title: Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?
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.
  
  
  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.
authors.affiliation: Medical Oncology Department, Infanta Sofía University Hospital, Paseo de Europa 34, San Sebastián de los Reyes, 28702, Madrid, Spain, miriam.lopez@telefonica.net.
authors.forename: M
authors.initials: M
authors.lastname: López-Gómez
authors.forename: J
authors.initials: J
authors.lastname: Moreno-Rubio
authors.forename: I
authors.initials: I
authors.lastname: Suárez-García
authors.forename: P
authors.initials: P
authors.lastname: Cejas
authors.forename: R
authors.initials: R
authors.lastname: Madero
authors.forename: E
authors.initials: E
authors.lastname: Casado
authors.forename: A M
authors.initials: AM
authors.lastname: Jiménez
authors.forename: M
authors.initials: M
authors.lastname: Sereno
authors.forename: C
authors.initials: C
authors.lastname: Gómez-Raposo
authors.forename: F
authors.initials: F
authors.lastname: Zambrana
authors.forename: M
authors.initials: M
authors.lastname: Merino
authors.forename: D
authors.initials: D
authors.lastname: Fernández-Luengas
authors.forename: J
authors.initials: J
authors.lastname: Feliu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D051901:Smad4 Protein / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C071447:ERCC1 protein, human; D004720:Endonucleases