EPB41L5 is Associated With the Metastatic Potential of Low-grade Pancreatic Neuroendocrine Tumors

Cancer Genomics Proteomics. 2019 Sep-Oct;16(5):309-318. doi: 10.21873/cgp.20136.

Abstract

Background/aim: Low-grade pancreatic neuroendocrine tumors (LG-PNETs) behave unpredictably. The aim of the study was to identify biomarkers that predict PNET metastasis to improve treatment selection.

Patients and methods: Five patients with primary non-metastatic LG-PNETs, six with primary LG-PNETs with synchronous or metachronous metastases (M-PNETs), and six metastatic to liver LG-PNETs (ML-PNETs) from the group of six M-PNET patients were selected. RNA data were normalized using iterative rank-order normalization. Student's t-test identified differentially-expressed genes in LG-PNETs versus M-PNETs. A 2-fold difference in expression was considered to be significant. Results were validated with an independent dataset of LG-PNETs and metastatic LG-PNETs.

Results: Overall, 195 genes had a >2-fold change (in either direction). A total of 29 genes were differentially overexpressed in M-PNETs. Erythrocyte membrane protein band 4.1-like 5 (EPB41L5) had a 2.07-fold change increase in M-PNETs and the smallest p-value. EPB41L5 was not statistically different between M-PNETs and ML-PNETs. EPB41L5 differential expression between primary and metastatic LG-PNETs was confirmed by immunohistochemistry.

Conclusion: These results support further investigation into whether EPB41L5 is a biomarker of PNETs with high risk for metastases.

Keywords: EPB41L5; Pancreatic neuroendocrine tumor; gene expression profile; immunohistochemistry.

MeSH terms

  • Adult
  • Aged
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neuroendocrine Tumors / genetics
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / pathology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology

Substances

  • EPB41L5 protein, human
  • Membrane Proteins