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Quantitative proteomics identifies brain acid soluble protein 1 (BASP1) as a prognostic biomarker candidate in pancreatic cancer tissue

Zhou, Qimin LU orcid ; Andersson, Roland LU ; Hu, Dingyuan LU ; Bauden, Monika LU orcid ; Kristl, Theresa LU ; Sasor, Agata LU ; Pawłowski, Krzysztof LU ; Pla, Indira LU orcid ; Hilmersson, Katarzyna Said LU and Zhou, Mengtao , et al. (2019) In EBioMedicine 43. p.282-294
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
BASP1, Biomarkers, Chemotherapy response, Mass spectrometry, Pancreatic cancer, Prognosis, WT1
in
EBioMedicine
volume
43
pages
13 pages
publisher
Elsevier
external identifiers
  • scopus:85064170997
  • pmid:30982764
ISSN
2352-3964
DOI
10.1016/j.ebiom.2019.04.008
language
English
LU publication?
yes
id
e2385854-3521-4f52-bc71-4f3e420bb1c1
alternative location
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064170997&doi=10.1016%2fj.ebiom.2019.04.008&partnerID=40&md5=70dc2d4ca02fd23fde6d9ea366d4832b
date added to LUP
2019-04-25 13:42:18
date last changed
2024-05-28 08:16:32
@article{e2385854-3521-4f52-bc71-4f3e420bb1c1,
  abstract     = {{<p>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.</p>}},
  author       = {{Zhou, Qimin and Andersson, Roland and Hu, Dingyuan and Bauden, Monika and Kristl, Theresa and Sasor, Agata and Pawłowski, Krzysztof and Pla, Indira and Hilmersson, Katarzyna Said and Zhou, Mengtao and Lu, Fan and Marko-Varga, György and Ansari, Daniel}},
  issn         = {{2352-3964}},
  keywords     = {{BASP1; Biomarkers; Chemotherapy response; Mass spectrometry; Pancreatic cancer; Prognosis; WT1}},
  language     = {{eng}},
  pages        = {{282--294}},
  publisher    = {{Elsevier}},
  series       = {{EBioMedicine}},
  title        = {{Quantitative proteomics identifies brain acid soluble protein 1 (BASP1) as a prognostic biomarker candidate in pancreatic cancer tissue}},
  url          = {{http://dx.doi.org/10.1016/j.ebiom.2019.04.008}},
  doi          = {{10.1016/j.ebiom.2019.04.008}},
  volume       = {{43}},
  year         = {{2019}},
}