Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma

Nature
Ying JiangChinese Human Proteome Project (CNHPP) Consortium

Abstract

Hepatocellular carcinoma is the third leading cause of deaths from cancer worldwide. Infection with the hepatitis B virus is one of the leading risk factors for developing hepatocellular carcinoma, particularly in East Asia1. Although surgical treatment may be effective in the early stages, the five-year overall rate of survival after developing this cancer is only 50-70%2. Here, using proteomic and phospho-proteomic profiling, we characterize 110 paired tumour and non-tumour tissues of clinical early-stage hepatocellular carcinoma related to hepatitis B virus infection. Our quantitative proteomic data highlight heterogeneity in early-stage hepatocellular carcinoma: we used this to stratify the cohort into the subtypes S-I, S-II and S-III, each of which has a different clinical outcome. S-III, which is characterized by disrupted cholesterol homeostasis, is associated with the lowest overall rate of survival and the greatest risk of a poor prognosis after first-line surgery. The knockdown of sterol O-acyltransferase 1 (SOAT1)-high expression of which is a signature specific to the S-III subtype-alters the distribution of cellular cholesterol, and effectively suppresses the proliferation and migration of hepatocellular carcinoma....Continue Reading

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Methods Mentioned

BETA
RNA-seq
GTPase
nuclear translocation
proteomic profiling
GTPases
nucleotide exchange
xenograft
acetylation
DNA Assay
PCR

Software Mentioned

DrGaP
R package cluster
maftools
Ensembl
ssGSEA
R package NMF
Progenesis QI
Cufflinks
COSMIC
GSVA

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