Table 1.

Relevant miRNA-based and epigenetic alterations, which prognostic impact in HCC patients needs to be tested or confirmed.

Molecular alteration	Clinical significance	REMARK recommendations*	Status†
mRNA based (gene signatures)¶
Poor-survival signature (186 genes)12Φ	Poor survival	OK	EV
EpCAM signature22	Poor survival	OK	EV
Venous metastasis signature38	Hepatic metastasis	OK	EV
Class A20 / Hepatoblast signature21	Poor survival	OK	IV, EV
G3 subclass19	Poor survival	-	IV, EV
miRNA-based
Down-regulation miR-26a26	Poor survival	OK	EV
20-miRNA signature31	Venous metastasis, overall survival	OK	EV
Down-regulation miR-12224	Poor survival	-	IV, EV
Down-regulation Let-7 members25	Early recurrence	-	IV, EV
Up-regulation miR-125a27	Better survival	-	IV, EV
19-miRNA signature30	Poor survival	-	IV, EV
Up-regulation miR-22128	Multinodularity; reduced time to recurrence	-	T, IV, EV
Up-regulation miR-92, miR-20, miR-1829	Poor differentiation	-	T, IV, EV
Epigenetics
Genome wide hypomethylation32	Tumor Progression, Survival	-	IV, EV
Hypermethilation of E-cadherin or GSTP135	Poor survival	-	IV, EV
Degree of hypomethylation33	Advanced histological grade; larger tumor size	-	T, IV, EV
264-gene hypermethylation profile34	Moderately/poor differentiated tumors	-	T, IV, EV
Hypermethilation of E-cadherin36	Microvascular invasion; tumor recurrence	-	T, IV, EV
Hypermethilation of RIZ137	Correlation with disease-free survival	-	T, IV, EV

^*Reasonable compliance with REMARK recommendations for tumor marker prognostic studies⁴⁴

^†Current status in terms of clinical implementation (T: need further preliminary prognostic evaluation, IV: lacks internal validation, EV: lacks external validation)

^¶Molecular classifications (mRNA-based) with prognostic impact are thoroughly discussed elsewhere^8,9,17

^ΦGenomic signature obtained from early HCC