Deciphering the immunological and prognostic features of hepatocellular carcinoma through ADP-ribosylation-related genes analysis and identify potential therapeutic target ARFIP2

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..

BACKGROUND: Hepatocellular carcinoma is one of the most common malignancies, and its prognosis and treatment outcome cannot be accurately predicted. ADP-ribosylation (ADPR) is a post-translationa modification of proteins involved in protein trafficking and immune response. Therefore, it is necessary to explore the ADPR-related genes associated with the prognosis and therapeutic efficacy of hepatocellular carcinoma treatments.

METHODS: We downloaded the data of hepatocellular carcinoma samples to identify ADPR-related genes as prognostic markers, and established a novel ADPR-related index (ADPRI) based on univariate and multivariate COX regression analyses. Patients' prognosis, clinical features, somatic variant, tumor immune microenvironment, chemotherapeutic response and immunotherapeutic response were systematically analyzed. Finally, the role of ARFIP2 in hepatocellular carcinoma cells was preliminarily explored in vitro.

RESULTS: The ADPRI consisting of four ADPR related genes (ARL8B, ARFIP2, PARP12, ADPRHL1) was established to be a reliable predictor of survival in patients with hepatocellular carcinoma and was validated using external datasets. Compared with the low ADPRI group, the high ADPRI group presented higher levels of mutation frequency, immune infiltration and patients in high ADPRI group benefit more from immune checkpoint inhibitor treatment. In addition, we predicted some natural small molecule drugs as potential therapeutic targets for hepatocellular carcinoma. Finally, Knockdown of ARFIP2 inhibits the proliferation and migration of hepatocellular carcinoma cells by inducing the G1/S phase cell cycle arrest in HCC cells.

CONCLUSIONS: The ADPRI can be used to accurately predict the prognosis and immunotherapeutic response of hepatocellular carcinoma patients and providing valuable insights for future precision treatment of patients with hepatocellular carcinoma.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:117

Enthalten in:

Cellular signalling - 117(2024) vom: 21. März, Seite 111073

Sprache:

Englisch

Beteiligte Personen:

Jiang, Fenfen [VerfasserIn]
Xu, Yan [VerfasserIn]
Jiang, Zhuang [VerfasserIn]
Hu, Bin [VerfasserIn]
Lv, Qing [VerfasserIn]
Wang, Zhiyong [VerfasserIn]

Links:

Volltext

Themen:

ADP-ribosylation
ARFIP2
ARFIP2 protein, human
Adaptor Proteins, Signal Transducing
Hepatocellular carcinoma
Immunotherapy efficacy
Journal Article
Prognosis
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 11.03.2024

Date Revised 22.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.cellsig.2024.111073

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM367913968