Identification and Comparison of Differentiation-Related Proteins in Hepatocellular Carcinoma Tissues by Proteomics

Abstract

Histological differentiation is a major pathological criterion indicating the risk of tumor invasion and metastasis in patients with hepatocellular carcinoma. The degree of tumor differentiation is controlled by a complex interacting network of associated proteins. The principal aim of the present study is to identify the possible differentiation-related proteins which may be used for early diagnosis and more effective therapies. We compared poorly differentiated and well-differentiated hepatocellular carcinoma tissues by using 2-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Among the 11 identified protein spots, 6 were found to be upregulated in poorly differentiated hepatocellular carcinoma tissues and 5 were correspondingly downregulated. Immunohistochemistry was performed on 106 hepatocellular carcinoma tissues to confirm the results of the proteomic analysis. By using bioinformatic tools GO and STRING, these proteins were found to be related to catalytic activity, binding, and antioxidant activity. In particular, our data suggest that overexpression of peroxiredoxin-2, annexin A2, and heat shock protein β-1 was correlated with tumor invasion, metastasis, and poor prognosis, and therefore, these proteins may serve as potential diagnostic and therapeutic biomarkers.

Peroxiredoxin2 downregulation enhances hepatocellular carcinoma proliferation and migration, and is associated with unfavorable prognosis in patients

“…However, the clinical importance and function of PRDX2 in HCC has not been comprehensively studied. A previous study conducted in our laboratory illustrated upregulation of PRDX2 in poorly differentiated HCC tissues by proteomic approaches and indicated the involvement of PRDX2 in HCC progression (18). Notably, in our present study, our results revealed the protein expression levels of PRDX2 in HCC tissues were relatively lower than that of their adjacent normal liver tissues, not only in all 4 matched tissue specimens, but also in the protein microarrays which were comprised of 176 paired tissue spots.…”

“…According to our recently published research study led by Zhao et al , using 2-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, 11 different proteins were identified from 10 poorly differentiated HCC tissues and 10 well differentiated HCC tissues, among which PRDX2 was found to be upregulated in poorly differentiated HCC tissues compared to the well differentiated HCC tissues. Using bioinformatics tools, it was revealed that PRDX2 may be correlated with tumor invasion, metastasis, and poor prognosis, thus serving as a potentially useful diagnostic and therapeutic biomarker (18). However, whether the expression level of PRDX2 has clinical significance in HCC patients has yet to be reported.…”

Development and validation of nomograms for predicting prognosis in patients with solitary HCC: A TRIPOD-Compliant study

“…The differentiation of HCC was associated with prognosis. The lower the degree of tumor differentiation pathologically, the higher the protein expression of invasion and metastasis, which were related to poor prognosis [ 24 ]. Another study proved that a poorly differentiated tumor hurt the recurrence and long-term survival of solitary HCC [ 25 ].…”

Microphysiological vascularized solid tumor model for drugs and cell therapies screening

“…7G-I). Relative to the tumor regions, ECM regions overexpressed genes involved in ECM protein production (COL1A1, COL1A2, COL6A3, COL3A1, SERPINH1), associated with HCC (THBS1, ANXA1, APP, CD44, LTBP1, HSPB1) [38, [41][42][43][44][45][46], HBV-associated HCC (HLA-E, HLA-C, THY1) [47][48][49][50][51][52][53], and vasculature formation (THBS1, ENG, CDH5, ROBO4) [54] (Fig. 7G).…”