{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:03:23Z","timestamp":1792569803371,"version":"4.5.0"},"reference-count":79,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The relatively recent developments in mass spectrometry (MS) have provided novel opportunities for this technology to impact modern medicine. One of those opportunities is in biomarker discovery and diagnostics. Key developments in sample preparation have enabled a greater range of clinical samples to be characterized at a deeper level using MS. While most of these developments have focused on blood, tissues have also been an important resource. Fresh tissues, however, are difficult to obtain for research purposes and require significant resources for long-term storage. There are millions of archived formalin-fixed paraffin-embedded (FFPE) tissues within pathology departments worldwide representing every possible tissue type including tumors that are rare or very small. Owing to the chemical technique used to preserve FFPE tissues, they were considered intractable to many newer proteomics techniques and primarily only useful for immunohistochemistry. In the past couple of decades, however, researchers have been able to develop methods to extract proteins from FFPE tissues in a form making them analyzable using state-of-the-art technologies such as MS and protein arrays. This review will discuss the history of these developments and provide examples of how they are currently being used to identify biomarkers and diagnose diseases such as cancer.<\/jats:p>","DOI":"10.3390\/biom13010096","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T05:02:30Z","timestamp":1672808550000},"page":"96","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Biomarker Analysis of Formalin-Fixed Paraffin-Embedded Clinical Tissues Using Proteomics"],"prefix":"10.3390","volume":"13","author":[{"given":"Ekenedirichukwu N.","family":"Obi","sequence":"first","affiliation":[{"name":"School of Pharmacy, Cedarville University, Cedarville, OH 45314, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Tellock","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Cedarville University, Cedarville, OH 45314, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel J.","family":"Thomas","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Cedarville University, Cedarville, OH 45314, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Veenstra","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Cedarville University, Cedarville, OH 45314, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1021\/ac034869m","article-title":"Ultra-high-efficiency strong cation exchange LC\/RPLC\/MS\/MS for high dynamic range characterization of the human plasma proteome","volume":"76","author":"Shen","year":"2002","journal-title":"Anal. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/s41586-020-2402-x","article-title":"The proteome landscape of the kingdoms of life","volume":"582","author":"Geyer","year":"2020","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1074\/mcp.M300031-MCP200","article-title":"Characterization of the low molecular weight human serum proteome","volume":"2","author":"Tirumalai","year":"2003","journal-title":"Mol. Cell. Proteom."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"104099","DOI":"10.1016\/j.jprot.2020.104099","article-title":"Comprehensive serum proteomic analysis in early endometrial cancer","volume":"234","author":"Uyar","year":"2021","journal-title":"J. Proteom."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e2100330","DOI":"10.1002\/pmic.202100330","article-title":"Targeted proteomics on its way to discovery","volume":"22","author":"Mendes","year":"2022","journal-title":"Proteomics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1074\/mcp.R200007-MCP200","article-title":"The human plasma proteome: History, character, and diagnostic prospects","volume":"1","author":"Anderson","year":"2002","journal-title":"Mol. Cell. Proteom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.4155\/bio-2019-0145","article-title":"Plasma\/serum proteomics: Depletion strategies for reducing high-abundance proteins for biomarker discovery","volume":"11","author":"Lee","year":"2019","journal-title":"Bioanalysis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1039\/D0MO00072H","article-title":"Data-independent acquisition mass spectrometry (DIA-MS) for proteomic applications in oncology","volume":"17","author":"Krasny","year":"2021","journal-title":"Mol. Omics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1373\/clinchem.2009.127019","article-title":"The bottleneck in the cancer biomarker pipeline and protein quantification through mass spectrometry-approaches: Current strategies for candidate verification","volume":"56","author":"Makawita","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2100153","DOI":"10.1002\/pmic.202100153","article-title":"Targeted liquid chromatography-tandem mass spectrometry analysis of proteins: Basic principles, applications, and perspectives","volume":"21","author":"Kulyyassov","year":"2021","journal-title":"Proteomics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1021\/ac902204k","article-title":"Combined blood\/tisse analysis for cancer biomarker discovery: Application to renal cell carcinoma","volume":"82","author":"Wei","year":"2010","journal-title":"Anal. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1158\/1055-9965.EPI-20-0074","article-title":"Pitfalls in cancer biomarker discovery and validation with emphasis on circulating tumor DNA","volume":"29","author":"Ren","year":"2020","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1559-0275-10-13","article-title":"Translation of proteomic biomarkers into FDA approved cancer diagnostics: Issues and challenges","volume":"10","author":"Levin","year":"2013","journal-title":"Clin. Proteom."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4419","DOI":"10.1038\/s41598-022-08430-7","article-title":"Temporal dynamics from phosphoproteomics using endoscopic biopsy specimens provides new therapeutic targets in stage IV gastric cancer","volume":"12","author":"Hirano","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"761225","DOI":"10.3389\/fimmu.2022.761225","article-title":"A systematic review of tissue and single cell transcriptome\/proteome studies of the brain in multiple sclerosis","volume":"13","author":"Elkjaer","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"993781","DOI":"10.3389\/fonc.2022.993781","article-title":"Advances in the application of proteomics in lung cancer","volume":"12","author":"Ling","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"229","DOI":"10.2144\/000114414","article-title":"Analysis of formalin-fixed, paraffin-embedded (FFPE) tissue via proteomic techniques and misconceptions of antigen retrieval","volume":"60","author":"Padula","year":"2016","journal-title":"Biotechniques"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1177\/33.8.3894502","article-title":"Formaldehyde fixation","volume":"33","author":"Fox","year":"1985","journal-title":"J. Histochem. Cytochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/sj.onc.1209755","article-title":"Direct cancer tissue proteomics: A method to identify candidate cancer biomarkers from formalin-fixed paraffin-embedded archival tissues","volume":"26","author":"Hwang","year":"2007","journal-title":"Oncogene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1074\/mcp.M500102-MCP200","article-title":"Proteomic analysis of formalin-fixed prostate tissue","volume":"4","author":"Hood","year":"2005","journal-title":"Mol. Cell. Proteom."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4179","DOI":"10.1021\/acs.jproteome.0c00354","article-title":"Phosphorylation ratio determination in fresh-frozen and formalin-fixed paraffin-embedded tissue with target mass spectrometry","volume":"19","author":"Zeneyedpour","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1586\/epr.13.3","article-title":"Proteomics studies of formalin-fixed paraffin-embedded tissues","volume":"10","author":"Giusti","year":"2013","journal-title":"Expert Rev. Proteom."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3108","DOI":"10.1002\/pmic.201000082","article-title":"mTRAQ-based quantification of potential endometrial carcinoma biomarkers from archived formalin-fixed paraffin-embedded tissues","volume":"10","author":"DeSouza","year":"2010","journal-title":"Proteomics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1021\/pr300130t","article-title":"Precision of multiple reaction monitoring mass spectrometry analysis of formalin-fixed paraffin-embedded tissue","volume":"11","author":"Sprung","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1021\/acs.jproteome.0c00850","article-title":"Proteomic workflows for high-quality quantitative proteome and post-translational modification analysis of clinically relevant samples from formalin-fixed paraffin-embedded archives","volume":"20","author":"Kuras","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1177\/002215540104900801","article-title":"Antigen retrieval techniques: Current perspectives","volume":"49","author":"Shi","year":"2001","journal-title":"J. Histochem. Cytochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1021\/acs.jproteome.9b00587","article-title":"Proteomics analysis of formalin fixed paraffin embedded tissues in the investigation of prostate cancer","volume":"19","author":"Mantsiou","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4710","DOI":"10.1021\/pr1004168","article-title":"Formalin-fixed paraffin-embedd (FFPE) proteome analysis using gel-free and gel-based proteomics","volume":"9","author":"Azimzadeh","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1021\/acs.jproteome.9b00671","article-title":"Accelerated protein biomarker discovery from FFPE tissue samples using single-shot, short gradient microflow SWATH-MS","volume":"19","author":"Sun","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/prca.201200064","article-title":"Improved protein extraction and protein identification from archival formalin-fixed paraffin-embedded human aortas","volume":"7","author":"Fu","year":"2013","journal-title":"Proteom. Clin. Appl."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1002\/pmic.200800971","article-title":"Generation of high-quality protein extracts from formalin-fixed, paraffin-embedded tissues","volume":"9","author":"Addis","year":"2009","journal-title":"Proteomics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11271","DOI":"10.1038\/s41598-020-68245-2","article-title":"Establishet ad validation of highly accurate formalin-fixed paraffin-embedded quantitative proteomics by heat-compatible pressure cycling technology using phase-transfer surfactant and SWATH-MS","volume":"10","author":"Uchida","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4172\/jpb.1000315","article-title":"Improving the proteomic analysis of archival tissue by using pressure-assisted protein extraction: A mechanistic approach","volume":"7","author":"Fowler","year":"2014","journal-title":"J. Proteom. Bioinform."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0022-2836(03)00209-2","article-title":"Pressure-dependent changes in the solution structure of hen egg-white lysozyme","volume":"327","author":"Refaee","year":"2003","journal-title":"J. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1002\/pro.5560071020","article-title":"Probing the contribution of internal cavities to the volume change of protein unfolding under pressure","volume":"7","author":"Frye","year":"1998","journal-title":"Protein Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1110\/ps.8.12.2765","article-title":"Effect of hydrostatic pressure on unfolding of alphalactalbumin: Volumetric equivalence of the molten globule and unfolded state","volume":"8","author":"Kobashigawa","year":"1999","journal-title":"Protein Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/labinvest.3700596","article-title":"\u2018Tissue surrogates\u2019 as a model for archival formalin-fixed paraffin-embedded tissues","volume":"87","author":"Fowler","year":"2007","journal-title":"Lab. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/labinvest.3700708","article-title":"Elevated hydrostatic pressure promotes protein recovery from formalin-fixed, paraffin-embedded tissue surrogates","volume":"88","author":"Fowler","year":"2008","journal-title":"Lab. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Fowler, C.B., Chesnick, I.E., Moore, C.D., O\u2019Leary, T.J., and Mason, J.T. (2010). Elevated pressure improves the extraction and identification of proteins recovered from formalin-fixed paraffin-embedded tissue surrogates. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014253"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1074\/mcp.M800518-MCP200","article-title":"Equivalence of protein inventories obtained from formalin-fixed paraffin-embedded and frozen tissue in multidimensional liquid chromatography-tandem mass spectrometry shotgun proteomic analysis","volume":"8","author":"Sprung","year":"2009","journal-title":"Mol. Cell. Proteom."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"34949","DOI":"10.1038\/srep34949","article-title":"Quantitative profiling of single formalin fixed tumor sections: Proteomics for translational research","volume":"6","author":"Hughes","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e2100147","DOI":"10.1002\/pmic.202100147","article-title":"A prostate cancer tissue specific spectral library for targeted proteomic analysis","volume":"22","author":"Sun","year":"2022","journal-title":"Proteomics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"240","DOI":"10.3390\/proteomes1030240","article-title":"Proteomic analysis of matched formalin-fixed, paraffin-embedded specimens in patients with advanced serous ovarian carcinoma","volume":"1","author":"Smith","year":"2013","journal-title":"Proteomes"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1074\/mcp.RA117.000189","article-title":"Spatial tissue proteomics quantifies inter- and intratumor heterogeneity in hepatocellular carcinoma (HCC)","volume":"17","author":"Buczak","year":"2018","journal-title":"Mol. Cell. Proteom."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1038\/s41467-021-23855-w","article-title":"Comprehensive micro-scaled proteome and phosphoproteome characterization of archived retrospective cancer repositories","volume":"12","author":"Friedich","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1074\/mcp.M116.062414","article-title":"Unlocking cancer glycomes from histopathological formalin-fixed paraffin-embedded (FFPE) tissue microdissections","volume":"16","author":"Hinneburg","year":"2017","journal-title":"Mol. Cell. Proteom."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lygirou, V., Fasoulakis, K., Stroggilos, R., Makridakis, M., Latosinska, A., Frantzi, M., Katafigiotis, I., Alamanis, C., Stravodimos, K.G., and Constantinides, C.A. (2022). Proteomic analysis of prostate cancer FFPE samples reveals markers of disease progression and aggressiveness. Cancers, 14.","DOI":"10.3390\/cancers14153765"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1369\/jhc.7A7177.2007","article-title":"Proteome analysis of microdissected formalin-fixed and paraffin-embedded tissue specimens","volume":"55","author":"Guo","year":"2007","journal-title":"J. Histochem. Cytochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1021\/pr0605318","article-title":"Development of efficient protein extraction methods for shotgun proteome analysis of formalin-fixed tissues","volume":"6","author":"Jiang","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1002\/1878-0261.12570","article-title":"High-throughput proteomic analysis of FFPE tissue samples facilitates tumor stratification","volume":"13","author":"Zhu","year":"2019","journal-title":"Mol. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jang, H.N., Moon, S.J., Jung, K.C., Kim, S.W., Kim, H., Han, D., and Kim, J.H. (2021). Mass spectrometry-based proteomics discovery of prognostic biomarkers in adrenal cortical carcinoma. Cancers, 13.","DOI":"10.3390\/cancers13153890"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e1900036","DOI":"10.1002\/prca.201900036","article-title":"Quantitative proteomics for monitoring renal transplant injury","volume":"14","author":"Song","year":"2020","journal-title":"Proteom. Clin. Appl."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.jprot.2014.08.013","article-title":"Comparison of two FFPE preparation methods using label-free shotgun proteomics: Applicatin to tissue of diverticulitis patients","volume":"112","author":"Bertrand","year":"2015","journal-title":"J. Proteom."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"104686","DOI":"10.1016\/j.jprot.2022.104686","article-title":"Comparative proteomics analysis of human FFPE testicular tissues reveals new candidate biomarkers for distinction among azoospermia types and subtypes","volume":"267","author":"Davalieva","year":"2022","journal-title":"J. Proteom."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1158\/1078-0432.CCR-07-1497","article-title":"Proteomic analysis of laser-captured paraffin-embedded tissues: A molecular portrait of head and neck cancer progression","volume":"14","author":"Patel","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1021\/pr101073s","article-title":"Differential proteomic analysis of late-stage and recurrent breast cancer from formalin-fixed paraffin-embedded tissues","volume":"10","author":"Bateman","year":"2001","journal-title":"J. Proteome Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"15456","DOI":"10.1038\/srep15456","article-title":"Proteomic analysis of neurons microdissected from formalin-fixed, paraffin-embedded Alzheimer\u2019s disease brain tissue","volume":"5","author":"Drummond","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1074\/mcp.RA119.001889","article-title":"Quantitative profiling of the human substantia nigra proteome from laser-capture microdissected FFPE tissue","volume":"19","author":"Griesser","year":"2020","journal-title":"Mol. Cell. Proteom."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1021\/acs.jproteome.7b00913","article-title":"Extending the compatibility of the SP3 paramagnetic bead processing approach for proteomics","volume":"4","author":"Moggridge","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1021\/ac0262560","article-title":"Tandem mass tags: A novel quantification strategy for comparative analysis of complex protein mixtures by MS\/MS","volume":"75","author":"Thompson","year":"2003","journal-title":"Anal. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1038\/s41467-022-28524-0","article-title":"Proteomic analysis of archival breast cancer clinical specimens identifies biological subtypes with distinct survival outcomes","volume":"13","author":"Asleh","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"61","DOI":"10.4137\/BIC.S9455","article-title":"Molecular profiling for breast cancer: A comprehensive review","volume":"5","author":"Kittaneh","year":"2013","journal-title":"Biomark. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Li, S., Bao, C., Huang, L., and Wei, J.-F. (2022). Current therapeutic strategies for metastatic triple-negative breast cancer: From pharmacists\u2019 perspective. J. Clin. Med., 11.","DOI":"10.3390\/jcm11206021"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1177\/39.6.1709656","article-title":"Antigen retrieval in formalin-fixed, paraffin-embedded tissues: An enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections","volume":"39","author":"Shi","year":"1991","journal-title":"J. Histochem. Cytochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.cca.2021.12.017","article-title":"Roles of MET in human cancer","volume":"525","author":"Yang","year":"2022","journal-title":"Clin. Chem. Acta"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Catenacci, D.V.T., Liao, W.-L., Thyparambil, S., Henderson, L., Xu, P., Zhao, L., Rambo, B., Hart, J., Xiao, S.-Y., and Bengali, K. (2014). Absolute quantitation of Met using mass spectrometry for clinical application: Assay precision, stability, and correlation with MET gene amplification in FFPE tumor tissue. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100586"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1093\/clinchem\/hvaa178","article-title":"Clinical application of multiple reaction monitoring-mass spectrometry to human epidermal growth factor receptor 2 measurements as a potential diagnostic tool for breast cancer therapy","volume":"66","author":"Do","year":"2020","journal-title":"Clin. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/978-1-4939-9164-8_13","article-title":"Development of a highly multiplexed SRM assay for biomarker discovery in formalin-fixed paraffin-embedded tissues","volume":"1959","author":"Steiner","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s00726-013-1494-0","article-title":"Analysis of the formalin-fixed paraffin-embedded tissue proteome: Pitfalls, challenges, and future prospectives","volume":"45","author":"Maes","year":"2013","journal-title":"Amino Acids"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.jprot.2012.09.033","article-title":"Comparability of differential proteomics data generated from paired archival fresh-frozen and formalin-fixed samples by GeLC-MS\/MS and spectral counting","volume":"77","author":"Tanca","year":"2012","journal-title":"J. Proteom."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/prca.201200065","article-title":"Proteomic analysis of formalin-fixed paraffin-embedded renal tissue samples by label-free MS: Assessment of overall technical variability and the impact of block age","volume":"7","author":"Craven","year":"2013","journal-title":"Proteom. Clin. Appl."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12014-018-9202-4","article-title":"Residual tissue repositories as a resource for population-based cancer proteomic studies","volume":"15","author":"Piehowski","year":"2018","journal-title":"Clin. Proteom."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1002\/path.5420","article-title":"A streamlined mass spectrometry-based proteomics workflow for large-scale FFPE tissue analysis","volume":"251","author":"Coscia","year":"2020","journal-title":"J. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"622855","DOI":"10.3389\/pore.2021.622855","article-title":"Evaluation of protein purification techniques and effects of storage duration on LC-MS\/MS analysis of archived FFPE human CRC tissues","volume":"27","author":"Rossouw","year":"2021","journal-title":"Pathol. Oncol. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1021\/bc050340f","article-title":"Identification of formaldehyde-induced modifications in proteins: Reactions with insulin","volume":"17","author":"Metz","year":"2006","journal-title":"Bioconjugate Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/labinvest.2016.134","article-title":"Characterization of histone-related chemical modifications in formalin-fixed paraffin-embedded and fresh-frozen human pancreatic cancer xenografts using LC-MS\/MS","volume":"97","author":"Bauden","year":"2017","journal-title":"Lab. Investig."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1093\/jnci\/djs438","article-title":"Quantitative assessment of effect of preanalytic cold ischemic time on protein expression in breast cancer tissue","volume":"104","author":"Neumeister","year":"2012","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/prca.200800005","article-title":"A well-based reverse-phase protein array applicable to extracts from formalin-fixed paraffing-embedded tissue","volume":"2","author":"Chung","year":"2008","journal-title":"Proteom. Clin. Appl."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1080\/10520295.2018.1446101","article-title":"Factors that drive the increasing use of FFPE tissue in basic and translational cancer research","volume":"93","author":"Gaffney","year":"2018","journal-title":"Biotech. 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