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Clinical and Translational Oncology

, Volume 17, Issue 4, pp 322–329 | Cite as

Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?

  • M. López-GómezEmail author
  • J. Moreno-Rubio
  • I. Suárez-García
  • P. Cejas
  • R. Madero
  • E. Casado
  • A. M. Jiménez
  • M. Sereno
  • C. Gómez-Raposo
  • F. Zambrana
  • M. Merino
  • D. Fernández-Luengas
  • J. Feliu
Research Article

Abstract

Background

Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases.

Patients and methods

We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student’s t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson’s correlation coefficient.

Results

The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP (p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers.

Conclusions

We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy.

Keywords

Colon cancer Liver metastasis Predictive biomarkers Prognostic factors 

Abbreviations

5FU

5-Fluorouracil

B2M

Beta 2 microglobulin

BAX

Bcl-2 associated X protein

BRAF

v-Raf murine sarcoma viral oncogene homolog B1

CCR 6

Chemokine receptor 6

CXCR4

Chemokine receptor 4

DNA

Deoxyribonucleic acid

DPYD

Dihydropyrimidine dehydrogenase

E-cadherin

Cell adhesion promoter

EGFR

Epidermal growth factor receptor

ERCC1

Excision repair cross-complementing factor 1

FAS/CD95

TNF factor superfamily member 6

FFPE

Formalin fixed paraffin embedded

FOLFIRI

Chemotherapy scheme including 5-FU leucovorin and irinotecan

FOLFOX

Chemotherapy scheme including 5-FU leucovorin and oxaliplatin

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase reference gene

GST Pi

Glutathione S-Transferase Pi

h TERT

Human telomerase reverse transcriptase

IHC

Immunohistochemistry

KRAS

v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog

mCRC

Metastatic colorectal cancer

MMP-9

Matrix metalloproteinase 9

p

p value

pAKT

Phosphorylated v-akt murine thymoma viral oncogene homolog 1

PCR

Polymerase chain reaction

PIK3CA

Phosphoinositide-3-Kinase, catalytic, alpha polypeptide

PLAU

Urokinase-type plasminogen

PTEN

Phosphatase and tensin homolog

qPCR

quantitative Polymerase chain reaction

RNA

Ribonucleic Acid

TLDA

Taq low density arrays

TOP 1

Topoisomerase I

TYMP

Thymidine phosphorylase

TYMS

Thymidylate synthase

THBS1

Thrombospondin 1

VEGF A

Vascular endothelial growth factor

Notes

Conflict of interest

All listed authors have no conflicts of interest regarding the material presented in this article.

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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2014

Authors and Affiliations

  • M. López-Gómez
    • 1
    Email author
  • J. Moreno-Rubio
    • 7
  • I. Suárez-García
    • 3
  • P. Cejas
    • 2
  • R. Madero
    • 4
  • E. Casado
    • 1
  • A. M. Jiménez
    • 1
  • M. Sereno
    • 1
  • C. Gómez-Raposo
    • 1
  • F. Zambrana
    • 1
  • M. Merino
    • 1
  • D. Fernández-Luengas
    • 5
  • J. Feliu
    • 6
  1. 1.Medical Oncology DepartmentInfanta Sofía University HospitalMadridSpain
  2. 2.Translational Oncology DepartmentLa Paz University HospitalMadridSpain
  3. 3.Internal Medicine DepartmentInfanta Sofía University HospitalMadridSpain
  4. 4.Statistics DepartmentLa Paz University HospitalMadridSpain
  5. 5.General Surgery DepartmentInfanta Sofía University HospitalMadridSpain
  6. 6.Medical Oncology DepartmentLa Paz University HospitalMadridSpain
  7. 7.Precision Oncology Laboratory (POL)Infanta Sofía University HospitalMadridSpain

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