Exosomes as potential diagnosis and treatment for liver cancer

Table 1 Potential biomarkers for liver cancer

Exosomal content	Sample	Expression	Isolation of exosomes	Content detection	Function	Ref.		Direction
HCC
Proteins
ANGPT2	Serum (n = 93)	Up	SBI	Immunoblotting and ELISA	Induces tumor angiogenesis	[14]	Potential targets
mRNAs
hnRNPH1	Serum (n = 223)	Up	Total exosome isolation reagent (Thermo Fisher Scientific Co.)	qRT-PCR	Associated with the Child–Pugh classification, portal vein tumor emboli, lymph node metastasis, TNM stage, and OS	[15]
LDH-C4	Serum (n = 212)	Up	exoRNeasy Serum/Plasma Midi Kit (Qiagen)	qRT-PCR	Related to treatments and recurrence prediction of HCC patients	[16]
miRNAs
miR-10b-5p	Serum (n = 37)	Up	Ultracentrifugation	qRT-PCR	Respectively, associated with early diagnosis and prognosis of HCC	[17]
miR-1247-3p	Serum (n = 135)	Up	Ultracentrifugation	qRT–PCR	Shows a positive correlation with lung metastasis in HCC patients	[18]	Potential targets
miR-125b	Serum (n = 218)	Up	SBI	qRT-PCR	Discriminate HCC patients with a high risk of recurrence and poor prognosis	[19]
miR-182	Serum and ascitic fluid	Up	exoRNeasy Serum/Plasma Midi Kit (Qiagen)	qRT-PCR	Up-regulated in NASH-induced liver cirrhosis with HCC compared to NASH-induced liver cirrhosis without HCC	[20]
miR-21	Serum (n = 79)	Up	SBI	qRT-PCR	Related to TNM stage and other prognostic factors	[21]
	Plasma (n = 150)	Up	SBI	qRT-PCR	Significantly higher in patients with HCC compared with cirrhotic patients and the control group	[22]
	Serum (n = 90)	Up	Total Exosome Isolation Reagent (Invitrogen)	qRT-PCR	Positively correlated with cirrhosis and tumor stage	[23]
	Serum (n = 95)	Up	Ultracentrifugation	qRT–PCR	Shows a positive correlation with survival in HCC patients	[24]	Potential targets
miR-215-5p	Serum (n = 37)	Up	Ultracentrifugation	qRT-PCR	Respectively, associated with early diagnosis and prognosis of HCC	[17]
miR-224	Serum (n = 139)	Up	Total Exosome Isolation Kit	qRT–PCR	Related to tumor size and differentiate HCC patients from healthy controls	[25]	Potential targets
miR23-a/b	Serum (n = 50)	Up	Ultracentrifugation	qRT–PCR	A promising target for future treatment of HCC	[26]	Potential targets
miR-301a	Serum and ascitic fluid (n = 52)	Up	exoRNeasy Serum/Plasma Midi Kit (Qiagen)	qRT-PCR	Up-regulated in NASH-induced liver cirrhosis with HCC compared to NASH-induced liver cirrhosis without HCC	[20]
miR-373	Serum and ascitic fluid (n = 52)	Up	exoRNeasy Serum/Plasma Midi Kit (Qiagen)	qRT-PCR	Up-regulated in NASH-induced liver cirrhosis with HCC compared to NASH-induced liver cirrhosis without HCC	[20]
miR-4661-5p	Serum (n = 720)	Up	SBI	qRT-PCR	Associated with the prognosis of patients with HCC	[27]
miR-638	Serum (n = 54)	Up	Ultracentrifugation	qRT–PCR	Promising for surveillance of HCC recurrence	[28]	Potential targets
miR-665	Serum (n = 40)	Up	SBI	qRT–PCR	Associated with tumor size, invasion, and clinical stage of HCC patients	[29]	Potential targets
miR-92a-3p	Plasma (n = 42)	Up	Ultracentrifugation	qRT–PCR	Shows a positive correlation with metastasis in HCC patients	[30]	Potential targets
miR-92b	Serum (n = 121)	Up	SBI	qRT-PCR	Prediction of posttransplant HCC early recurrence	[31]
miR-93	Serum (n = 108)	Up	Total Exosome Isolation Reagent (Invitrogen)	qRT–PCR	Correlated with stage, tumor size and predict patients' survival rate of HCC patients	[32]	Potential targets
miRNA-96	Plasma (n = 150)	Up	SBI	qRT-PCR	Significantly higher in patients with HCC compared with cirrhotic patients and the control group	[22]
lncRNAs
lncRNA-ATB	Serum (n = 79)	Up	SBI	qRT-PCR	Related to TNM stage and other prognostic factors	[21]
DANCR	Serum (n = 183)	Up	SBI	Digital droplet PCR (DDPCR)	Positively associated with HCV-HCC recurrence	[33]
lncRNA FAL1	Serum (n = 60)	Up	SBI	qRT-PCR	Play an oncogenic role in HCC	[34]	Potential targets
lnc-FAM72D-3	Serum (n = 180)	Up	Ultracentrifugation	qRT-PCR	Functions as an oncogene in HCC	[35]	Potential targets
lncRNA Jpx	Plasma (n = 100)	Up	SBI	qRT-PCR	Promising biomarkers for female patients with HCC	[36]
LINC00161	Serum (n = 112)	Up	Total Exosome Isolation Kit (Invitrogen)	qRT-PCR	A significant prediction of tumor growth and metastasis in HCC	[37]
	Serum (n = ?)	Up	-	qRT-PCR	Promote HCC tumorigenesis	[38]	Potential targets
lncRNA-RP11-583F2.2	Serum (n = 120)	Up	exoRNeasy Serum/Plasma Midi Kit (Qiagen)	qRT-PCR	Up-regulated in the serum of hepatocellular carcinoma patients as compared with hepatitis C virus patients and normal good health control	[39]
ENSG00000248932.1 ENST00000440688.1 ENST00000457302.2	Serum (n = 600)	Up	SBI	qRT-PCR	Potential fingerprints for the tumorigenesis prediction	[40]
circRNAs
circ_0070396	Plasma (n = 273)	Up	exoEasy Maxi Kit (QIAGEN)	qRT-PCR	Discriminate HCC individuals from patients with chronic hepatitis B and liver cirrhosis	[41]
circAKT3	Serum (n = 224)	Up	SBI	qRT-PCR	Associated with HCC recurrence and mortality	[42]
circ-DB	Plasma (n = 40)	Up	Ultracentrifugation	qRT-PCR	Promote the tumor growth	[43]	Potential targets
circPTGR1	Serum (n = 129)	Up	SBI	qRT-PCR	Promote HCC progression	[44]	Potential targets
circUHRF1	Serum (n = 643)	Up	SBI	qRT-PCR	Drive resistance to anti-PD1 immunotherapy	[45]	Potential targets
HB
miRNAs
miR-21	Serum (n = 64)	Up	SBI	qRT-PCR	Significantly higher in patients with HB	[46]

Up: Upregulated; SBI: Exo-Quick exosome precipitation solution; HCC: Hepatocellular carcinoma; HB: Hepatoblastoma; qRT-PCR: Quantitative reverse transcription polymerase chain reaction.