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

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Quantitative proteomics identifies brain acid soluble protein 1 (BASP1) as a prognostic biomarker candidate in pancreatic cancer tissue. / Zhou, Qimin; Andersson, Roland; Hu, Dingyuan; Bauden, Monika; Kristl, Theresa; Sasor, Agata; Pawłowski, Krzysztof; Pla, Indira; Hilmersson, Katarzyna Said; Zhou, Mengtao; Lu, Fan; Marko-Varga, György; Ansari, Daniel.

In: EBioMedicine, Vol. 43, 2019, p. 282-294.

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T1 - Quantitative proteomics identifies brain acid soluble protein 1 (BASP1) as a prognostic biomarker candidate in pancreatic cancer tissue

AU - Zhou, Qimin

AU - Andersson, Roland

AU - Hu, Dingyuan

AU - Bauden, Monika

AU - Kristl, Theresa

AU - Sasor, Agata

AU - Pawłowski, Krzysztof

AU - Pla, Indira

AU - Hilmersson, Katarzyna Said

AU - Zhou, Mengtao

AU - Lu, Fan

AU - Marko-Varga, György

AU - Ansari, Daniel

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - BASP1

KW - Biomarkers

KW - Chemotherapy response

KW - Mass spectrometry

KW - Pancreatic cancer

KW - Prognosis

KW - WT1

U2 - 10.1016/j.ebiom.2019.04.008

DO - 10.1016/j.ebiom.2019.04.008

M3 - Article

VL - 43

SP - 282

EP - 294

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -