Differential proteomic analysis of hepatocellular carcinoma

Abstract

Abstract. The principal aim of the present study consisted in the identification of the disregulated proteins associated with the development of hepatocellular carcinoma (HCC). The differences in protein expression between hepatocellular carcinoma (HCC) and the corresponding non-HCC liver tissues were investigated in a cohort of 20 patients using twodimensional fluorescence difference in gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). The upand down-regulated protein spots that exhibited 1.5-fold difference signal intensity with statistical significance (p<0.05, t-test, confidence intervals 95%) were excised from the gel and identified by peptide mass fingerprinting using matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Thirty-six protein spots corresponding to 29 different disregulated proteins, belonging to heterogeneous metabolic pathways, have been identified. Down-regulated proteins (n=23) were found superior in number than the up-regulated proteins (n=6). Detoxification, carbohydrate metabolism and amino acid biotrasformation represented the main disregulated pathways in HCC. Upregulation of aldo-keto reductase 1C2, thioredoxin and transketolase, involved in metabolic and regulatory cellular processes including proliferation, differentiation and carcinogenesis were remarkable. These proteins could represent useful biomarkers to provide new insights into global pathophysiologic changes of HCC and for the development of new pharmacological approaches to HCC therapy.

Proteomic Differences Between Hepatocellular Carcinoma and Nontumorous Liver Tissue Investigated by a Combined Gel-based and Label-free Quantitative Proteomics Study

“…In particular, the proteomics-based approach has turned out to be a promising one, offering several quantification techniques to reveal differences in protein expression that are caused by a particular disease. In most studies, the well-established 2D-DIGE technique has been applied for protein quantification followed by identification via mass spectrometry (7)(8)(9)(10)(11)(12)(13)(14)(15). Even if the quantification is very accurate and sensitive in this gel-based approach, the relatively high amount of protein sample necessary for protein identification is the major disadvantage of this technique.…”

Decreased Selenium-Binding Protein 1 Enhances Glutathione Peroxidase 1 Activity and Downregulates HIF-1α to Promote Hepatocellular Carcinoma Invasiveness

“…Resistance toward cytotoxic chemotherapy also affects survival and prognosis in patients with HCC (23). We and other groups have found that the expression of SBP1 is decreased in most HCCs and is associated with poor outcomes (13), but the possible molecular mechanism of SBP1 in HCC biology, particularly in cancer invasion and metastasis, has not been studied. Given the relationship among SBP1, GPX1, HIF-1a, and oxidative stress in the HCC microenvironment, in this study, we aimed to explore the role of SBP1 in cancer invasion and metastasis.…”

“…Decreased SBP1 was found in a vast number of human cancers, such as colorectal cancer (9), lung adenocarcinomas (10), ovarian cancer (11), gastric cancer (12), and hepatocellular carcinoma (HCC; ref. 13). However, the molecular mechanism underlying the tumor suppressive functions of SBP1 remains unclear.…”

An Integrative Proteomics and Interaction Network-Based Classifier for Prostate Cancer Diagnosis

“…Two-dimensional difference gel electrophoresis (2D-DIGE) technology, using a mixed-sample internal standard, is now recognized as an accurate method to determine and quantify human proteins, reducing inter-gel variability and simplifying gel analysis [5]. Several groups including our own have adopted this high throughput approach to evaluate the global expression of proteins in several human cancers, including hepatocellular carcinoma (HCC) [6], colorectal cancer [7], esophageal squamous cell carcinoma [8], breast cancer [9], ovarian cancer [10], bladder Cancer [11], PCa [12], [13] and pancreatic cancer [14]. However, there have been the large number of candidate proteins identified using high throughput platforms and it is lack of consistency among different detection systems because of the heterogeneity of the patient cohorts and the difference in platforms.…”