Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection.

HCC HCC recurrence liver resection loss of heterozygosity next-generation sequencing

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
29 Jan 2021
Historique:
received: 31 12 2020
revised: 21 01 2021
accepted: 25 01 2021
entrez: 12 2 2021
pubmed: 13 2 2021
medline: 13 2 2021
Statut: epublish

Résumé

Hepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to complement potentially predictive clinical and pathological factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis. 124 HCC patients, who underwent a primary hepatic resection from January 2016 to December 2019, were recruited for this study. Next-generation sequencing (NGS) analysis and allelic imbalance assessment in a case-control subgroup analysis were performed. A time-to-recurrence analysis was performed as well by means of Kaplan-Meier estimators. Cumulative number of HCC recurrences were 26 (21%) and 32 (26%), respectively, one and two years after surgery. Kaplan-Meier estimates for the probability of recurrence amounted to 37% (95% C.I.: 24-47) and to 51% (95% C.I.: 35-62), after one and two years, respectively. Multivariable analysis identified as independent predictors of HCC recurrence: hepatitis C virus (HCV) infection (HR: 1.96, 95%C.I.: 0.91-4.24, multiple alterations of cancer genes are associated with HCC progression. In particular, the evidence of a specific AI mutation presented in 20 patients seemed to have a protective effect on the risk of HCC recurrence.

Sections du résumé

BACKGROUND BACKGROUND
Hepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to complement potentially predictive clinical and pathological factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis.
METHODS METHODS
124 HCC patients, who underwent a primary hepatic resection from January 2016 to December 2019, were recruited for this study. Next-generation sequencing (NGS) analysis and allelic imbalance assessment in a case-control subgroup analysis were performed. A time-to-recurrence analysis was performed as well by means of Kaplan-Meier estimators.
RESULTS RESULTS
Cumulative number of HCC recurrences were 26 (21%) and 32 (26%), respectively, one and two years after surgery. Kaplan-Meier estimates for the probability of recurrence amounted to 37% (95% C.I.: 24-47) and to 51% (95% C.I.: 35-62), after one and two years, respectively. Multivariable analysis identified as independent predictors of HCC recurrence: hepatitis C virus (HCV) infection (HR: 1.96, 95%C.I.: 0.91-4.24,
CONCLUSIONS CONCLUSIONS
multiple alterations of cancer genes are associated with HCC progression. In particular, the evidence of a specific AI mutation presented in 20 patients seemed to have a protective effect on the risk of HCC recurrence.

Identifiants

pubmed: 33572904
pii: cancers13030518
doi: 10.3390/cancers13030518
pmc: PMC7866287
pii:
doi:

Types de publication

Journal Article

Langues

eng

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Auteurs

Salvatore Gruttadauria (S)

Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), University of Pittsburgh Medical Center (UPMC), 90127 Palermo, Italy.
Department of Surgery and Medical and Surgical Specialties, University of Catania, 95124 Catania, Italy.

Floriana Barbera (F)

Research Department, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), 90127 Palermo, Italy.

Pier Giulio Conaldi (PG)

Research Department, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), 90127 Palermo, Italy.

Duilio Pagano (D)

Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), University of Pittsburgh Medical Center (UPMC), 90127 Palermo, Italy.

Rosa Liotta (R)

Pathology Unit, Department of Diagnostic and Therapeutic Services, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), 90127 Palermo, Italy.

Enrico Gringeri (E)

Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35122 Padova, Italy.

Roberto Miraglia (R)

Radiology Unit, Department of Diagnostic and Therapeutic Services, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), 90127 Palermo, Italy.

Gaetano Burgio (G)

Department of Anesthesia and Intensive Care, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), 90127 Palermo, Italy.

Marco Barbara (M)

Research Department, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), 90127 Palermo, Italy.

Giada Pietrosi (G)

Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), University of Pittsburgh Medical Center (UPMC), 90127 Palermo, Italy.

Calogero Cammà (C)

Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy.

Fabrizio Di Francesco (F)

Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), University of Pittsburgh Medical Center (UPMC), 90127 Palermo, Italy.

Classifications MeSH