Poster Presentation 35th Lorne Cancer Conference 2023

High preoperative levels of circulating SFRP5 predict better prognosis in colorectal cancer patients (#225)

Runhao Li 1 2 , Saifei Liu 1 2 , Chandra Kirana 1 3 , Doan T Ngo 4 , Markus Trochsler 3 , Peter Hewett 3 , Richard Stubbs 5 , Ehud Hauben 1 3 , Kevin Aaron Fenix 1 3 , Guy Maddern 1 3 , Timothy Price 1 2 6 , Eric Smith 1 2 6
  1. Adelaide Medical School , The University of Adelaide, Adelaide , SA, Australia
  2. Solid tumour group, Basil Hetzel Institute for Translational Health Research, Woodville South, South Australia, Australia
  3. Department of Surgery, The Queen Elizabeth Hospital, Adelaide , SA, Australia
  4. School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia
  5. The Wakefield Clinic for Gastrointestinal Diseases, The Wakefield Clinic, Wellington, New Zealand
  6. Medical Oncology Group, The Queen Elizabeth Hospital, Adelaide , SA, Australia

Introduction: Aberrant Wnt signalling is a common feature in colorectal cancer (CRC). Secreted Frizzled-Related Protein 5 (SFRP5) is an adipokine known to inhibit Wnt signalling and is commonly silenced in CRC. This study investigated the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in CRC.

Methods: Plasma from CRC patients (n=162) and patients undergoing cholecystectomy (n=30), or surgical removal of the bowel for benign polyps or diverticulitis without pathological evidence of CRC (n=16) collected from The Queen Elizabeth Hospital (Adelaide, Australia) or Wakefield Hospital (Wellington, New Zealand), were analysed for preoperative cSFRP5 concentration by ELISA.  

Results: cSFRP5 was significantly higher in CRC compared with controls (p<0.001). Area under the receiver operating characteristic curve (AUROC) comparing the control group to CRC was 0.837 (95%CI:0.730–0.944; p<0.0001). A threshold plasma SFRP5 concentration of 28 ng/mL was associated with 63% (95%CI: 54–70%) sensitivity and 85% (95%CI: 72–92%) specificity. A threshold plasma SFRP5 concentration of 38 ng/mL was associated with 48% (95%CI: 40–56%) sensitivity and 93% (95%CI: 83–98%) specificity. In CRC, cSFRP5 was significantly associated with lower vascular invasion (p=0.001) and liver metastasis (p=0.016). Survival analysis demonstrated that low plasma SFRP5 (defined as <28 ng/ml) was associated with significantly shorter disease-free survival with univariate (hazard ratio: 3.672; 95%CI: 1.183–11.50; p=0.024) and multivariate analysis when the confounders stage and vascular invasion were considered (hazard ratio: 2.385; 95%CI: 1.181–4.816; p=0.015). These findings indicate the prognostic value of SFRP5 in CRC. The cSFRP5 findings will be validated in an independent cohort of 733 plasma samples from the Victorian Cancer Biobank, consisting healthy donors (n=100 males and n=100 females), benign polyps (n=84), and 449 CRC patients with stage I (n=148), II (n=100), III (n=100) and IV (n=101) disease.

Conclusion: Our findings suggest a role of cSFRP5 as a physiologic tumour suppressor and demonstrate its potential diagnostic and prognostic value in CRC.