{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:55:09Z","timestamp":1790949309499,"version":"4.1.0"},"reference-count":16,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Blood-based proteomics may complement existing MCED approaches by capturing tumor-secreted proteins and systemic host responses. We reviewed prospective and multicancer studies published from 2020 to 2025 that used Olink, SomaScan, or mass spectrometry and compared evidence from case\u2013control and prospective designs. Candidate proteins were classified as established or novel and evaluated using pathway and cancer-hallmark enrichment analyses, GEPIA3.0 Cox analyses, TCGA Kaplan\u2013Meier survival curves, and TPCPA\/RPPA protein abundance data. Across platforms, established markers, including CEACAM5, WFDC2\/HE4, and GDF15 were complemented by novel candidates converging on a matrix\u2013immune\u2013secretory axis. This axis included MMP12 and ADAM8, CD74 and CXCL13, TGFB1, and CDCP1. Secretory and matrix-associated candidates were linked to poorer survival in several epithelial cancers, whereas immune-associated proteins showed context-dependent effects. Tumor-type-specific protein elevation supported their detectability, and interaction analysis organized the candidates into biologically coherent modules. These findings support an MCED framework combining higher-risk secretory and matrix markers with immune-context indicators to improve sensitivity and biological interpretation. Prospective validation and down-selection into scalable targeted assays are required before population-level application.<\/jats:p>","DOI":"10.1021\/acs.jproteome.6c00526","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:44:55Z","timestamp":1788353095000},"page":"5025-5038","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Proteomic\nSignatures for Multicancer Early\nDetection: Cross-Platform Evidence for a Matrix\u2013Immune\u2013Secretory\nBiomarker Axis"],"prefix":"10.1021","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6483-0802","authenticated-orcid":true,"given":"Vivek","family":"Singh","sequence":"first","affiliation":[{"name":"King George\u2019s Medical University , , , ,","place":["Lucknow, Uttar Pradesh, India, 226003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipin","family":"Kumar","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institute of Health , , 9000 Rockville Pike , , ,","place":["Bethesda, Maryland, United States, 20892"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidushi","family":"Singh","sequence":"additional","affiliation":[{"name":"Dr. Ram Manohar Lohia Institute of Medical Sciences , , , ,","place":["Lucknow, Uttar Pradesh, India, 226010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Kushwaha","sequence":"additional","affiliation":[{"name":"King George\u2019s Medical University , , , ,","place":["Lucknow, Uttar Pradesh, India, 226003"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"issue":"1","key":"2026100208413876700_cit1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjonc-2023-000073","article-title":"Novel Proteomics-Based\nPlasma Test for Early Detection of Multiple Cancers in the General\nPopulation","volume":"3","author":"Budnik","year":"2024","journal-title":"BMJ. Oncol."},{"issue":"6779","key":"2026100208413876700_cit2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adx2678","article-title":"A Human Pan-Disease Blood Atlas of the Circulating\nProteome","volume":"390","author":"A\u0301lvez","year":"2025","journal-title":"Science"},{"issue":"10409","key":"2026100208413876700_cit3","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1016\/S0140-6736(23)01700-2","article-title":"Blood-Based\nTests for Multicancer\nEarly Detection (PATHFINDER): A Prospective Cohort Study","volume":"402","author":"Schrag","year":"2023","journal-title":"Lancet"},{"issue":"1","key":"2026100208413876700_cit4","doi-asserted-by":"publisher","DOI":"10.1038\/s43856-025-00945-0","article-title":"Deep Plasma Proteomics\nIdentifies and Validates an Eight-Protein Biomarker Panel That Separate\nBenign from Malignant Tumors in Ovarian Cancer","volume":"5","author":"Moskov","year":"2025","journal-title":"Commun. Med."},{"issue":"1","key":"2026100208413876700_cit5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48017-6","article-title":"Identifying Proteomic Risk Factors for Cancer Using\nProspective and Exome Analyses of 1463 Circulating Proteins and Risk\nof 19 Cancers in the UK Biobank","volume":"15","author":"Papier","year":"2024","journal-title":"Nat. Commun."},{"issue":"9","key":"2026100208413876700_cit6","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1038\/s41591-024-03142-z","article-title":"Proteomic\nSignatures Improve Risk Prediction for Common and Rare Diseases","volume":"30","author":"Carrasco-Zanini","year":"2024","journal-title":"Nat. Med."},{"issue":"6","key":"2026100208413876700_cit7","doi-asserted-by":"publisher","first-page":"3846","DOI":"10.21037\/tcr-2025-272","article-title":"Development and Clinical\nApplications of Liquid Biopsy Assays in Cancer Screening","volume":"14","author":"Han","year":"2025","journal-title":"Transl. Cancer Res."},{"issue":"8","key":"2026100208413876700_cit8","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1158\/1940-6207.CAPR-23-0451","article-title":"Outcomes Following\na False-Positive Multi-Cancer Early Detection Test: Results from DETECT-A,\nthe First Large, Prospective, Interventional MCED Study","volume":"17","author":"Lennon","year":"2024","journal-title":"Cancer Prev. Res."},{"issue":"6378","key":"2026100208413876700_cit9","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1126\/science.aar3247","article-title":"Detection\nand Localization of Surgically Resectable Cancers with a Multi-Analyte\nBlood Test","volume":"359","author":"Cohen","year":"2018","journal-title":"Science"},{"issue":"6","key":"2026100208413876700_cit10","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.112617","article-title":"Multi-Analyte Approach\nCombining\nCfDNA Sequencing and Protein Testing for Early Ovarian Cancer Detection","volume":"28","author":"Wang","year":"2025","journal-title":"iScience"},{"key":"2026100208413876700_cit11","doi-asserted-by":"crossref","unstructured":"Gainullin, V.; Manesse, M.; Zhuang, F.; Gray, M.; Hwang, H. J.; Cerqueira, G. C.; Nobles, C. L.; Kumar, M.; Arvai, K.; Chen, X.; Tyson, C. C.; Ji, C.; Bae, J.; Guthrie, V. B.; Kaur, J.; Katerov, V. E.; Hogstrom, L.; Hagmann, L.; Uren, P. J.; Garces, J.; Allawi, H. T.; Fa, V.; McElhinny, A.; Silvestri, G. A.; Chesla, D.; Given, R. W.; Beer, T. M.; Diehl, F.\n          Performance of a Multi-Target, Multi-Cancer\nEarly Detection (MCED) Blood Test in a Prospectively Collected Cohort\n          2025\n          10.1101\/2025.08.24.25334244.","DOI":"10.1101\/2025.08.24.25334244"},{"key":"2026100208413876700_cit12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104686","article-title":"Plasma Protein Biomarkers\nfor Early\nPrediction of Lung Cancer","volume":"93","author":"Davies","year":"2023","journal-title":"eBioMedicine"},{"key":"2026100208413876700_cit13","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2025.118291","article-title":"Recent Progress in Mass Spectrometry-Based\nLiquid Biopsy for Cancer Detection and Analysis: A Comprehensive Review","volume":"190","author":"Lu","year":"2025","journal-title":"TrAC, Trends Anal. Chem."},{"key":"2026100208413876700_cit14","doi-asserted-by":"publisher","first-page":"S93","DOI":"10.1016\/j.htct.2024.02.016","article-title":"Exploring\nNovel Protein Biomarkers\nfor Early-Stage Diagnosis and Prognosis of T-Acute Lymphoblastic Leukemia\n(T-ALL)","volume":"46","author":"Singh","year":"2024","journal-title":"Hematol. Transfus. Cell Ther."},{"issue":"2","key":"2026100208413876700_cit15","doi-asserted-by":"publisher","DOI":"10.1016\/j.retram.2026.103585","article-title":"Role of IGF2BP3\nas a Prognostic Biomarker in Chronic Myeloid Leukemia Progression\nand Disease Stratification","volume":"74","author":"Chauhan","year":"2026","journal-title":"Curr. Res. Transl.\nMed."},{"key":"2026100208413876700_cit16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlb.2025.100324","article-title":"Next-Generation\nLeukemia Diagnostics: Integrating LC-MS\/MS Proteomics with Liquid\nBiopsy Platforms","volume":"9","author":"Singh","year":"2025","journal-title":"J. Liq. Biopsy"}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jproteome.6c00526","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/10\/5025\/67747930\/acs.jproteome.6c00526.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/10\/5025\/67747930\/acs.jproteome.6c00526.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:10:49Z","timestamp":1790946649000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/25\/10\/5025\/5362051\/Circulating-Proteomic-Signatures-for-Multicancer"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,29]]},"references-count":16,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,8,29]]},"published-print":{"date-parts":[[2026,10,2]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jproteome.6c00526","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,29]]}}}