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TABLE S1 Summary of high-confidence protein identifications in BCPAP, C643, and SW1736 thyroid cancer cell lines

TABLE S2 MS/MS spectra of the identified peptides

TABLE S3 Protein panel identifications from secretomes of aggressive (anaplastic-derived) and non-aggressive (papillary-derived) TC cell lines

TABLE S4 Combined ALCAM and AXL sera expression in relation to clinico-pathological parameters using ELISA

TABLE S5 Summary of patient tissue specimen information used for immunohistochemistry

Figure S1. Ingenuity Pathway Analysis reveals several important protein-protein interactions of identified secretome proteins. The network generated suggests several extracellular secretome proteins (labelled in red and highlighted in yellow) interact with cytoplasmic proteins via membrane-bound receptors such as EGFR, L1CAM, and NGFR. Furthermore, AXL interacts with GRB2 and SRC, both intermediates of EGFR signalling pathways. 14-3-3 zeta (YWHAZ) was also observed to be a potential central cytoplasmic hub mediating interactions between many of the secretome proteins and EGFR-signalling pathways. ALCAM was found to have interactions with L1CAM and NGFR, and indirect associations to the EGFR-activated pathways. From this network, 14-3-3 zeta, APLP2, APP, ALCAM, AXL, hnRNP K, PGK1, PKM2, and SET were selected for further analysis in sera and/or tissues of thyroid cancer patients. Bold lines represent direct protein-protein interactions and dashed lines represent indirect interactions.

Figure S2. Receiver operating characteristics curves for secretome protein IHC tissue scores. Green diagonal lines represent reference lines.

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