Despite its limitations, serum AFP still remains the most widely used tumor marker in clinical practice. Recent research favors the circulating hepatoma-specific AFP subfraction AFP-L3 and DCP over AFP alone in differentiating HCC from nonmalignant hepatopathy and detecting small HCC. Furthermore, some other tumor markers, such as GPC3, GGT II, AFU, have been shown to be supplementary to AFP and DCP in the detection of HCC. Some of them even can be detected in HCC patients seronegative for both AFP and DCP, thus indicating that the simultaneous determination of these markers may improve the accuracy.
However, most exciting and promising area of research in this disease has been the identification of a new group of molecules called miRNAs. MiRNAs have been discovered to be aberrantly expressed in HCC, and some of them are functionally involved in HCC carcinogenesis and progression. Furthermore, certain microRNAs are associated with HCC or related to HCC subtypes, implicating the potential use of microRNAs in HCC patient stratification of diagnosis and prognosis. Some of these HCC-associated miRNAs have been validated in independent cohorts. This brings the possibility of developing clinically useful platforms to develop HCC diagnosis, risk assessment, and patient risk stratification with the ultimate goal of personalized therapy.