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

Abstract

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.

The Combination of Arginine Deprivation and 5-Fluorouracil Improves Therapeutic Efficacy in Argininosuccinate Synthetase Negative Hepatocellular Carcinoma

“…We used an arbitrary below- and above-average value which may not be perfect, but has the advantage adjacent benign tissue for comparison thus decreasing variation attributable to technical factors. Interestingly, review of the available literature on the ASS gene shows that the majority of studies support the notion that few if any ASS expressing tumors are highly proliferative [40,42]. It is noteworthy that ASS also has been proposed as a tumor suppressor gene [43].…”

Pioglitazone-mediated reversal of elevated glucose metabolism in the airway epithelium of mouse lung adenocarcinomas

“…Solute carrier family 37 member 4 (SLC37A4) regulates glucose-6-phosphate (G6P) transport from the cytoplasm to the lumen of the endoplasmic reticulum in order to maintain glucose homeostasis and is a prognostic biomarker for ovarian cancer (32). UDP-glucose pyrophosphorylase 2 (UDP-UGP2) encodes the enzyme important for glucose synthesis, and its expression has been found to be associated with poor outcome of a number of cancers (33,34). Dipeptidyl peptidase 4 (DPP4) functions as an ectopeptidase that can inactivate incretins, catalyze the cleavage of chemokines, promote cell migration, and activate lymphocytes; its expression is linked to the carcinogenesis of many malignant tumors (35).…”

Quantification of free polyamines and their metabolites in biofluids and liver tissue by UHPLC-MS/MS: application to identify the potential biomarkers of hepatocellular carcinoma

“…As a convenient and quick method, biomarker inspection has gained much more attention. Alpha fetal protein (AFP) as a biomarker with high molecular weight is currently used in the surveillance of HCC, but the upward trend can be detected only after HCC progression [2]. Consequently, other biomarkers which can predict the presence of HCC at the early stage are highly desired.…”