Tumor Biology

, Volume 37, Issue 5, pp 6349–6358

Diagnostic marker signature for esophageal cancer from transcriptome analysis

  • Ute Warnecke-Eberz
  • Ralf Metzger
  • Arnulf H. Hölscher
  • Uta Drebber
  • Elfriede Bollschweiler
Original Article

DOI: 10.1007/s13277-015-4400-4

Cite this article as:
Warnecke-Eberz, U., Metzger, R., Hölscher, A.H. et al. Tumor Biol. (2016) 37: 6349. doi:10.1007/s13277-015-4400-4

Abstract

Esophageal cancer is often diagnosed at an advanced stage. Diagnostic markers are needed for achieving a cure in esophageal cancer detecting and treating tumor cells earlier. In patients with locally advanced squamous cell carcinoma of the esophagus (ESCC), we profiled the gene expression of ESCC compared to corresponding normal biopsies for diagnostic markers by genome microarrays. Profiling of gene expression identified 4844 genes differentially expressed, 2122 upregulated and 2722 downregulated in ESCC. Twenty-three overexpressed candidates with best scores from significance analysis have been selected for further analysis by TaqMan low-density array-technique using a validation cohort of 40 patients. The verification rate was 100 % for ESCC. Twenty-two markers were additionally overexpressed in adenocarcinoma of the esophagus (EAC). The markers significantly overexpressed already in earlier tumor stages (pT1-2) of both histological subtypes (n = 19) have been clustered in a “diagnostic signature”: PLA2G7, PRAME, MMP1, MMP3, MMP12, LIlRB2, TREM2, CHST2, IGFBP2, IGFBP7, KCNJ8, EMILIN2, CTHRC1, EMR2, WDR72, LPCAT1, COL4A2, CCL4, and SNX10. The marker signature will be translated to clinical practice to prove its diagnostic impact. This diagnostic signature may contribute to the earlier detection of tumor cells, with the aim to complement clinical techniques resulting in the development of better detection of concepts of esophageal cancer for earlier therapy and more favorite prognosis.

Keywords

Esophageal cancer Diagnostic marker DNA microarrays Gene expression profiling 

Abbreviations

BIRC5

Baculoviral IAP (inhibitor of apoptosis protein) Repeat-containing 5

CCL4

Chemokine (C-C motif) ligand 4-like

CXCL6

Chemokine (C-X-C motif) ligand 6

CHST2

Carbohydrate (N-acetyl-glucosamine-6-O) sulfotransferase 2

Ct

Cycle threshold

CTHRC1

Collagen triple helix repeat containing 1

COL4A2

Collagen type IV, alpha2

EAC

Esophageal adenocarcinoma

ELISA

Enzyme-linked immunosorbent assay

EMILIN2

EGF-like module containing

EMR2

Elastin microfibril interfacer 2

ESCC

Esophageal squamous cell carcinoma

FDR

False discovery rate

IGFBP2

Insulin-like growth factor-binding protein 2

IGFBP7

Insulin-like growth factor-binding protein 7

KCNJ8

Potassium inwardly-rectifying channel subfamilyJ,member 8

KRT17

Keratin17

IGFBP2

Insulin-like growth factor-binding protein 2

LDA

Low density array

LIlRB2

Leucocyte immunoglobuline like receptor subfamily B, member2

LILRA3

Leucocyte immunoglobulin-like receptor subfamiliy A member 3

LILRB4

Leucocyte immunoglobuline-like receptor subfamily B, member4

LPCAT1

Lysophatidylcholineacyltrans-ferase 1

miR

MicroRNA

MMP1

Metalloproteinase 1

MMP3

Metalloproteinase 3

MMP12

Metalloproteinase 12

PLA2G7

Phospholipase A2 group VII

PRAME

Preferentially expressed antigen in melanoma

pT

Pathologic tumor stage

Rq

Relative quantity

RT

Reverse transcription

RT-PCR

Real-time polymerase chain reaction

SAM

Significance analysis of microarrays

SNX10

Sorting nexin 10

T

Tumor stage

TNM

Tumor-node-metastasis classification system of malignant tumors

TREM2

Triggering receptor expressed on myeloid cells 2

WDR72

WD repeat domain 72

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Laboratory for Molecular Oncology, General, Visceral and Cancer SurgeryUniversity Hospital of Cologne (CIO)CologneGermany
  2. 2.Caritasklinikum SaarbrückenSaarbrückenGermany
  3. 3.General, Visceral and Cancer SurgeryUniversity Hospital of Cologne (CIO)CologneGermany
  4. 4.Institute for PathologyUniversity Hospital of Cologne, Center for Integrated Oncology (CIO)CologneGermany