The survivin -31 snp in human colorectal cancer correlates with survivin splice variant expression and improved overall survival.
BACKGROUND
survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue. Moreover, the 9386C/T and -31G/C polymorphisms were investigated.


METHODS
quantitative RT-PCR was used to assess mRNA levels in fresh/frozen tissue samples. Protein levels were immunohistochemically evaluated on formalin-fixed paraffin-embedded tissue sections. Individuals were genotyped using real time PCR.


RESULTS
expression of all 5 survivin splice variants as well as survivin protein was elevated in colorectal carcinomas compared to normal tissue. Specific splice variant expression differentially correlated with clinicopathological parameters. Furthermore, both snps correlated with splice variant levels or their ratios in colorectal carcinomas while the -31G/C snp may be related to CRC development and improved overall survival.


CONCLUSIONS
our results support a role of survivin in colorectal carcinogenesis while the -31G/C snp may constitute a marker of survival.
Antonacopoulou
Anna G
AG
Molecular Oncology Laboratory, Medical School, University of Patras, Rion, Greece.
Floratou
Konstantina
K
Bravou
Vasiliki
V
Kottorou
Anastasia
A
Dimitrakopoulos
Fotinos-Ioannis
FI
Marousi
Stella
S
Stavropoulos
Michalis
M
Koutras
Agelos K
AK
Scopa
Chrisoula D
CD
Kalofonos
Haralabos P
HP
D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis* / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D000077022:Survivin