Significant overexpression of Hsp110 gene during colorectal cancer progression.
Colorectal cancer (CRC) is one of the most frequent malignant diseases in the world. Metastatic spread of the cancer to the lymph nodes is a crucial factor for progression and therapeutic management of the disease. We analysed gene expression profiles of CRC patiens by low-density cancer-focused oligonucleotide microarrays to identify new predictive markers of the extent of the disease and for better understanding of CRC progression. Relative expression levels of 440 genes known to be involved in cancer biology were obtained by low-density oligonucleotide microarrays from 20 tumor samples. Statistical analysis of gene expression data identified 3 genes (HSP110, HYOU1 and TCTP) significantly up-regulated in primary tumors of patients who developed lymph node metastasis. We have shown, for the first time, that up-regulation HSP110 and HYOU1 expression is associated with lymph node involvement in CRC. We validated the differences in HSP110 expression in an independent group of 30 patients of all clinical stages by real-time PCR. We identified significant up-regulation of HSP110 expression in colorectal tumors compared to adjacent non-tumoral tissue (p<0.0003). We observed significant differences of HSP110 gene expression between metastatic and localized disease (p=0.031) and negative trend of HSP110 gene expression and overall survival of CRC patients. We suggest that HSP110 gene is a promising molecular predictor in CRC.
Slaby
O
O
Masaryk Memorial Cancer Institute, Department of Oncological and Experimental Pathology, 656 53 Brno, Czech Republic. slaby@mou.cz
Sobkova
K
K
Svoboda
M
M
Garajova
I
I
Fabian
P
P
Hrstka
R
R
Nenutil
R
R
Sachlova
M
M
Kocakova
I
I
Michalek
J
J
Smerdova
T
T
Knoflickova
D
D
Vyzula
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D050957:HSP110 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000090324:Tumor Protein, Translationally-Controlled 1; D015854:Up-Regulation
D050957:HSP110 Heat-Shock Proteins; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1