TY - JOUR
T1 - Analysis of gene expression profiles reveals novel correlations with the clinical course of colorectal cancer
AU - Cavalieri, Duccio
AU - Dolara, Piero
AU - Mini, Enrico
AU - Luceri, Cristina
AU - Castagnini, Cinzia
AU - Toti, Simona
AU - Maciag, Karolina
AU - De Filippo, Carlotta
AU - Nobili, Stefania
AU - Morganti, Maria
AU - Napoli, Cristina
AU - Tonini, Giulia
AU - Baccini, Michela
AU - Biggeri, Annibale
AU - Tonelli, Francesco
AU - Valanzano, Rosa
AU - Orlando, Claudio
AU - Gelmini, Stefania
AU - Cianchi, Fabio
AU - Messerini, Luca
AU - Luzzatto, Lucio
PY - 2007
Y1 - 2007
N2 - In order to discover potential markers of prognosis in colorectal cancer (CRC) we have determined gene expression profiles, using cDNA microarrays in CRC samples obtained from 19 patients in Dukes stages C and D, with favorable clinical course (Dukes C patients, survival >5 years after surgery, group A, n = 7) or unfavorable clinical course (Dukes stage C and D patients, survival <5 years after surgery, group B, n = 12). Gene expression was measured in RNA from each tumor, using a pool of equal amounts of RNA from all tumors as a reference. To identify and rank differentially expressed genes we used three different analytical methods: (i) Significance Analysis of Microarrays (SAM), (ii) Cox's Proportional Hazard Model, and (iii) Trend Filter (a mathematical method for the assessment of numerical trends). The level of expression of a gene in an individual tumor was regarded as of interest when that gene was identified as differentially expressed by at least two of these three methods. By these stringent criteria we identified eight genes (ITGB2, MRPS11, NPR1, TXNL2, PHF10, PRSS8, KCNK3, JAK3) that were correlated with prolonged survival after surgery. Pathway analysis showed that patients with favorable prognosis had several activated metabolic pathways (carbon metabolism, transcription, amino acid and nitrogen metabolism, signaling and fibroblast growth factor receptor pathways). To further validate individual gene expression findings, the RNA level of each gene identified as a marker with microarrays was measured by real-time RT-PCR in CRC samples from an independent group of 55 patients. In this set of patients the Cox Proportional Hazard Model analysis demonstrated a significant association between increased patient survival and low expression of ITGB2 (p = 0.011) and NPR1 (p = 0.023) genes.
AB - In order to discover potential markers of prognosis in colorectal cancer (CRC) we have determined gene expression profiles, using cDNA microarrays in CRC samples obtained from 19 patients in Dukes stages C and D, with favorable clinical course (Dukes C patients, survival >5 years after surgery, group A, n = 7) or unfavorable clinical course (Dukes stage C and D patients, survival <5 years after surgery, group B, n = 12). Gene expression was measured in RNA from each tumor, using a pool of equal amounts of RNA from all tumors as a reference. To identify and rank differentially expressed genes we used three different analytical methods: (i) Significance Analysis of Microarrays (SAM), (ii) Cox's Proportional Hazard Model, and (iii) Trend Filter (a mathematical method for the assessment of numerical trends). The level of expression of a gene in an individual tumor was regarded as of interest when that gene was identified as differentially expressed by at least two of these three methods. By these stringent criteria we identified eight genes (ITGB2, MRPS11, NPR1, TXNL2, PHF10, PRSS8, KCNK3, JAK3) that were correlated with prolonged survival after surgery. Pathway analysis showed that patients with favorable prognosis had several activated metabolic pathways (carbon metabolism, transcription, amino acid and nitrogen metabolism, signaling and fibroblast growth factor receptor pathways). To further validate individual gene expression findings, the RNA level of each gene identified as a marker with microarrays was measured by real-time RT-PCR in CRC samples from an independent group of 55 patients. In this set of patients the Cox Proportional Hazard Model analysis demonstrated a significant association between increased patient survival and low expression of ITGB2 (p = 0.011) and NPR1 (p = 0.023) genes.
KW - Colorectal cancer prognosis
KW - Gene expression
KW - Microarrays
KW - Real-time RT-PCR
UR - http://www.scopus.com/inward/record.url?scp=38949207223&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38949207223&partnerID=8YFLogxK
U2 - 10.3727/096504007783438376
DO - 10.3727/096504007783438376
M3 - Article
C2 - 18306933
AN - SCOPUS:38949207223
SN - 0965-0407
VL - 16
SP - 535
EP - 548
JO - Oncology Research
JF - Oncology Research
IS - 11
ER -