Supplementary Figures 1-5 - PDF file 342K, Figure S1. The IGV plot of copy number variation for 152 TCGA samples in 3q regions. The samples are in descending order according to the average expression scores. Figure S2. The effect of knockdown SENP2 expression on NSCLC cells. Figure S3. Three-gene expression-based 3q26-29 stratification informs response to adjuvant chemotherapy on different stage patients. Figure S4 Relationship between patient stratification based on expression value of each of three genes and response to adjuvant chemotherapy. Figure S5. Copy number alteration of SENP family members in TCGA lung SCC dataset (n=177)
ARTICLE ABSTRACT
Purpose: Chromosome 3q26-29 is a critical region of genomic amplification in lung squamous cell carcinomas (SCC). Identification of candidate drivers in this region could help uncover new mechanisms in the pathogenesis and potentially new targets in SCC of the lung.Experimental Design: We conducted a meta-analysis of seven independent datasets containing a total of 593 human primary SCC samples to identify consensus candidate drivers in 3q26-29 amplicon. Through integrating protein–protein interaction network information, we further filtered for candidates that may function together in a network. Computationally predicted candidates were validated using RNA interference (RNAi) knockdown and cell viability assays. Clinical relevance of the experimentally supported drivers was evaluated in an independent cohort of 52 lung SCC patients using survival analysis.Results: The meta-analysis identified 20 consensus candidates, among which four (SENP2, DCUN1D1, DVL3, and UBXN7) are involved in a small protein–protein interaction network. Knocking down any of the four proteins led to cell growth inhibition of the 3q26-29–amplified SCC. Moreover, knocking down of SENP2 resulted in the most significant cell growth inhibition and downregulation of DCUN1D1 and DVL3. Importantly, a gene expression signature composed of SENP2, DCUN1D1, and DVL3 stratified patients into subgroups with different response to adjuvant chemotherapy.Conclusion: Together, our findings show that SENP2, DCUN1D1, and DVL3 are candidate driver genes in the 3q26-29 amplicon of SCC, providing novel insights into the molecular mechanisms of disease progression and may have significant implication in the management of SCC of the lung. Clin Cancer Res; 19(20); 5580–90. ©2013 AACR.
