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Research Project

Molecular characterization of Alpha 1-Antitrypsin deficiency-related liver cancer

Principal Investigator:
Marion Bouchecareilh
Center:
Bordeaux
City/Country:
Bordeaux, France
Start date:
March 2024
Status:
Ongoing
Contact E-mail:
marion.bouchecareilh@ibgc.cnrs.fr
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Introduction

Liver cancer is markedly increased in PiZZ individuals, who are known to develop invasive hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) on cirrhosis and non-cirrhosis livers. Overall, these finding suggest that Z mutant could induce or participate in one or multiple specific carcinogenesis pathways. However, nothing is known about the molecular mechanisms of AATD-related liver cancer.

Objectives

The main objective is to determine the specific molecular signature of AATD-related liver cancer and decipher the molecular mechanism of the Z variant and its potential co-factors in AATD carcinogenesis

Inclusion criteria

Formalin-fixed and paraffin-embedded (FFPE) liver tissues (tumoral and non-tumoral) from PiZZ patients presenting a liver cancer (hepatocellular carcinoma and Cholangiocarcinoma) without other causes of chronic liver diseases known (alcohol, hepatitis, NASH, other genetic diseases).

Brief summary

We propose to identify genes, proteins and related cellular pathways specifically deregulated in AATD-related liver cancer. Thus, Whole Genome Sequencing (WGS), RNA-sequencing (RNA-seq) and mass spectrometry (LC/MS) will be performed on DNA, RNA and proteins extracted from formalin-fixed, paraffin embedded (FFPE) liver samples from PiZZ subjects, presenting liver cancer (HCC and CCA). Next, the genetic, transcriptomic and proteomic profiles of these AATD-related liver cancer will be analyzed and the molecular signatures of these cancers will be resolved by bioinformatic tools. In order to determine the specificity of this AATD-related liver cancer signature, this latter will be compared to publicly available dataset and also to the Oncoprot platform (https://www.tbmcore.cnrs.fr/oncoprot/) HCC proteomic database.