Abstract
Lysine acetylation is a vital post-translational modification (PTM) of proteins, which plays an important role in cancer development. In healthy human liver tissues, multiple non-histone proteins were identified with acetylation modification, however, the role of acetylated proteins in hepatocellular carcinoma (HCC) development remains largely unknown. Here we performed a quantitative acetylome study of tumor and normal liver tissues from HCC patients. Overall, 598 lysine acetylation sites in 325 proteins were quantified, and almost 59% of their acetylation levels were significantly changed. The differentially acetylated proteins mainly consisted of non-histone proteins located in mitochondria and cytoplasm, which accounted for 42% and 24%, respectively. Bioinformatics analysis showed that differentially acetylated proteins were enriched in metabolism, oxidative stress, and signal transduction processes. In tumor tissues, 278 lysine sites in 189 proteins showed decreased acetylation levels, which occupied 98% of differentially acetylated proteins. Moreover, we collected twenty pairs of tumor and normal liver tissues from HCC male patients, and found that expression levels of SIRT1 (p = 0.002), SIRT2 (p = 0.01), and SIRT4 (p = 0.045) were significantly up-regulated in tumor tissues. Over-expression of possibly accounted for the widespread deacetylation of non-histone proteins identified in HCC tumor tissues, which could serve as promising predictors of HCC. Taken together, our work illustrates abundant differentially acetylated proteins in HCC tumor tissues, and offered insights into the role of lysine acetylation in HCC development. It provided potential biomarker and drug target candidates for clinical HCC diagnosis and treatment.
Highlights
hepatocellular carcinoma (HCC) is one of the most common human cancer types and accounts for about 90% of primary liver cancer (El-Serag and Rudolph, 2007)
By comparison of these two studies, we found that about 31% of proteins with differential acetylation levels identified in our study were present in the previous study (Figure 1B)
It indicated that the spectrum of acetylated proteins was highly conserved in human liver tissues, and the proteins with aberrant acetylation levels in tumor tissues probably participated in HCC development
Summary
HCC is one of the most common human cancer types and accounts for about 90% of primary liver cancer (El-Serag and Rudolph, 2007). To explore effective biomarkers for HCC diagnosis at early stage, multiple kinds of omics studies have been performed with samples from HCC patients or HCC cell lines, such as genomics, transcriptomics, proteomics, metabolomics, and so on. These omics studies provided huge number of molecules including circulating tumor DNA (ctDNA), circulating miRNAs, proteins, and metabolites as biomarker candidates for clinical HCC diagnosis (Tang et al, 2016; Zhou et al, 2011; Dittharot et al, 2018; Gao et al, 2019). Clinical studies showed that the sensitivity and specificity of one protein marker was limited in detecting HCC at early stage (Sun et al, 2008)
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