Proteomic signature corresponding to alpha fetoprotein expression in liver cancer cells

Abstract

Alpha fetoprotein (AFP) has been implicated in the development of hepatocellular carcinoma and is considered to be a diagnostic and prognostic tumor marker. Because elevated expression of AFP is associated with many characteristics of hepatocellular carcinoma tissues, we hypothesized that multiple proteins may function in a coordinated manner with AFP. To identify such proteins, we performed global protein expression analysis, namely a proteomic study. The protein expression profiles of 9 AFP-producing liver cancer cell lines (JHH-5, HuH-1, PLC/PRL/5, Hep3B, HT-17, JHH-7, HuH-7, HepG2, Li-7) and 7 nonproducing liver cancer cell lines ( H epatocellular carcinoma (HCC) represents the vast majority of liver cancer, accounting for more than 90% of all primary liver cancers, and ranks fifth in frequency among all malignancies worldwide. 1,2 Infection with hepatitis B or C virus has been identified as an etiological factor, and the subsequent cellular and histological changes leading to HCC have been extensively studied. 3 Genetic alterations, including loss of heterozygosity 4,5 and aberrant DNA methylation, 6 also have been implicated in the carcinogenesis of HCC. Nevertheless, the outcome for HCC patients still remains dismal, partly because of the difficulty in establishing an early diagnosis and the frequent recurrence and intrahepatic metastasis after surgery. 7 Although systematic chemotherapy for unresectable HCC has been widely used, its efficacy remains low and complications such as significant myelosuppression are observed during the course of treatment. 8 Serum alpha fetoprotein (AFP) has been considered to be a hallmark of development of HCC. 9 Serum AFP alone has a limited role in the early diagnosis of HCC, because a considerable proportion of HCC patients do not have elevated serum AFP, and serum AFP can increase in patients with diseases other than HCC; it may, however, be a useful prognostic indicator, because the median survival rate of HCC patients with markedly elevated AFP was significantly shorter than that of patients with normal or moderately elevated AFP. 10 AFP is a multifunctional glycoprotein belonging to the family of albumin-like proteins. 11 AFP has been shown to serve as a dual regulator of growth in a multitude of cell types and cancers involving

Two‐dimensional gel electrophoresis as tool for proteomics studies in combination with protein identification by mass spectrometry

“…Other cancer tissues were analyzed using proteome methods, such as of lung [91,92], liver [93], colon [77,94], bladder [95][96][97][98], heart [99] or prostate [100]. Srisomsap et al [101] detected upregulation of cathepsin B in neoplastic thyroid tissues by proteomic analysis.…”

“…The diverse functions of proteins and their appearance in various species of different modifications dictate their functional investigations and determine the type of cancer phenotype; on the level of DNA or RNA this is not possible. Hence, these signatures will be reflected as tumor markers to achieve personalized medicine (for details see [93,[128][129][130]). …”

Protein expression associated with early intrahepatic recurrence of hepatocellular carcinoma after curative surgery

“…1A). (22) In brief, a portion of all samples was mixed together to make an internal control sample, aliquoted and stored at −80°C until use. Fifty micrograms of both the internal control sample and each experimental sample were labeled with 200 nmol of 1-(5-carboxypentyl)-1′-propylindocarbocyamine halide (Cy3) and 1-(5-carboxypentyl)-1′-methylindocarbocyamine halide (Cy5) (GE Healthcare Bio-sciences, Little Chalfont, Buckinghamshire, UK), respectively.…”

“…(18)(19)(20)(21) To complement gene expression studies, global protein expression profiling, namely a proteomic approach, has been carried out for the study of HCC. (22)(23)(24)(25)(26)(27)(28) Conceptually, proteomics reflects the molecular background of cancer phenotypes more directly, as the final product of genetic and epigenetic events is the proteins contained in the cells.…”

Cancer: A proteomic disease

“…Multivariate analysis of six up-regulated and five down-regulated proteins was used to distinguish AFP-producing cell lines from non-AFP producing cell lines. Understanding their interaction could provide insight into the biology of AFP-producing hepatocellular carcinoma cells [33]. More than 50% of human cancers have a p53 gene mutation.…”