Prognosis and personalized treatment prediction in TP53-mutant hepatocellular carcinoma: an in silico strategy towards precision oncology.

Publisher: Oxford University Press Country of Publication: England NLM ID: 100912837 Publication Model: Print Cited Medium: Internet ISSN: 1477-4054 (Electronic) Linking ISSN: 14675463 NLM ISO Abbreviation: Brief Bioinform Subsets: MEDLINE

Publication: Oxford : Oxford University Press
Original Publication: London ; Birmingham, AL : H. Stewart Publications, [2000-

Carcinoma, Hepatocellular*/drug therapy ; Carcinoma, Hepatocellular*/genetics ; Carcinoma, Hepatocellular*/metabolism ; Carcinoma, Hepatocellular*/mortality ; Liver Neoplasms*/drug therapy ; Liver Neoplasms*/genetics ; Liver Neoplasms*/metabolism ; Liver Neoplasms*/mortality ; Mutation* ; Precision Medicine* ; Tumor Suppressor Protein p53*/genetics ; Tumor Suppressor Protein p53*/metabolism; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage; Computer Simulation ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Imidazoles/administration & dosage ; Irinotecan/administration & dosage ; Male ; Naphthoquinones/administration & dosage ; Survival Rate

TP53 mutation is one of the most common genetic changes in hepatocellular carcinoma (HCC). It is of great clinical significance to tailor specialized prognostication approach and to explore more therapeutic options for TP53-mutant HCCs. In this study, a total of 1135 HCC patients were retrospectively analyzed. We developed a random forest-based prediction model to estimate TP53 mutational status, tackling the problem of limited sample size in TP53-mutant HCCs. A multi-step process was performed to develop robust poor prognosis-associated signature (PPS). Compared with previous established population-based signatures, PPS manifested superior ability to predict survival in TP53-mutant patients. After in silico screening of 2249 drug targets and 1770 compounds, we found that three targets (CANT1, CBFB and PKM) and two agents (irinotecan and YM-155) might have potential therapeutic implications in high-PPS patients. The results of drug targets prediction and compounds prediction complemented each other, presenting a comprehensive view of potential treatment strategy. Overall, our study has not only provided new insights into personalized prognostication approaches, but also thrown light on integrating tailored risk stratification with precision therapy.
(© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Keywords: TP53; hepatocellular carcinoma; precision medicine; prognosis

0 (Imidazoles)
0 (Naphthoquinones)
0 (TP53 protein, human)
0 (Tumor Suppressor Protein p53)
7673326042 (Irinotecan)
UZ77T1VFBM (sepantronium)

Date Created: 20200814 Date Completed: 20211122 Latest Revision: 20220722

20221213

10.1093/bib/bbaa164

32789496