In:
Liver Cancer, S. Karger AG, Vol. 11, No. 2 ( 2022), p. 162-173
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Perihilar cholangiocarcinoma (pCCA) is a rare primary liver malignancy. Even in patients amenable to surgery, outcomes are often dismal. Here, we aimed to identify prognostic markers for patient outcomes by analyzing functionally relevant single-nucleotide polymorphisms (SNPs) in genes with a role in tumor inflammation and angiogenesis. We analyzed 11 polymorphisms in the inflammation-angiogenesis axis ( 〈 i 〉 VEGF, EGF, EGFR, IL-1b, IL-6, CXCL8 (IL-8), IL-10, CXCR1, HIF1A 〈 /i 〉 , and 〈 i 〉 COX2 〈 /i 〉 genes) for their prediction of tumor recurrence and survival in pCCA patients undergoing surgery in a curative intent. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Samples were obtained from 111 patients with pCCA undergoing liver resection in curative intent. DNA was extracted and analyzed using polymerase chain reaction-restriction fragment length polymorphism protocols and correlated with patients’ outcomes. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Out of the assessed variants, only the 〈 i 〉 CXCR1 〈 /i 〉 (also: interleukin-8-receptor alpha – 〈 i 〉 IL-8RA 〈 /i 〉 ) +860C & #x3e;G heterozygous polymorphism (rs2234671) was associated with decreased disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) (18/111 (16.2%), median DFS 14 months, log-rank 〈 i 〉 p 〈 /i 〉 = 0.007; median CSS 31 months, log-rank 〈 i 〉 p 〈 /i 〉 = 0.007; and median OS 6 months, log-rank 〈 i 〉 p 〈 /i 〉 = 0.002), compared to the GG genotype (92/111 (82.9%), median DFS 55 months, median CSS 63 months, and median OS 33 months). In the multivariate analysis, +860C & #x3e;G remained an independent prognostic factor for DFS (adjusted 〈 i 〉 p 〈 /i 〉 = 0.008), CSS (adjusted 〈 i 〉 p 〈 /i 〉 = 0.001), and OS (adjusted 〈 i 〉 p 〈 /i 〉 = 0.001). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Genetic variant of 〈 i 〉 CXCR1 〈 /i 〉 +860C & #x3e;G may serve as a molecular marker for DFS, CSS, and OS in patients undergoing curative-intent surgery for pCCA, indicating that the analysis of SNPs in genes involved in immune-mediated angiogenesis may help to identify patient subgroups at high risk for dismal oncological and overall outcome.
Type of Medium:
Online Resource
ISSN:
2235-1795
,
1664-5553
Language:
English
Publisher:
S. Karger AG
Publication Date:
2022
detail.hit.zdb_id:
2666925-0
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