{
  "abstract": "The fibroblast growth factor 21 (FGF21) – FGF receptor 1 (FGFR1) – beta klotho (KLB) pathway is an essential metabolic regulatory pathway shown also to be protective against development of hepatocellular carcinoma (HCC) in animal models of chronic liver disease. We investigated the protein expression of the key receptors FGFR1 and obligatory co-receptor beta klotho (KLB) in HCC, precancerous liver cirrhosis and non-diseased liver tissue correlated with overall survival in a North of Scotland cohort.Human liver tissue coded as HCC, liver cancer, liver cirrhosis (LC) and normal liver (NL) was accessed retrospectively through Grampian Biorepository from patients undergoing elective liver surgery between 2008 and 2018 at Aberdeen Royal Infirmary, Scotland, UK. A liver tissue/cancer microarray was constructed comprising of 32 HCC, 25 liver cirrhosis (LC) and 11 morphologically normal, non-diseased liver (NL) formalin fixed paraffin embedded (FFPE) samples in duplicate. Immunohistochemistry was undertaken using Dako Autostainer and staining intensity quantified using QuPath_0.3.2 software to generate an H score for each cell compartment, data presented as mean H score ± SEM.Median survival from HCC was 42.0 months, (95% CI 10.762–73.238). All HCC cases were BCLC stage 0 or A, as would be expected for resection. FGFR1 and KLB demonstrated immunogenicity in all samples. FGFR1 whole cell expression was significantly lower in HCC 192.4 ± 7.41 compared NL 250 ± 10.47 and LC 224.8 ± 8.86. Similarly, KLB H scores were lower in HCC 203.0 ± 8.58 vs NL 264.4 ± 9.24 and LC 233.5 ± 13.04. Mean overall survival of HCC with FGFR1 H score > 150 was 43.94 (28.99 – 58.90) months and greater in scores <150 at 88.00 (24.66 – 151.34), p=0.285. Conversely, in KLB strong KLB staining was associated with a longer overall survival at 65.98 (46.83–85.12) months compared 32.42 (11.59–53.24) months in negative/weak/moderate staining, p=0.006.Both LC and HCC had lower expression of FGFR1 and KLB, suggesting reduction in sensitivity to FGF21 in these. It likely reflects dedifferentiation of cancerous cells away from hepatocytes. Reduced FGFR1 tended to be associated with better outcomes, in line with recognised role of FGFR1 in cancers mediating other FGF mitotic activities. However, higher expression of KLB was associated with a significantly higher survival, since this dictates cellular sensitivity to FGF21, this may suggest maintenance of sensitivity to FGF21 is beneficial. KLB may have a role as biomarker predictive of outcome in HCC resection.",
  "authors": [
    {
      "affiliations": [
        "School of Medicine, Medical Sciences and Nutrition, University Of Aberdeen, Aberdeen, UK"
      ],
      "name": "Fiona Clegg"
    },
    {
      "affiliations": [
        "School of Medicine, Medical Sciences and Nutrition, University Of Aberdeen, Aberdeen, UK",
        "Grampian Biorepository, NHS Grampian, UK"
      ],
      "name": "Kristine Roberts"
    },
    {
      "affiliations": [
        "School of Medicine, Medical Sciences and Nutrition, University Of Aberdeen, Aberdeen, UK"
      ],
      "name": "Dawn Thompson"
    },
    {
      "affiliations": [
        "School of Medicine, University of Dundee, UK"
      ],
      "name": "Mairi Mclean"
    },
    {
      "affiliations": [
        "School of Medicine, Medical Sciences and Nutrition, University Of Aberdeen, Aberdeen, UK"
      ],
      "name": "Mirela Delibegovic"
    },
    {
      "affiliations": [
        "School of Medicine, Medical Sciences and Nutrition, University Of Aberdeen, Aberdeen, UK",
        "Grampian Biorepository, NHS Grampian, UK"
      ],
      "name": "Graeme Murray"
    }
  ],
  "title": "P52 Lower expression of beta klotho is associated with worse overall survival in hepatocellular carcinoma in North of Scotland cohort",
  "uid": "3ad5b952-262a-5d80-afc5-eb3cc01a4b95"
}