Abstract 2504: In-depth proteome quantification of hepatocellular carcinoma tissues reveals significant liver dysfunction
Authors: Yexiong Tan, Fangjun Wang, Hanfa Zhou, Hongyang Wang
Journal: Cancer Research (2014)

Abstract Hepatocellular carcinoma (HCC) is one of the most fatal cancers world-wide. Comparing with genome analyses, in-depth proteome quantification of HCC liver tissues is still inadequate. In this study, we combined both stable isotope labeling and multiple reaction monitoring label-free strategies for in-depth proteome quantification of both pooled and individual liver tissues with or without carcinoma. Among the 2,759 and 1,788 reliably quantified proteins by labeling and label-free methods, 266 significantly changed proteins showed consistent dysregulation trends in both pooled and individual tissues. We demonstrated that these proteins are widely involved in different biological processes of carcinoma progression. And many essential processes, such as protein synthesis and degradation, xenobiotic toxic substances and alcohol metabolisms and so on, are significantly dysregulated. For example, 6 members of eIF family, eukaryotic translation initiation factor 2/3/4/6 (EIF2S2, EIF3D, EIF3I, EIF3J, EIF4A1 and EIF6); 4 members of 40S ribosomal subunit, ribosomal protein 7/11/12/20 (RPS7, RPS11, RPS12 and RPS20); and 3 members of 60S ribosomal subunit, ribosomal protein L12/P0/P2 (RPL12, RPLP0 and RPLP2) are reliably quantified in our study, and all of them are significantly up-regulated in both pooled and individual proteome quantification, which implies that the protein synthesis is activated during the progress of HCC. Besides, various molecules for protein degradation, 2 members of Ubiquitin-like modifier activating enzyme, ie. E1 and E2; ubiquitin-like modifier activating enzyme 1 (UBA1) and ubiquitin-conjugating enzyme E2L 3 (UBE2L3); 10 members of proteasome, proteasome 26S subunit alpha type 4/5/7 (PSMA4, PSMA5 and PSMA7), beta type 2/9 (PSMB2 and PSMB9), ATPase 3 (PSMC3), non-ATPase 2/5/11 (PSMD2, PSMD5 and PSMD11), and proteasome activator subunit 1 (PSME1); and 10 members of heat shock proteins, heat shock 10 kDa protein (HSPE1), 27 kDa protein (HSPB1), DnaJ (Hsp40) homolog (DNAJB11), 60 kDa protein (HSPD1), 70 kDa protein 4/5/8/9 (HSPA4, HSPA5, HSPA8 and HSPA9), and 90 kDa proteins (HSP90AA1 and HSP90AB1) are all significantly up-regulated in both pooled and individual proteome quantification . Therefore, the protein degradation processes are also activated in HCC liver tissue The upstream regulators for the 266 significantly dysregulated proteins in both pooled and individual proteome quantification were analyzed. Finally, 15 and 9 upstream regulators were predicted in the activated and inhibited states, respectively. And the regulation trends of most of the proteins are consistent with the states of upstream regulators. 7 genes of the 15 activated up-stream regulators, MYC, MYCN, NFE2L2, CEBPB, HIF1A, SATB1 and XBP1, are transcription factors Note: This abstract was not presented at the meeting. Citation Format: Yexiong Tan, Fangjun Wang, Hanfa Zhou, Hongyang Wang. In-depth proteome quantification of hepatocellular carcinoma tissues reveals significant liver dysfunction. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2504. doi:10.1158/1538-7445.AM2014-2504