Analysis of prognostic germline polymorphisms in patients with advanced hepatocellular carcinoma.
Hepatocellular carcinoma (HCC)
biomarkers
prognosis
single nucleotide polymorphisms (SNPs)
sorafenib
Journal
Translational gastroenterology and hepatology
ISSN: 2415-1289
Titre abrégé: Transl Gastroenterol Hepatol
Pays: China
ID NLM: 101683450
Informations de publication
Date de publication:
2023
2023
Historique:
received:
14
03
2023
accepted:
25
08
2023
medline:
29
11
2023
pubmed:
29
11
2023
entrez:
29
11
2023
Statut:
epublish
Résumé
The prognosis of hepatocellular carcinoma (HCC) is influenced by both tumor and patient specific factors. Current therapies of advanced HCC target angiogenesis and immune evasion, however there are no clinically useful biomarkers to guide clinicians. Our aim in this retrospective cohort study was to validate single nucleotide polymorphisms (SNPs) prognostic of outcome in advanced HCC from the literature, and to analyze exploratory SNPs chosen from evaluation of the HCC tumor immune microenvironment. Using a database of patients with HCC treated with sorafenib, blood samples were genotyped, clinical variables were retrospectively collected, and SNPs were analyzed for association with progression-free survival (PFS) and overall survival (OS). A subsequent analysis was conducted to determine if identified SNPs were prognostic in trans arterial chemoembolization (TACE) treated patients. Literature review identified 7 SNPs in vascular endothelial growth factor (VEGF), eNOS, angiopoietin 2 (ANGPT2) and vascular endothelial growth factor receptor 2 (VEGFR2), however none were externally validated in our dataset. Of the 35 exploratory immunomodulatory SNPs, the following were associated with PFS or OS: CCL2 C-C motif ligand 2 (CCL2) (rs1024611), interleukin-10 ( SNPs identified by literature review to be prognostic in sorafenib treated patients with advanced HCC were not validated in our dataset. Our findings suggest potentially important prognostic implications of SNPs in VEGFR2, CCL2, IL-10, CTLA-4 and NFKB1 that deserve further study.
Sections du résumé
Background
UNASSIGNED
The prognosis of hepatocellular carcinoma (HCC) is influenced by both tumor and patient specific factors. Current therapies of advanced HCC target angiogenesis and immune evasion, however there are no clinically useful biomarkers to guide clinicians.
Methods
UNASSIGNED
Our aim in this retrospective cohort study was to validate single nucleotide polymorphisms (SNPs) prognostic of outcome in advanced HCC from the literature, and to analyze exploratory SNPs chosen from evaluation of the HCC tumor immune microenvironment. Using a database of patients with HCC treated with sorafenib, blood samples were genotyped, clinical variables were retrospectively collected, and SNPs were analyzed for association with progression-free survival (PFS) and overall survival (OS). A subsequent analysis was conducted to determine if identified SNPs were prognostic in trans arterial chemoembolization (TACE) treated patients.
Results
UNASSIGNED
Literature review identified 7 SNPs in vascular endothelial growth factor (VEGF), eNOS, angiopoietin 2 (ANGPT2) and vascular endothelial growth factor receptor 2 (VEGFR2), however none were externally validated in our dataset. Of the 35 exploratory immunomodulatory SNPs, the following were associated with PFS or OS: CCL2 C-C motif ligand 2 (CCL2) (rs1024611), interleukin-10 (
Conclusions
UNASSIGNED
SNPs identified by literature review to be prognostic in sorafenib treated patients with advanced HCC were not validated in our dataset. Our findings suggest potentially important prognostic implications of SNPs in VEGFR2, CCL2, IL-10, CTLA-4 and NFKB1 that deserve further study.
Identifiants
pubmed: 38021355
doi: 10.21037/tgh-23-22
pii: tgh-08-23-22
pmc: PMC10643180
doi:
Types de publication
Journal Article
Langues
eng
Pagination
32Informations de copyright
2023 Translational Gastroenterology and Hepatology. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-22/coif). BHL reports grants, honoraria, and meeting support from Astrazeneca, and grants from Pfizer. DC reports grants, honoraria, or advisory board support from NCI, CIHR, CCSRI, Astrazeneca, Takeda, Boehringer Ingelheim, AMGEN, EMD Serono, Pfizer, Jazz, Merck, Abvie, Anheart, Roche, BMS, and Novartis. GL reports grants, honoraria, or advisory board support from NCI, CIHR, CCSRI, Astrazeneca, Takeda, Boehringer Ingelheim, AMGEN, EMD Serono, Pfizer, Jazz, Merck, Abvie, Anheart, Roche, BMS, and Novartis. The other authors have no conflicts of interest to declare.
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