@article{5a9f361938b741d78700de8990583d8c,
title = "Quantitative proteomics identifies brain acid soluble protein 1 (BASP1) as a prognostic biomarker candidate in pancreatic cancer tissue",
abstract = "Background: Pancreatic cancer is a heterogenous disease with a poor prognosis. This study aimed to discover and validate prognostic tissue biomarkers in pancreatic cancer using a mass spectrometry (MS) based proteomics approach. Methods: Global protein sequencing of fresh frozen pancreatic cancer and healthy pancreas tissue samples was conducted by MS to discover potential protein biomarkers. Selected candidate proteins were further verified by targeted proteomics using parallel reaction monitoring (PRM). The expression of biomarker candidates was validated by immunohistochemistry in a large tissue microarray (TMA) cohort of 141 patients with resectable pancreatic cancer. Kaplan-Meier and Cox proportional hazard modelling was used to investigate the prognostic utility of candidate protein markers. Findings: In the initial MS-discovery phase, 165 proteins were identified as potential biomarkers. In the subsequent MS-verification phase, a panel of 45 candidate proteins was verified by the development of a PRM assay. Brain acid soluble protein 1 (BASP1) was identified as a new biomarker candidate for pancreatic cancer possessing largely unknown biological and clinical functions and was selected for further analysis. Importantly, bioinformatic analysis indicated that BASP1 interacts with Wilms tumour protein (WT1) in pancreatic cancer. TMA-based immunohistochemistry analysis showed that BASP1 was an independent predictor of prolonged survival (HR 0.468, 95% CI 0.257–0.852, p = .013) and predicted favourable response to adjuvant chemotherapy, whereas WT1 indicated a worsened survival (HR 1.636, 95% CI 1.083–2.473, p = .019) and resistance to chemotherapy. Interaction analysis showed that patients with negative BASP1 and high WT1 expression had the poorest outcome (HR 3.536, 95% CI 1.336–9.362, p = .011). Interpretation: We here describe an MS-based proteomics platform for developing biomarkers for pancreatic cancer. Bioinformatic analysis and clinical data from our study suggest that BASP1 and its putative interaction partner WT1 can be used as biomarkers for predicting outcomes in pancreatic cancer patients.",
keywords = "BASP1, Biomarkers, Chemotherapy response, Mass spectrometry, Pancreatic cancer, Prognosis, WT1",
author = "Qimin Zhou and Roland Andersson and Dingyuan Hu and Monika Bauden and Theresa Kristl and Agata Sasor and Krzysztof Paw{\l}owski and Indira Pla and Hilmersson, {Katarzyna Said} and Mengtao Zhou and Fan Lu and Gy{\"o}rgy Marko-Varga and Daniel Ansari",
note = "Funding Information: This work was supported by the Magnus Bergvall Foundation ( 2017-02189 ), the Inga and John Hain Foundation for Medical Research ( 2016-09-07/DA , 2017-09-07/DA ), the Clas Groschinsky Foundation ( M1741 , M18207 ), the Gunnar Nilsson Foundation ( GN-2018-1-90 ), the Gyllenstiernska Krapperup Foundation ( 2017-0055 ), the Erik and Angelica Sparre Research Foundation ( 2016-11-09/DA , 2018-10-28/DA ), the Emil and Wera Cornell Foundation ( 2018-06-18/DA ), the Crafoord Foundation ( 20170555 ), Governmental Funding of Clinical Research within the National Health Service ( ALF, 2018-YF0012 ) and Sweden's Innovation Agency (Vinnova, 2019-00715 ). The funding sources had no role in the design and conduct of this study; the analysis and interpretation of data; or the preparation and submission of the manuscript. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Funding Information: This work was supported by the Magnus Bergvall Foundation (2017-02189), the Inga and John Hain Foundation for Medical Research (2016-09-07/DA, 2017-09-07/DA), the Clas Groschinsky Foundation (M1741, M18207), the Gunnar Nilsson Foundation (GN-2018-1-90), the Gyllenstiernska Krapperup Foundation (2017-0055), the Erik and Angelica Sparre Research Foundation (2016-11-09/DA, 2018-10-28/DA), the Emil and Wera Cornell Foundation (2018-06-18/DA), the Crafoord Foundation (20170555), Governmental Funding of Clinical Research within the National Health Service (ALF, 2018-YF0012) and Sweden's Innovation Agency (Vinnova, 2019-00715). The funding sources had no role in the design and conduct of this study; the analysis and interpretation of data; or the preparation and submission of the manuscript. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. We thank Aniel Sanchez Puente, Jeovanis Gil Valdes, Lazaro Hiram Betancourt, and Melinda Rezeli for technical support. Thermo Fisher Scientific, San Jose, is greatly acknowledged for their generous support. Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = may,
doi = "10.1016/j.ebiom.2019.04.008",
language = "English (US)",
volume = "43",
pages = "282--294",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",
}