Kallikrein-11, in Association with Coiled-Coil Domain Containing 25, as a Potential Prognostic Marker for Cholangiocarcinoma with Lymph Node Metastasis

Molecules. 2021 May 22;26(11):3105. doi: 10.3390/molecules26113105.

Abstract

Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes. Currently, the treatment and prognosis for CCA are mostly poor. Recently, we have reported that coiled-coil domain containing 25 (CCDC25) protein level in the sera may be a diagnostic marker for CCA. Subsequently, we identified three binding proteins of CCDC25 and found that kallikrein-11 (KLK11) expression was highest among those binding proteins. In this study, we investigated CCDC25 and KLK11 expression in CCA and adjacent normal tissues (n = 18) using immunohistochemistry. The results demonstrated that the expressions of CCDC25 and KLK11 in CCA tissues were both significantly higher than the adjacent tissues (p < 0.001 and p = 0.001, respectively). Then, using GEPIA bioinformatics analysis, KLK11 mRNA was significantly overexpressed in CCA tumor tissues compared with normal tissues (p < 0.05). Moreover, CCDC25 expression was positively correlated with KLK11 expression in CCA with lymph node metastasis (p = 0.028, r = 0.593). An analysis for the interaction of KLK11 with CCDC25 and other proteins, using STRING version 11.0, revealed that CCDC25 and KLK11 correlated with metastasis-related proteins. In addition, Kaplan-Meier survival curve analysis revealed that a high expression of KLK11 was associated with the poor prognosis of CCA. In conclusion, KLK11 is, as a binding protein for CCDC25, possibly involved in the metastatic process of CCA. KLK11 may be used as a prognostic marker for CCA.

Keywords: CCDC25; KLK11; cholangiocarcinoma; immunohistochemistry; prognostic marker.

MeSH terms

  • Biomarkers, Tumor / blood*
  • Cell Line, Tumor
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / pathology
  • Computational Biology
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ligands
  • Lymphatic Metastasis*
  • Membrane Proteins / blood*
  • Neoplasm Metastasis
  • Prognosis
  • Protein Binding
  • Protein Domains
  • Protein Interaction Mapping
  • Serine Endopeptidases / blood*
  • Signal Transduction

Substances

  • Biomarkers, Tumor
  • CCDC25 protein, human
  • Ligands
  • Membrane Proteins
  • trypsin-like serine protease
  • Serine Endopeptidases