Multiplex immune protein profiling of fine-needle aspirates from patients with non-small-cell lung cancer reveals signatures associated with PD-L1 expression and tumor stage.

Abstract

Biomarker signatures identified through minimally invasive procedures already at diagnosis of non-small-cell lung cancer (NSCLC) could help to guide treatment with immune checkpoint inhibitors (ICI). Here, we performed multiplex profiling of immune-related proteins in fine-needle aspirate (FNA) samples of thoracic lesions from patients with NSCLC to assess PD-L1 expression and identify related protein signatures. Transthoracic FNA samples from 14 patients were subjected to multiplex antibody-based profiling by proximity extension assay (PEA). PEA profiling employed protein panels relevant to immune and tumor signaling and was followed by Qlucore® Omics Explorer analysis. All lesions analyzed were NSCLC adenocarcinomas, and PEA profiles could be used to monitor 163 proteins in all but one sample. Multiple key immune signaling components (including CD73, granzyme A, and chemokines CCL3 and CCL23) were identified and expression of several of these proteins (e.g., CCL3 and CCL23) correlated to PD-L1 expression. We also found EphA2, a marker previously linked to inferior NSCLC prognosis, to correlate to PD-L1 expression. Our identified protein signatures related to stage included, among others, CXCL10 and IL12RB1. We conclude that transthoracic FNA allows for extensive immune and tumor protein profiling with assessment of putative biomarkers of important for ICI treatment selection in NSCLC.

• Authors: Bo Franzén, Kristina Viktorsson, Caroline Kamali, Eva Darai-Ramqvist, Vitali Grozman, Vasiliki Arapi, Petra Hååg, Vitaliy O Kaminskyy, Per Hydbring, Lena Kanter, Sven Nyrén, Simon Ekman, Luigi De Petris, Rolf Lewensohn
• Journal: Molecular oncology (Mol Oncol) Vol. 15 Issue 11 Pg. 2941-2957 (11 2021) ISSN: 1878-0261 [Electronic] United States
• PMID: 33768639 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Chemical References

• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human

Topics

• Adenocarcinoma
• B7-H1 Antigen (metabolism)
• Biomarkers, Tumor (metabolism)
• Biopsy, Fine-Needle
• Carcinoma, Non-Small-Cell Lung (pathology)
• Humans
• Lung Neoplasms (pathology)