Impact of Angiogenesis- and Hypoxia-Associated Polymorphisms on Tumor Recurrence in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection.
Hannah MillerZoltan CziganyIsabella LurjeSophie ReicheltJan BednarschPavel StrnadChristian TrautweinChristoph RoderburgFrank TackeNadine Therese GaisaRuth Knüchel-ClarkeUlf Peter NeumannGeorg LurjePublished in: Cancers (2020)
Tumor angiogenesis plays a pivotal role in hepatocellular carcinoma (HCC) biology. Identifying molecular prognostic markers is critical to further improve treatment selection in these patients. The present study analyzed a subset of 10 germline polymorphisms involved in tumor angiogenesis pathways and their impact on prognosis in HCC patients undergoing partial hepatectomy in a curative intent. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 127 HCC patients at a German primary care hospital. Genomic DNA was extracted, and genotyping was carried out using polymerase chain reaction (PCR)-restriction fragment length polymorphism-based protocols. Polymorphisms in interleukin-8 (IL-8) (rs4073; p = 0.047, log-rank test) and vascular endothelial growth factor (VEGF C + 936T) (rs3025039; p = 0.045, log-rank test) were significantly associated with disease-free survival (DFS). After adjusting for covariates in the multivariable model, IL-8 T-251A (rs4073) (adjusted p = 0.010) and a combination of "high-expression" variants of rs4073 and rs3025039 (adjusted p = 0.034) remained significantly associated with DFS. High-expression variants of IL-8 T-251A may serve as an independent molecular marker of prognosis in patients undergoing surgical resection for HCC. Assessment of the patients' individual genetic risks may help to identify patient subgroups at high risk for recurrence following curative-intent surgery.
Keyphrases
- vascular endothelial growth factor
- endothelial cells
- patients undergoing
- free survival
- primary care
- end stage renal disease
- prognostic factors
- newly diagnosed
- ejection fraction
- copy number
- healthcare
- peritoneal dialysis
- minimally invasive
- single molecule
- genome wide
- rectal cancer
- patient reported outcomes
- binding protein
- acute coronary syndrome
- dna methylation
- climate change
- coronary artery bypass
- circulating tumor
- human health
- adverse drug
- patient reported
- genetic diversity
- combination therapy