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Gene Name ARHGDIB (Rho GDP Dissociation Inhibitor (GDI) β B3GNT1 (UDPGlcNAc:βGal β-1,3-Nacetylglucosaminyltransferase 1) B4GALT1 (UDPGal:βGlcNAc β 1,4galactosyltransferase, polypeptide 1) CTNNB1 (catenin, beta 1) CUX1 (cut-like homeobox 1) EIF3A (eukaryotic translation initiation factor 3, subunit A) FADD (Fas associated via death domain) FSCN1 (fascin actinbundling protein 1) HEXA (hexosaminidase A) PCBP2 (poly(rC) binding protein 2) PDIA3 (protein disulfide isomerase family A, member 3) POLR2A (polymerase II polypeptide A) S100A4 (S100 calcium binding protein A4) SDC1 (syndecan 1) SRSF2 (serine/argininerich splicing factor 2) STIP1 (stress-induced phosphoprotein 1) TCEB1 (transcription elongation factor B) TGF 1 (transforming growth factor, beta 1) Effects on Tumor Ref. Both Log2 Fold Change O vs M O vs Y O vs A M vs Y M vs A Y vs A (1, 2) -0.6541 -0.4321 -0.5128 0.2220 0.1414 -0.0807 Inhibits (3) 0.6048 -0.1637 -0.2436 -0.0799 Promotes (4) -0.3074 -0.4193 -0.4038 -0.1119 -0.0964 0.0155 Promotes (5) -0.5703 -0.8412 -0.3220 -0.2709 0.2483 0.5192 Inhibits (6) -0.5483 -0.5855 -0.3024 -0.0371 0.2459 0.2831 Promotes (7) -0.6112 -0.6778 -0.4621 -0.0666 0.1491 0.2157 Promotes (8) 0.4312 0.3442 0.1014 -0.0870 -0.1884 Promotes (9) -1.4195 -1.0807 -0.3833 0.3388 1.0362 0.6974 Promotes (10, 11) -0.7743 -0.5425 -0.2717 0.2318 0.5026 0.2708 Inhibits (12) -0.7270 -0.6081 -0.3711 0.1189 0.3559 0.2370 Promotes (13) -1.4168 -0.9836 -0.3972 0.4332 1.0197 0.5865 Promotes (14) -0.6701 -0.5241 -0.3379 0.1460 0.3322 0.1862 Promotes (15) -0.5497 -0.9786 -0.2846 -0.4289 0.2652 0.6941 Promotes (16) -0.6220 -0.4994 -0.4557 0.1664 0.0437 Promotes (17) -0.3823 -0.8971 -0.6749 -0.5148 -0.2926 0.2222 Promotes (18) -0.5598 -0.6239 -0.6151 -0.0641 -0.0553 0.0088 Promotes (19) 0.3450 0.1935 -0.0467 -0.2402 Promotes (20) -0.5532 -0.7938 -0.4962 -0.2406 0.0570 0.2976 0.4411 0.5326 0.5386 0.3612 0.2984 0.1226 Supplemental Table 4. Eighteen key genes involved in age-dependent tumor progression. These 18 genes were determined by finding the common genes for old tumor samples (O) versus all other ages (Adolescent (A), Young Adult (YA), and Middle-Aged (MA)) that are in common between the significant upstream regulators and the biofunction analysis. The second and third columns denote the effects these genes have on tumor progression based on the literature. The genes in bold and italic are found to overlap with genes found in the Gene Set Enrichment Analysis (GSEA) gene sets for old tumor samples vs other aged tumor samples. 1. Li X, Wang J, Zhang X, Zeng Y, Liang L, Ding Y. Overexpression of RhoGDI2 correlates with tumor progression and poor prognosis in colorectal carcinoma. Ann Surg Oncol. 2012;19:145-53. 2. Said N, Sanchez-Carbayo M, Smith SC, Theodorescu D. RhoGDI2 suppresses lung metastasis in mice by reducing tumor versican expression and macrophage infiltration. J Clin Invest. 2012;122:1503-18. 3. Lee SH, Hatakeyama S, Yu SY, Bao X, Ohyama C, Khoo KH, et al. Core3 O-glycan synthase suppresses tumor formation and metastasis of prostate carcinoma PC3 and LNCaP cells through down-regulation of alpha2beta1 integrin complex. J Biol Chem. 2009;284:1715769. 4. Choi HJ, Chung TW, Kim CH, Jeong HS, Joo M, Youn B, et al. Estrogen induced beta- 1,4-galactosyltransferase 1 expression regulates proliferation of human breast cancer MCF-7 cells. Biochem Biophys Res Commun. 2012;426:620-5. 5. King TJ, Gurley KE, Prunty J, Shin JL, Kemp CJ, Lampe PD. Deficiency in the gap junction protein connexin32 alters p27Kip1 tumor suppression and MAPK activation in a tissuespecific manner. Oncogene. 2005;24:1718-26. 6. McNerney ME, Brown CD, Wang X, Bartom ET, Karmakar S, Bandlamudi C, et al. CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia. Blood. 2012. 7. Saletta F, Suryo Rahmanto Y, Richardson DR. The translational regulator eIF3a: the tricky eIF3 subunit! Biochim Biophys Acta. 2010;1806:275-86. 8. Tourneur L, Buzyn A, Chiocchia G. FADD adaptor in cancer. Med Immunol. 2005;4:1. 9. Al-Alwan M, Olabi S, Ghebeh H, Barhoush E, Tulbah A, Al-Tweigeri T, et al. Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. PLoS One. 2011;6:e27339. 10. Pasztoi M, Nagy G, Geher P, Lakatos T, Toth K, Wellinger K, et al. Gene expression and activity of cartilage degrading glycosidases in human rheumatoid arthritis and osteoarthritis synovial fibroblasts. Arthritis Res Ther. 2009;11:R68. 11. Jiang SS, Chen CH, Tseng KY, Tsai FY, Wang MJ, Chang IS, et al. Gene expression profiling suggests a pathological role of human bone marrow-derived mesenchymal stem cells in aging-related skeletal diseases. Aging (Albany NY). 2011;3:672-84. 12. Roychoudhury P, Paul RR, Chowdhury R, Chaudhuri K. HnRNP E2 is downregulated in human oral cancer cells and the overexpression of hnRNP E2 induces apoptosis. Mol Carcinog. 2007;46:198-207. 13. Pressinotti NC, Klocker H, Schafer G, Luu VD, Ruschhaupt M, Kuner R, et al. Differential expression of apoptotic genes PDIA3 and MAP3K5 distinguishes between low- and high-risk prostate cancer. Mol Cancer. 2009;8:130. 14. Saviozzi S, Cordero F, Lo Iacono M, Novello S, Scagliotti GV, Calogero RA. Selection of suitable reference genes for accurate normalization of gene expression profile studies in nonsmall cell lung cancer. BMC Cancer. 2006;6:200. 15. Yan XL, Jia YL, Chen L, Zeng Q, Zhou JN, Fu CJ, et al. Hepatocellular carcinoma- associated mesenchymal stem cells promote hepatocarcinoma progression: Role of the S100A4-miR155-SOCS1-MMP9 axis. Hepatology. 2013. 16. Goodison S, Chang M, Dai Y, Urquidi V, Rosser CJ. A multi-analyte assay for the non- invasive detection of bladder cancer. PLoS One. 2012;7:e47469. 17. Edmond V, Brambilla C, Brambilla E, Gazzeri S, Eymin B. SRSF2 is required for sodium butyrate-mediated p21WAF1 induction and premature senescence in human lung carcinoma cell lines. Cell Cycle. 2011;10:1968-77. 18. Wang TH, Chao A, Tsai CL, Chang CL, Chen SH, Lee YS, et al. Stress-induced phosphoprotein 1 as a secreted biomarker for human ovarian cancer promotes cancer cell proliferation. Mol Cell Proteomics. 2010;9:1873-84. 19. Jalava SE, Porkka KP, Rauhala HE, Isotalo J, Tammela TL, Visakorpi T. TCEB1 promotes invasion of prostate cancer cells. Int J Cancer. 2009;124:95-102. 20. Nguyen DH, Martinez-Ruiz H, Barcellos-Hoff MH. Consequences of epithelial or stromal TGFbeta1 depletion in the mammary gland. J Mammary Gland Biol Neoplasia. 2011;16:147-55.