Dickkopf-related protein 1, a new biomarker for local immune status and poor prognosis among patients with colorectal liver Oligometastases: a retrospective study

BMC Cancer. 2019 Dec 12;19(1):1210. doi: 10.1186/s12885-019-6399-1.

Abstract

Background: It was reported that tumor-expressed dickkopf-related (DKK) proteins affect micro-environment. However, the influence of DKK1 on colorectal cancer (CRC) liver oligometastases (CRCLOM) remains unclear.

Methods: CRC cases after resection of liver oligometastases were enrolled in Sun Yat-Sen University Cancer Center with intact clinical data. Serum DKK1 was detected by ELISA assay. Immunofluorescent staining examination for CD3 and CD8 in slices were also conducted.

Results: Among 65 patients included, the recurrence-free survival (RFS) and overall survival (OS) were significantly better in the low serum DKK1 group (RFS: P = 0.021; OS: P = 0.043). DKK1 was overexpressed in stage IV CRC patients in TCGA data. The number of CD8+ tumor-infiltrating lymphocytes (TILs) in invasive margin of CRC liver oligometastases was significantly higher in low serum DKK1 group (P = 0.042).

Conclusion: Elevated serum DKK1 level was associated with poorer RFS and OS, and less CD8+ TILs in invasive margin in CRC liver oligometastases. DKK1 might serve as a supplementalprognostic factor for clinical risk score and a potential target for immunotherapy.

Keywords: Colorectal cancer; DKK1; Immune status; Liver oligometastases.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / immunology
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood
  • Intercellular Signaling Peptides and Proteins / immunology*
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins