TY - JOUR
T1 - Increased SOX2 gene copy number is associated with FGFR1 and PIK3CA gene gain in non-small cell lung cancer and predicts improved survival in early stage disease
AU - Toschi, Luca
AU - Finocchiaro, Giovanna
AU - Nguyen, Teresa T.
AU - Skokan, Margaret C.
AU - Giordano, Laura
AU - Gianoncelli, Letizia
AU - Perrino, Matteo
AU - Siracusano, Licia
AU - Di Tommaso, Luca
AU - Infante, Maurizio
AU - Alloisio, Marco
AU - Roncalli, Massimo
AU - Scorsetti, Marta
AU - Jänne, Pasi A.
AU - Santoro, Armando
AU - Varella-Garcia, Marileila
PY - 2014/4/1
Y1 - 2014/4/1
N2 - Background: We aimed to investigate prevalence and prognostic role of SOX2, PIK3CA, FGFR1 and BRF2 gene gain in patients with surgically resected non-small cell lung cancer (NSCLC). Methods: SOX2, PIK3CA, FGFR1 and BRF2 gene copy number was assessed by fluorescence in situ hybridization (FISH) in arrayed tissue cores from 447 resected NSCLCs. Results: Increased gene copy number (FISH+) for SOX2, PIK3CA, FGFR1 and BRF2 was observed in 23.6%, 29.2%, 16.6% and 14.9% of cases, respectively. FISH+ status for each gene was significantly associated with smoking history, squamous cell carcinoma (SCC) histology, and increased copy number of the other studied genes. Multivariate analysis of overall survival indicated increased SOX2 gene copy number (P = 0.008), stage I-II (P<0.001), and adenocarcinoma or SCC histology (P = 0.016) as independent, favorable prognostic factors. A statistically significant interaction was observed between stage and SOX2 gene status (P = 0.021), indicating that the prognostic impact of SOX2 gene gain differs across stages and is limited to patients with stage I-II disease (HR 0.44, 95% CI: 0.25-0.77; P = 0.004, adjusted for histology). Conclusions: Increased SOX2 gene copy number is an independent and favorable prognostic factor in surgically resected, early stage NSCLC, regardless of histology. SOX2, PIK3CA, FGFR1 and BRF2 gene gains are likely to occur concurrently, with potentially relevant implications for the development of new therapeutic strategies.
AB - Background: We aimed to investigate prevalence and prognostic role of SOX2, PIK3CA, FGFR1 and BRF2 gene gain in patients with surgically resected non-small cell lung cancer (NSCLC). Methods: SOX2, PIK3CA, FGFR1 and BRF2 gene copy number was assessed by fluorescence in situ hybridization (FISH) in arrayed tissue cores from 447 resected NSCLCs. Results: Increased gene copy number (FISH+) for SOX2, PIK3CA, FGFR1 and BRF2 was observed in 23.6%, 29.2%, 16.6% and 14.9% of cases, respectively. FISH+ status for each gene was significantly associated with smoking history, squamous cell carcinoma (SCC) histology, and increased copy number of the other studied genes. Multivariate analysis of overall survival indicated increased SOX2 gene copy number (P = 0.008), stage I-II (P<0.001), and adenocarcinoma or SCC histology (P = 0.016) as independent, favorable prognostic factors. A statistically significant interaction was observed between stage and SOX2 gene status (P = 0.021), indicating that the prognostic impact of SOX2 gene gain differs across stages and is limited to patients with stage I-II disease (HR 0.44, 95% CI: 0.25-0.77; P = 0.004, adjusted for histology). Conclusions: Increased SOX2 gene copy number is an independent and favorable prognostic factor in surgically resected, early stage NSCLC, regardless of histology. SOX2, PIK3CA, FGFR1 and BRF2 gene gains are likely to occur concurrently, with potentially relevant implications for the development of new therapeutic strategies.
UR - http://www.scopus.com/inward/record.url?scp=85000415133&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85000415133&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0095303
DO - 10.1371/journal.pone.0095303
M3 - Article
VL - 9
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 4
M1 - e0095303
ER -