significant correlation with aminotransferase levels, the exosomal miR-720 level was not affected by aminotransferase levels.
Conclusions
Serum exosomal miR-720 is an excellent biomarker for the diagnosis of HCC, with better performance than AFP or PIVKA-II. Its diagnostic utility is maintained even in small HCC and is unaffected by aminotransferase levels.

Keyword

Hepatocellular carcinoma; Exosome; MicroRNA; Biomarkers; Diagnosis

Figure

  • Figure 1 Identification of exosomes. (A) Characterization of exosomes isolated from patient samples by transmission electron microscopy. Scale bar, 100 nm. (B) Western blot analysis of exosome markers, CD63 and HSP70, in serum exosomes. HCC, hepatocellular carcinoma.

  • Figure 2 Diagnostic performance of serum Exo miR-720 for HCC. (A) Serum Exo miR-720 levels in HCC and non-HCC patients. Comparison of the receiver operating characteristic curve of Exo miR-720, AFP, and PIVKA-II for diagnosis of (B) the overall HCC cases and (C) small HCC cases measuring less than 5 cm in diameter. Exo, exosomal; HCC, hepatocellular carcinoma; AUC, area under the receiver operating characteristic curves; AFP, α-fetoprotein; PIVKA-II, prothrombin-induced by vitamin K absence or antagonist-II.

  • Figure 3 Exo miR-720 levels according to HCC characteristics. (A) Correlation between Exo miR-720 and the size of HCC. Comparison of Exo miR-720 levels according to (B) tumor number and (C) intrahepatic HCC stage. (D) The proportion of high Exo miR-720 levels in different intrahepatic HCC stages. Exo, exosomal; HCC, hepatocellular carcinoma.

  • Figure 4 Exo miR-720 levels based on demographic characteristics of patients with HCC stratified by (A) age, (B) etiology of HCC, and (C) CTP class. Differences in correlation between each marker and (D) AST and (E) ALT levels. Exo, exosomal; HCC, hepatocellular carcinoma; HBV, hepatitis B virus; HCV, hepatitis C virus; NBNC, non-HBV non-HCV; CTP, Child-Turcotte-Pugh; AST, aspartate aminotransferase; ALT, alanine aminotransferase.


Reference

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