Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?
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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.
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.
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.
KeywordsColon cancer Liver metastasis Predictive biomarkers Prognostic factors
Beta 2 microglobulin
Bcl-2 associated X protein
v-Raf murine sarcoma viral oncogene homolog B1
- CCR 6
Chemokine receptor 6
Chemokine receptor 4
Cell adhesion promoter
Epidermal growth factor receptor
Excision repair cross-complementing factor 1
TNF factor superfamily member 6
Formalin fixed paraffin embedded
Chemotherapy scheme including 5-FU leucovorin and irinotecan
Chemotherapy scheme including 5-FU leucovorin and oxaliplatin
Glyceraldehyde 3-phosphate dehydrogenase reference gene
- GST Pi
Glutathione S-Transferase Pi
- h TERT
Human telomerase reverse transcriptase
v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog
Metastatic colorectal cancer
Matrix metalloproteinase 9
Phosphorylated v-akt murine thymoma viral oncogene homolog 1
Polymerase chain reaction
Phosphoinositide-3-Kinase, catalytic, alpha polypeptide
Phosphatase and tensin homolog
quantitative Polymerase chain reaction
Taq low density arrays
- TOP 1
- VEGF A
Vascular endothelial growth factor
Conflict of interest
All listed authors have no conflicts of interest regarding the material presented in this article.
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