Identification of protein biomarkers for prediction of response to platinum-based treatment regimens in patients with non-small cell lung cancer

Franziska Bottger, Teodora Radonic, Idris Bahce, Kim Monkhorst, Sander R. Piersma, Thang V. Pham, Anne-Marie C. Dingemans, Lisa M. Hillen, Mariacarmela Santarpia, Elisa Giovannetti, Egbert F. Smit, Sjaak A. Burgers, Connie R. Jimenez*

*Corresponding author for this work

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Abstract

The majority of patients with resected stage II-IIIA non-small cell lung cancer (NSCLC) are treated with platinum-based adjuvant chemotherapy (ACT) in a one-size-fits-all approach. However, a significant number of patients do not derive clinical benefit, and no predictive patient selection biomarker is currently available. Using mass spectrometry-based proteomics, we have profiled tumour resection material of 2 independent, multi-centre cohorts of in total 67 patients with NSCLC who underwent ACT. Unsupervised cluster analysis of both cohorts revealed a poor response/survival sub-cluster composed of ~ 25% of the patients, that displayed a strong epithelial-mesenchymal transition signature and stromal phenotype. Beyond this stromal sub-population, we identified and validated platinum response prediction biomarker candidates involved in pathways relevant to the mechanism of action of platinum drugs, such as DNA damage repair, as well as less anticipated processes such as those related to the regulation of actin cytoskeleton. Integration with pre-clinical proteomics data supported a role for several of these candidate proteins in platinum response prediction. Validation of one of the candidates (HMGB1) in a third independent patient cohort using immunohistochemistry highlights the potential of translating these proteomics results to clinical practice.

Original languageEnglish
Number of pages20
JournalMolecular Oncology
Early online date27 Nov 2023
DOIs
Publication statusE-pub ahead of print - 27 Nov 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

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