Open Access Research article

Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma

Elana J Fertig1*, Qing Ren2, Haixia Cheng1, Hiromitsu Hatakeyama3, Adam P Dicker24, Ulrich Rodeck25, Michael Considine1, Michael F Ochs16 and Christine H Chung1

Author Affiliations

1 Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

2 Department of Radiation Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA

3 Department of Otolaryngology, Hokkaido University, Sapporo, Hokkaido, Japan

4 Department of Pharmacology and Experimental Therapeutics, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA

5 Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, USA

6 Department of Health Science Informatics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

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BMC Genomics 2012, 13:160  doi:10.1186/1471-2164-13-160

Published: 1 May 2012

Additional files

Additional file 3 :

Figure S3. Clustering of HaCaT expression data after fRMA colored by date (a). Analogous clustering after batch correction in (b).

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Additional file 7 :

File S1. CompleteAnalysis.R: R script used for to generate all analyses and figures.

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Additional file 8 :

File S2. TF2Gene_2010.R: R script encoding a list of transcription factor targets in TRANSFAC from ASAP.

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Additional file 9 :

File S3. PathwayHeatmap.R: Support script used to generate pathway-level heatmaps in Figures S1 and S3.

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Additional file 10 :

File S4. ExperimentalDescription.txt: Detailed annotation of experimental conditions summarized in Table 1.

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Additional file 11 :

File S5. SCC11CC8Annot.txt: Detailed annotation of the experimental conditions in the UMSCC1 and 1CC8 cell line expression datasets.

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Additional file 1 :

Figure S1.Box plot of six gene expression patterns inferred from the HaCaT gene expression data for each of the three CoGAPS simulations (pages 1–3) for the samples in Table 1. Plotted values are normalized to sum to one across all samples. All results for HaCaT-EGFRWT are colored in green, HaCaT-HRASVal12D in red, HaCaT-EGFRWT in grey, HaCaT-p65WT in blue, and HaCaT-vector in black. The y-axis is labeled according to the row of the inferred P matrix plotted in each panel. Specifically, (a) contains the pattern attributed to the baseline HaCaT activity, (b) attributed to HaCaT-HRASVal12D, (c) HaCaT-vector, (d) HaCaT-EGFRWT, (e) serum, and (f) HaCaT-p65WT.

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Additional file 2 :

Figure S2.Gene set statistics of the HaCaT expression data calculated from eq. 3 for each of the three CoGAPS simulations from blue for significantly downregulated to yellow for significantly upregulated according to the color bar. Columns are labeled according to the dominant experimental condition to which inferred CoGAPS patterns correspond and colored as indicated in the column color legend (red for the first CoGAPS simulation, green the second, and blue the third). The top set of statistics represents the gene set statistics computed at a pathway level. Colors along rows indicate the pathway for which activation statistics are calculated as indicated in the row color legend. The lower set of statistics represents the gene set statistics computed for the transcription factors activated by the pathway also indicated by colors in the rows associated with the pathway to which the transcription factor was assigned and indicated by the color code on the left.

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Additional file 4 :

Figure S4. χ2 fit from CoGAPS as a function of the number of patterns used in the matrix factorization for eq. 1.

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Additional file 6 :

Table S1. PathwayTableS1.txt: List of targets of transcription factors annotated to each pathway for pathway-level and transcription factor-level gene set analyses.

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Additional file 5 :

Figure S5. Heatmap comparing patterns inferred in CoGAPS as plotted Figure S2 (filled boxes on rows) to patterns that would be inferred from projecting expression patterns as described in the methods (open boxes on rows) colored according to the row figure legend. As indicated in the row figure legend, patterns are plotted for each of three CoGAPS simulations, colored in red (simulation 1), green (simulation 2), and blue (simulation 3) along the rows. The bars across the columns indicate media and forced expression conditions, colored according to the figure legend. Shading of these bars indicates media (white for serum starved, grey for serum, green for EGF, and blue for TNFα) while borders indicate forced expression (grey for HaCaTWT, black for HaCaT-vector, green for HaCaT-EGFRWT, blue for HaCaT-p65WT, and red for HaCaT-HRASVal12D).

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