Tumor endothelial ELTD1 as a predictive marker for treatment of renal cancer patients with sunitinib

BMC Cancer. 2020 Apr 22;20(1):339. doi: 10.1186/s12885-020-06770-z.


Background: Patients with metastatic renal cell cancer (mRCC) are commonly treated with the tyrosine kinase inhibitor sunitinib, which blocks signalling from vascular endothelial growth factor (VEGF) - and platelet-derived growth factor-receptors, inhibiting development of new blood vessels. There are currently no predictive markers available to select patients who will gain from this treatment. Epidermal growth factor, latrophilin and seven transmembrane domain-containing protein 1 (ELTD1) is up-regulated in tumor endothelial cells in many types of cancer and may be a putative predictive biomarker due to its association with ongoing angiogenesis.

Methods: ELTD1, CD34 and VEGF receptor 2 (VEGFR2) expressions were analysed in tumor vessels of renal cancer tissues from 139 patients with mRCC using immunohistochemistry. Ninety-nine patients were treated with sunitinib as the first or second-line therapy. Early toxicity, leading to the termination of the treatment, eliminated 22 patients from the analyses. The remaining (n = 77) patients were included in the current study. In an additional analysis, 53 sorafenib treated patients were evaluated.

Results: Patients with high ELTD1 expression in the tumor vasculature experienced a significantly better progression free survival (PFS) with sunitinib treatment as compared to patients with low ELTD1 expression (8 versus 5.5 months, respectively). The expression level of CD34 and VEGFR2 showed no correlation to sunitinib response. In sorafenib treated patients, no association with ELTD1 expression and PFS/OS was found.

Conclusions: Our results identify tumor vessel ELTD1 expression as a positive predictive marker for sunitinib-treatment in patients suffering from mRCC. The negative results in the sorafenib treated group supports ELTD1 being a pure predictive and not a prognostic marker for sunitinib therapy.

Keywords: ELTD1; Predictive marker; Renal cancer; Tissue microarray; Tyrosine kinase inhibitor.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD34 / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / secondary*
  • Endothelial Cells / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, G-Protein-Coupled / metabolism*
  • Retrospective Studies
  • Sunitinib / therapeutic use*
  • Survival Rate
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • ADGRL4 protein, human
  • Antigens, CD34
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Receptors, G-Protein-Coupled
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • Sunitinib