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Supplementary Data Supplementary data Supplementary figure 1. Heatmap of common response, 2 and 6 hours after irradiation. Heatmap of the common response to 4 Gy irradiation in all 32 cell lines, adapted from the BRB-array tools time course plug-in output. Supplementary table 1 gives an overview of cell line characteristics. Supplementary table 2 describes the patient characteristics for the 34 patients in the validation cohort. Supplementary table 3 describes the references used for the definition of miR functions stated in table 1. Supplementary table 4 lists 1226 genes significantly correlated with radioresistance from a BRB time course plug-in analysis. Supplementary table 5 lists the genes in our p53 and DNA repair signatures. Supplementary table 6 lists the HNSCC EMT-scores for the 32 cell lines. Supplementary table 7 lists the 1189 genes in the HNSCC-EMT signature. Supplementary table 8 shows results of testing gene sets for reactive oxygen species, DNA repair, cell cycle phase and several means of cell death against the EMT gene set. Supplementary figure 1. Heatmap of common response, 2 and 6 hours after irradiation. Heatmap of the common response to 4 Gy irradiation in all 32 cell lines, adapted from the BRB-array tools time course plug-in output. Supplementary table 1. Overview of cell line characteristics for the 32 cell lines. Cell line Radiosens- Passage Patient Primary Location T N M Type of Grade Previous itivity (AUC) tested sex Specimen Treatment UT-SCC-1A 1.7 19 F gingiva 2 1 0 rT 2 RT mandibulae UT-SCC-2 1.8 12 M floor of mouth 4 1 0 pT 2 no UT-SCC-4 1.7 9 F supraglottic 3 0 0 rN 2 RT UT-SCC-5 2.3 14 M tongue 1 1 0 ppT 2 RT UT-SCC-6A 2.6 27 F supraglottic 2 1 0 rT 1 RT UT-SCC-7 2 12 M cutis regio 1 0 0 rN 2 RT temporalis UT-SCC-8 1.9 27 M supraglottic 2 0 0 pT 1 no UT-SCC-9 1.4 13 M glottic larynx 2 1 0 N 1 RT UT-SCC-12 2.1 14 F cutis nasi 2 0 0 pT 1 no UT-SCC-15 2.1 15 M tongue 1 0 0 rT 1 RT UT-SCC-16A 1.8 17 F tongue 3 0 0 pT 3 RT UT-SCC-19A 1.7 14 M glottic larynx 4 0 0 pT 2 no UT-SCC-19B 1.7 14 M glottic larynx 4 0 0 ppT 2 RT UT-SCC-20A 2.1 19 F floor of mouth 1 0 0 pT 2 RT UT-SCC-22 1.8 25 M glottic larynx 1 0 0 rT 2 RT UT-SCC-23 1.6 22 M glottic larynx 3 0 0 ppT 1 RT UT-SCC-24A 2.6 24 M tongue 2 0 0 pT 2 no UT-SCC-25 2.2 12 M tongue 2 0 0 pT 1 RT UT-SCC-27 1.9 12 M gingiva 2 0 0 rT 3 RT mandibulae UT-SCC-32 1.7 16 M tongue 3 0 0 ppT 1 RT UT-SCC-36 2.2 8 M floor of mouth 4 1 0 pT 3 no UT-SCC-42A 2.1 7 M supraglottic 4 3 0 pT 3 no UT-SCC-45 2 17 M floor of mouth 3 1 0 pT 3 no UT-SCC-46A 1.6 11 M gingiva maxillae 1 0 0 pT 3 no UT-SCC-47 2 13 M floor of mouth 2 0 0 pT 3 no UT-SCC-48 1.6 15 M parotid gland 3 0 0 pT 2 no UT-SCC-54C 2.3 14 F buccal mucosa 0 0 0 rN 0 RT UT-SCC-60B 2.2 13 M tonsil 4 1 0 ppN 1 RT UT-SCC-76A 2.5 13 M tongue 3 0 0 pT 2 no UT-SCC-77 2.5 23 M tongue 1 0 0 rN 2 no UT-SCC-79A 2.4 14 F parotid gland 2 0 0 rT 2 no UT-SCC-90 2.2 20 M tongue 1 0 0 rT 2 RT Supplementary table 1: Overview of the properties of all 32 cell lines. p= primary tumor, r= recurrent tumor, pp = persistent primary tumor, T=from the primary tumor location, N = from the lymph node. Supplementary table 2: patient characteristics for the 34 patients in the validation cohort. Cures Recurrences N 17 17 Sex Male 59% 59% Female 41% 41% Age (years) Average 68 67 Treatment year Average 2007 2007 T-stage T2 65% 59% T3 35% 41% Subsite Glottic 47% 47% Supraglottic 53% 53% Follow up Average 3.9 3.7 (years) Supplementary table 3: references for the miR functions, as stated in table 1. miR miR function miR-203a Inhibit growth, self-renewal, migration, invasion and EMT (1–4) miR-205-5p Promote apoptosis, inhibit growth, migration, invasion and EMT (5–8) miR-452-5p Reduce stem-like traits and tumorigenesis, EMT (9,10) miR-200b-3p Reduced proliferation, migration, invasion and EMT (5,11–16) miR-429 Inhibit proliferation and EMT (5,15,17,18) miR-141-3p Inhibit EMT (5,19) miR-200a-3p Inhibit EMT (5,15,16) miR-7-5p Inhibit invasion, self renewal and EMT (20,21). Promote apoptosis (22) miR-138-5p Inhibit proliferation, invasion, migration, modify DNA damage response (23,24) miR-34a-5p Inhibit proliferation, invasion, metastasis, stemness, EMT (25,26) miR-142-3p Maintenance of dendritic cells (27) Inhibit growth and stemness (28) miR-33b-5p Reduce proliferation, induce G1 arrest (29), cholesterol transport (30) miR-130a-3p enhances cell proliferation and migration (31), reduce trail resistance and migration (32) miR-193b-3p Proliferation, differentiation, apoptosis (33) miR-151a-5p Increased migration, invasion (34–36), also inhibition of EMT (37) miR-10a-5p Apoptosis (33) miR-424-5p Increased proliferation, migration and invasion, inhibit apoptosis (38,39) miR-15a-5p Sensitize cells to apoptosis (40,41) 1. Chen J, Tran UM, Rajarajacholan U, Thalappilly S, Riabowol K. ING1b-inducible microRNA203 inhibits cell proliferation. British journal of cancer. Nature Publishing Group; 2013;108:1143–8. 2. Abella V, Valladares M, Rodriguez T, Haz M, Blanco M, Tarrío N, et al. miR-203 regulates cell proliferation through its influence on Hakai expression. PloS one. 2012;7:e52568. 3. Moes M, Le Béchec A, Crespo I, Laurini C, Halavatyi A, Vetter G, et al. A novel network integrating a miRNA- 203/SNAI1 feedback loop which regulates epithelial to mesenchymal transition. PloS one. 2012;7:e35440. 4. Zhang Z, Zhang B, Li W, Fu L, Fu L, Zhu Z, et al. Epigenetic Silencing of miR-203 Upregulates SNAI2 and Contributes to the Invasiveness of Malignant Breast Cancer Cells. Genes & cancer. 2011;2:782–91. 5. Gregory P a, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature cell biology. 2008;10:593–601. 6. Lee J-Y, Park MK, Park J-H, Lee HJ, Shin DH, Kang Y, et al. Loss of the polycomb protein Mel-18 enhances the epithelial-mesenchymal transition by ZEB1 and ZEB2 expression through the downregulation of miR-205 in breast cancer. Oncogene. 2013; 7. Xie H, Zhao Y, Caramuta S, Larsson C, Lui W-O. miR-205 expression promotes cell proliferation and migration of human cervical cancer cells. PloS one. 2012;7:e46990. 8. Majid S, Saini S, Dar AA, Hirata H, Shahryari V, Tanaka Y, et al. MicroRNA-205 inhibits Src-mediated oncogenic pathways in renal cancer. Cancer research. 2011;71:2611–21. 9. Liu L, Chen K, Wu J, Shi L, Hu B, Cheng S, et al. Downregulation of miR-452 Promotes Stem-Like Traits and Tumorigenicity of Gliomas. Clinical cancer research. 2013;3429–38. 10. Sheehy NT, Cordes KR, White MP, Ivey KN, Srivastava D. The neural crest-enriched microRNA miR-452 regulates epithelial-mesenchymal signaling in the first pharyngeal arch. Development. 2010;137:4307–16. 11. Li A, Omura N, Hong S-M, Vincent A, Walter K, Griffith M, et al. Pancreatic cancers epigenetically silence SIP1 and hypomethylate and overexpress miR-200a/200b in association with elevated circulating miR-200a and miR-200b levels. Cancer research. 2010;70:5226–37. 12. Sun L, Yao Y, Liu B, Lin Z, Lin L, Yang M, et al. MiR-200b and miR-15b regulate chemotherapy-induced epithelial- mesenchymal transition in human tongue cancer cells by targeting BMI1. Oncogene. 2012;31:432–45. 13. Kurashige J, Kamohara H, Watanabe M, Hiyoshi Y, Iwatsuki M, Tanaka Y, et al. MicroRNA-200b regulates cell proliferation, invasion, and migration by directly targeting ZEB2 in gastric carcinoma. Annals of surgical oncology. 2012;19 Suppl 3:S656–64. 14. Chen Y, Xiao Y, Ge W, Zhou K, Wen J, Yan W, et al. miR-200b inhibits TGF-β1-induced epithelial-mesenchymal transition and promotes growth of intestinal epithelial cells. Cell death & disease. 2013;4:e541. 15. Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, et al. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer research. 2008;68:7846–54. 16. Enkhbaatar Z, Terashima M, Oktyabri D, Tange S, Ishimura A, Yano S, et al. KDM5B histone demethylase controls epithelial-mesenchymal transition of cancer cells by regulating the expression of the microRNA-200 family. Cell cycle. 2013;12. 17. Chen J, Wang L, Matyunina L V, Hill CG, McDonald JF.
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