PMID- 36228107 OWN - NLM STAT- MEDLINE DCOM- 20230412 LR - 20240305 IS - 1615-9861 (Electronic) IS - 1615-9853 (Print) IS - 1615-9853 (Linking) VI - 23 IP - 7-8 DP - 2023 Apr TI - Data-independent acquisition and quantification of extracellular matrix from human lung in chronic inflammation-associated carcinomas. PG - e2200021 LID - 10.1002/pmic.202200021 [doi] LID - 2200021 AB - Early events associated with chronic inflammation and cancer involve significant remodeling of the extracellular matrix (ECM), which greatly affects its composition and functional properties. Using lung squamous cell carcinoma (LSCC), a chronic inflammation-associated cancer (CIAC), we optimized a robust proteomic pipeline to discover potential biomarker signatures and protein changes specifically in the stroma. We combined ECM enrichment from fresh human tissues, data-independent acquisition (DIA) strategies, and stringent statistical processing to analyze "Tumor" and matched adjacent histologically normal ("Matched Normal") tissues from patients with LSCC. Overall, 1802 protein groups were quantified with at least two unique peptides, and 56% of those proteins were annotated as "extracellular." Confirming dramatic ECM remodeling during CIAC progression, 529 proteins were significantly altered in the "Tumor" compared to "Matched Normal" tissues. The signature was typified by a coordinated loss of basement membrane proteins and small leucine-rich proteins. The dramatic increase in the stromal levels of SERPINH1/heat shock protein 47, that was discovered using our ECM proteomic pipeline, was validated by immunohistochemistry (IHC) of "Tumor" and "Matched Normal" tissues, obtained from an independent cohort of LSCC patients. This integrated workflow provided novel insights into ECM remodeling during CIAC progression, and identified potential biomarker signatures and future therapeutic targets. CI - (c) 2022 The Authors. Proteomics published by Wiley-VCH GmbH. FAU - Bons, Joanna AU - Bons J AD - Buck Institute for Research on Aging, Novato, California, USA. FAU - Pan, Deng AU - Pan D AD - Department of Pathology, University of California, San Francisco, California, USA. FAU - Shah, Samah AU - Shah S AD - Buck Institute for Research on Aging, Novato, California, USA. FAU - Bai, Rosemary AU - Bai R AD - Department of Pathology, University of California, San Francisco, California, USA. FAU - Chen-Tanyolac, Chira AU - Chen-Tanyolac C AD - Department of Pathology, University of California, San Francisco, California, USA. FAU - Wang, Xianhong AU - Wang X AD - Department of Pathology, University of California, San Francisco, California, USA. FAU - Elliott, Daffolyn R Fels AU - Elliott DRF AD - Department of Pathology, University of California, San Francisco, California, USA. FAU - Urisman, Anatoly AU - Urisman A AD - Department of Pathology, University of California, San Francisco, California, USA. FAU - O'Broin, Amy AU - O'Broin A AD - Buck Institute for Research on Aging, Novato, California, USA. FAU - Basisty, Nathan AU - Basisty N AUID- ORCID: 0000-0001-6173-1139 AD - Buck Institute for Research on Aging, Novato, California, USA. FAU - Rose, Jacob AU - Rose J AD - Buck Institute for Research on Aging, Novato, California, USA. FAU - Sangwan, Veena AU - Sangwan V AD - Division of Thoracic and Upper Gastrointestinal Surgery, Montreal General Hospital, McGill University Health Centre, Montreal, Quebec, Canada. FAU - Camilleri-Broet, Sophie AU - Camilleri-Broet S AD - Department of Pathology, McGill University, Montreal, Quebec, Canada. FAU - Tankel, James AU - Tankel J AD - Division of Thoracic and Upper Gastrointestinal Surgery, Montreal General Hospital, McGill University Health Centre, Montreal, Quebec, Canada. FAU - Gascard, Philippe AU - Gascard P AD - Department of Pathology, University of California, San Francisco, California, USA. FAU - Ferri, Lorenzo AU - Ferri L AD - Division of Thoracic and Upper Gastrointestinal Surgery, Montreal General Hospital, McGill University Health Centre, Montreal, Quebec, Canada. FAU - Tlsty, Thea D AU - Tlsty TD AD - Department of Pathology, University of California, San Francisco, California, USA. FAU - Schilling, Birgit AU - Schilling B AUID- ORCID: 0000-0001-9907-2749 AD - Buck Institute for Research on Aging, Novato, California, USA. LA - eng GR - 27145/CRUK_/Cancer Research UK/United Kingdom GR - S10 OD016281/OD/NIH HHS/United States GR - A29071/CRUK_/Cancer Research UK/United Kingdom GR - A27145/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221013 PL - Germany TA - Proteomics JT - Proteomics JID - 101092707 RN - 0 (Extracellular Matrix Proteins) SB - IM MH - Humans MH - *Proteomics MH - Extracellular Matrix/metabolism MH - Lung/metabolism MH - *Carcinoma, Squamous Cell/pathology MH - Inflammation/metabolism MH - Extracellular Matrix Proteins/metabolism PMC - PMC10391693 MID - NIHMS1898790 OTO - NOTNLM OT - data-independent acquisition OT - extracellular matrix OT - lung squamous cell carcinoma OT - quantification OT - serpins COIS- The authors declare no conflict of interest. EDAT- 2022/10/14 06:00 MHDA- 2023/04/12 06:42 PMCR- 2024/03/03 CRDT- 2022/10/13 14:54 PHST- 2022/09/17 00:00 [revised] PHST- 2022/07/29 00:00 [received] PHST- 2022/09/21 00:00 [accepted] PHST- 2023/04/12 06:42 [medline] PHST- 2022/10/14 06:00 [pubmed] PHST- 2022/10/13 14:54 [entrez] PHST- 2024/03/03 00:00 [pmc-release] AID - PMIC13591 [pii] AID - 10.1002/pmic.202200021 [doi] PST - ppublish SO - Proteomics. 2023 Apr;23(7-8):e2200021. doi: 10.1002/pmic.202200021. Epub 2022 Oct 13.