Supplementary Materials

Web Extra Materials Tissue Core 3 µM Section Tissue Microarray Slide Supplementary Figure S1. Process of tissue microarray construction. Representative areas of the tumor were identified by a pathologist on H&E stained sections. Reference histological slides with the specific area marked by the pathologist were aligned with the respective donor block. The corresponding areas were marked on paraffin blocks and three parallel tissue cores were obtained per tumor to account for intratumoral heterogeneity. Tissue arrays were constructed by placing 1 mm diameter cores in recipient paraffin blocks using a tissue arrayer (Galileo TMA CK3500 Tissue Micro arrayer; ISETMA Software, Integrated System Engineering, Milan, Italy), and limited to 72 cores per recipient block. Then, consecutive sections (with a thickness of 3 μm) were cut from each TMA block, and mounted on microscope slides. Finally, the unstained slides were deparaffinized and rehydratedand using standard methods, and immunohistochemically assayed. 1 cancer Breast cancer Cervical cancer Colorectal cancer Endometrial Glioma cancer neck and Head cancer Liver cancer Lung Melanoma cancer Ovarian cancer Pancreatic cancer Prostate cancer Renal cancer Stomach cancer Testis cancer Thyroid cancer Urothelial ABCB1 0.6 0.3 4.6 0.6 2.7 0.2 7.8 0.3 0.2 0.2 2.3 1.5 7.1 0.9 0.5 0.8 0.3 ANO7 0.3 0.3 0.8 0.6 0.3 0.2 0.4 0.4 0.4 0.1 0.6 27 0.5 0.8 0.5 0.4 0.3 AQP5 0.4 1.9 0.1 53.8 2.4 0.2 0 1.7 0.3 21.3 20.8 0.2 0 3.9 1.8 4.5 0.1 ATP2B2 0 0 0 0.4 3.2 0 6.7 0 0 0.9 0 0 0.8 0 0 0 0 CD19 0.2 0.3 0.3 0.4 0.1 0.2 0.1 0.9 0.1 0.3 0.3 0.1 0.1 0.7 1.9 0.1 0.2 CD276 23 14.8 16.5 26.7 25.2 25 8.9 20.9 30.1 17.9 22.8 21.6 13.6 15.7 20.3 13.2 20 CD79B 1.4 0.9 0.9 1 0.3 0.9 1 2.3 1.1 0.6 1.7 1 2 1.2 2.9 1.3 0.8 CDCP1 8.5 19 16.3 12.3 1.4 22 0.1 12.3 1.4 8.9 16.3 5 4.3 16.2 2.6 9.8 12.1 CNR1 0.1 0 0 0 8.7 0 0 0.4 0 0.1 0.4 0.1 0.2 0.2 0.4 0.1 0.1 ERBB2 34.9 22.2 23.7 23.1 5.9 14.3 7.2 19.1 7.5 18.9 23.1 26.2 15.4 22 7.3 30.4 35.2 GPBAR1 0.2 0.1 0.6 0.3 0.2 0.2 0.3 0.2 0.2 0.4 2.9 0.2 0.4 1.3 0.5 0.2 0.3 HTR2B 0.5 0.2 0.1 0.7 0.1 0.1 0.3 0.4 0.2 0.4 1.3 0.1 0.4 0.4 0.2 0.4 0.2 ITGA3 8.7 25 13.3 11.1 7.1 49 0.8 29.9 31.6 22.2 42.4 6.3 36.1 21.5 2.2 82.2 38.4 MS4A1 0.3 0.2 0.2 0.1 0 0.2 0.1 0.9 0 0 0.4 0.1 0.1 0.8 1 0.1 0.1 MSLN 0.2 23.9 13.6 17.5 0.5 1.5 0 7.5 0.1 290.9 89.7 0.4 0.5 19.7 0.2 0.2 0.4 MUC16 0.1 1 0 2.7 0 0.1 0 0.2 0 14.2 0.7 0 0 0 0.1 0 0 NECTIN4 21 46.2 5.2 12 0.1 33.1 0.1 21.9 0.7 6.6 15.5 10.2 0.1 4.3 2.3 8.7 53.3 PCDH7 1.5 2.9 0.6 4.4 1.2 4 0 1.6 5.9 3.2 3.4 1.3 0.2 3.2 0.6 2.1 1.1 SIT1 1.1 1.4 1.5 1 0.3 1.2 0.5 2 0.7 1 1.2 0.6 1.4 2 3.9 0.6 0.7 SLC2A14 0 0 0 0 0.1 0 0 0.1 0 0.1 0.1 0 0.1 0 3.9 0 0 SLC39A10 6 3.1 5.6 5.5 8.4 2.8 1.1 5.4 3.5 8.6 4.7 7.9 5.5 4.2 10.4 19.1 3.5 SLC6A6 6.9 4.5 13.4 10 2.7 6.5 0.6 11.5 4.6 4.7 15.3 1.6 6.9 8.9 11.2 8.3 6.9 UPK1B 0 0.1 0 5.2 0 0.5 0 0.3 0 4.2 1.8 0 0.4 0.2 0.1 0 62.3 Supplementary Figure S2. A heat map depicting the FPKM values for candidate ADC targets across 17 tumor types 2 Supplementary Methods S1. HPA-based criteria for validation steps The immunostaining result of each antibody is compared with available gene/RNA/protein characterization data, resulting in different validations: Literature conformity and RNA consistency. Literature conformity: Literature conformity refers to the conformance of the expression pattern to available gene/protein characterization data in scientific literature and data from bioinformatic predictions. UniProt is used as the main source of gene/protein characterization data and when relevant, available publications and other sources of information are probed in depth. Extensive or sufficient gene/protein data requires that there is evidence of existence on a protein level and that a substantial quantity of published experimental data is available from literature and public databases. Limited protein/gene data does not require evidence of existence on a protein level and refers to genes for which only bioinformatic predictions and scarce published experimental data is available. The different options of literature conformity are: Consistent with extensive gene/protein characterization data Consistent with gene/protein characterization data Partly consistent with extensive gene/protein characterization data Partly consistent with gene/protein characterization data No available gene/protein characterization data Not consistent with gene/protein characterization data RNA consistency: RNA consistency is based on a comparison of antibody staining in 44 normal tissues with RNA-seq data combined from HPA, GTEX and FANTOM. RNA consistency is scored as follows: 3 Consistent with RNA expression data Mainly consistent with RNA expression data Mainly not consistent with RNA expression data Not consistent with RNA expression data No internal RNA expression data available for correlation Verification of membrane localization: In addition to RNA consistency and literature conformity, verification of membrane localization were considered for expression validation of potential targets. As stated in the methods section, the IHC images and description of the staining pattern (available at the HPA database) for each antibody in cancer tissues were considered for verification of membrane localization. A predominant membranous staining in IHC samples was required for each potential target to pass the validation process. Only potential targets that passed three HPA-based validation steps were considered as candidate targets. 4 Supplementary Table S1.

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