Published online Jan 7, 2020. doi: 10.3748/wjg.v26.i1.86
Peer-review started: September 2, 2019
First decision: October 14, 2019
Revised: December 4, 2019
Accepted: December 13, 2019
Article in press: December 13, 2019
Published online: January 7, 2020
Processing time: 126 Days and 10.8 Hours
Hepatocellular carcinoma (HCC) is among the deadliest conditions worldwide. One of the challenges related to HCC is the identification of specific and sensitive diagnostic and prognostic biomarkers. MicroRNAs have been shown to be deregulate in HCC and microRNA-122 (miR-122) is among the most promising liver-specific molecules.
miR-122 has been studied in Asian-Pacific regions but only limited knowledge is available from European population. At present the role of miR-122 as prognostic is not independently validated. Most importantly, it is still less known about potential factors that may influence miR-122 level in blood samples.
Circulating miR-122 may be influenced by impaired renal function, alpha-fetoprotein (AFP) and hemoglobin concentration. Those factors may strongly influence the performance of miR-122 a potential biomarker in HCC.
A cohort of well characterized patients with HCC were included in this study. Quantitative TaqMan assay was used to analyze miR-122 in serum and the results were normalized to spiked-in cel-miR-39. The data were stratified based on individual characteristics including liver disease, liver biochemistry, tumor staging and overall survival.
Overall miR-122 was shown to be independent to Child-Pugh score, Barcelona clinic liver cancer tumor staging classification or etiology of liver disease. Among the studied factors, we identified alanine aminotransferase, aspartate aminotransferase, AFP and renal function (creatinine) as factors that may influence miR-122 level in serum. According to our results, low miR-122 may be associated with lower overall survival, however, only if certain conditions including cirrhosis score, tumor stage or APF are considered.
The results from this study strongly suggest that renal function and liver inflammation may impact microRNA biomarkers. In particular, a liver-specific miR-122 may be strongly influenced by intrahepatic inflammation which may create potential bias. Our results support the use of miR-122 as a marker for liver inflammation. The value of miR-122 in prediction of overall survival is, however, limited due to the co-existing factors. Further studies will need to determine the mechanism responsible for the influence, but also find a way of controlling the influencing factors in biomarker studies.
This study clearly highlights the need for better understanding of microRNAs biogenesis in circulation. Since large number of studies focus on microRNAs as potential biomarkers, we urge for better characterization of co-existing factors to identify potential individual influencing factors. Future studies related to miR-122 need to consider also renal function and liver biochemistry.