Skp2 gene copy number aberrations are common in non-small cell lung carcinoma, and its overexpression in tumors with ras mutation is a poor prognostic marker.
OBJECTIVE
Skp2 plays a critical role in cell cycle progression, especially at the G(1)-S transition, putatively through its control of several cell cycle regulator proteins. The Skp2 gene is located on a region of chromosome 5p that is commonly overrepresented in lung cancer. The present study aimed to evaluate Skp2 abnormalities and their prognostic value in non-small cell lung cancer (NSCLC).


METHODS
In total 16 NSCLC cell lines and 163 primary tumors were included in studies to measure Skp2 relative gene copy number, mRNA abundance, and protein level. The tumors were also evaluated for p27 protein expression level and ras mutation. These values were correlated with the clinical and pathological features of the patients.


RESULTS
Skp2 relative gene copy number aberrations were found in 88 and 65% of NSCLC cell lines and primary tumors, respectively. Overrepresentation was especially common among squamous cell carcinoma (74%). Both gene copy overrepresentation (13%) and loss (35%) were found in adenocarcinoma. Skp2 relative gene copy number was significantly correlated with mRNA and protein levels, but none of these were correlated with p27 protein levels. Neither high Skp2 protein expression nor ras mutation was prognostically significant. In NSCLCs with ras mutation, however, high Skp2 protein expression was a significant independent poor prognostic marker.


CONCLUSIONS
There appears to be a synergistic interaction between high Skp2 protein expression and ras mutation with negative impact on the survival of NSCLC patients.
Zhu
Chang Qi
CQ
University Health Network, Ontario Cancer Institute and Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.
Blackhall
Fiona H
FH
Pintilie
Melania
M
Iyengar
Pratibha
P
Liu
Ni
N
Ho
James
J
Chomiak
Taylor
T
Lau
Davina
D
Winton
Timothy
T
Shepherd
Frances A
FA
Tsao
Ming-Sound
MS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics*; D016019:Survival Analysis
D017931:DNA Primers; D044786:S-Phase Kinase-Associated Proteins