Upregulated and downregulated proteins in hepatocellular carcinoma: a systematic review of proteomic profiling...

Hepatocellular carcinoma (HCC) has been a major clinical challenge due to low early diagnosis rate and poor prognosis. The aim of this systematic review was to identify differentially expressed proteins as potential high-confidence biomarkers for HCC, by validating data on differentially expressed proteins reported by studies on HCC tissues. In our studies, objectives, search strategy, study selection criteria, data elements, methods for extraction, and methods for assessing study quality were defined. Published studies that compared the protein expression profiles of HCC with those of noncancer tissues were included in the review. Furthermore, a protein ranking system was used to assess the number of comparisons in agreement. Monte Carlo simulation was used to assess the overlap significance. A total of 16 proteomic studies were eligible for the systematic review in our study, which reported 1283 differentially expressed proteins in HCC (526 upregulated, 744 downregulated). Of these proteins, 27 proteins were identified as differentially expressed proteins with consistent directions of change in at least three studies; four were upregulated, and 23 downregulated. One upregulated protein, heat-shock 70-kDa protein, and four downregulated proteins, fructose-1,6-bisphosphatase 1, formiminotransferase cyclodeaminase, alcohol dehydrogenase, and fructose-bisphosphate aldolase B were identified as potential biomarkers for HCC. In addition, nine other differentially expressed proteins were reported, but with inconsistent directions for the changes of the differential expression. The amount of overlap was highly significant. Therefore, five candidate proteins were defined as potential biomarkers for HCC, which may have diagnostic, prognostic and therapeutic significance.