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Diagnostic marker signature for esophageal cancer from transcriptome analysis

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.

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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

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Acknowledgments

We acknowledge Michaela Heitmann, Susanne Neiß, and Anke Wienand-Dorweiler for their excellent technical assistance.

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Correspondence to Ute Warnecke-Eberz.

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Warnecke-Eberz, U., Metzger, R., Hölscher, A.H. et al. Diagnostic marker signature for esophageal cancer from transcriptome analysis. Tumor Biol. 37, 6349–6358 (2016). https://doi.org/10.1007/s13277-015-4400-4

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  • DOI: https://doi.org/10.1007/s13277-015-4400-4

Keywords

  • Esophageal cancer
  • Diagnostic marker
  • DNA microarrays
  • Gene expression profiling