Novel Proteomic Biomarker Panel for Prediction of Aggressive Metastatic Hepatocellular Carcinoma Relapse in Surgically Resectable Patients

The
natural course of early HCC is unknown, and its progression
to intermediate and advanced HCC can be diverse. Some early stage
HCC patients enjoy prolonged disease-free survival, whereas others
suffer aggressive relapse to stage IV metastatic cancer within a year.
Comparative proteomics of HCC tumor tissues was carried out using
2D-DIGE and MALDI-TOF/TOF MS to identify proteins that can distinguish
these two groups of stage I HCC patients. Twelve out of 148 differentially
regulated protein spots were found to differ by approximately 2-fold
for the relapse versus nonrelapse patient tissues. Four proteins,
namely, heat shock 70 kDa protein 1, argininosuccinate synthase, isoform
2 of UTP-glucose-1-phosphate uridylyltransferase, and transketolase,
were shown to have the potential to differentiate metastatic relapse
(MR) from nonrelapse (NR) HCC patients after validation by western
blotting and immunohistochemical assays. Subsequent TMA analysis revealed
a three marker panel of HSP70, ASS1, and UGP2 to be statistically
significant in stratifying the two groups of HCC patients. This combination
panel achieved high levels of sensitivity and specificity, which has
potential for clinical use in identifying HCC tumors prone to MR.
This stratification will allow development of clinical management,
including close follow-up and possibly treatment options, in the near
future.