Tumor-educated platelet blood tests for Non-Small Cell Lung Cancer detection and management

Mafalda Antunes-Ferreira; Silvia D'Ambrosi; Mohammad Arkani; Edward Post; Sjors G J G In 't Veld; Jip Ramaker; Kenn Zwaan; Ece Demirel Kucukguzel; Laurine E Wedekind; Arjan W Griffioen; Mirjam Oude Egbrink; Marijke J E Kuijpers; Daan van den Broek; David P Noske; Koen J Hartemink; Siamack Sabrkhany; Idris Bahce; Nik Sol; Harm-Jan Bogaard; Danijela Koppers-Lalic; Myron G Best; Thomas Wurdinger

doi:10.1038/s41598-023-35818-w

Tumor-educated platelet blood tests for Non-Small Cell Lung Cancer detection and management

Sci Rep. 2023 Jun 8;13(1):9359. doi: 10.1038/s41598-023-35818-w.

Authors

Mafalda Antunes-Ferreira^#^{1

2

3}, Silvia D'Ambrosi^#^{1

2

3}, Mohammad Arkani^#^{1

2

4

5}, Edward Post^{1

2

3}, Sjors G J G In 't Veld^{1

2

3}, Jip Ramaker^{1

2

3}, Kenn Zwaan^{1

2

3}, Ece Demirel Kucukguzel^{1

2

3}, Laurine E Wedekind^{1

2

3}, Arjan W Griffioen^{2

6}, Mirjam Oude Egbrink⁷, Marijke J E Kuijpers⁸, Daan van den Broek⁹, David P Noske^{1

2

3}, Koen J Hartemink¹⁰, Siamack Sabrkhany⁷, Idris Bahce⁴, Nik Sol^{2

3

11}, Harm-Jan Bogaard⁴, Danijela Koppers-Lalic¹², Myron G Best^{1

2

3}, Thomas Wurdinger^{13

14

15}

Affiliations

¹ Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
² Cancer Center Amsterdam, Amsterdam, The Netherlands.
³ Brain Tumor Center Amsterdam, Amsterdam, The Netherlands.
⁴ Department of Pulmonary Medicine, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.
⁵ Department of Biomedical Data Science, Leiden University Medical Center, Leiden, The Netherlands.
⁶ Department of Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.
⁷ Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
⁸ Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
⁹ Department of Laboratory Medicine, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
¹⁰ Department of Thoracic Surgery, The Netherlands Cancer Institute-Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
¹¹ Department of Neurology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.
¹² Mathematical Institute, Leiden University, 2333, Leiden, CA, The Netherlands.
¹³ Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. t.wurdinger@gmail.com.
¹⁴ Cancer Center Amsterdam, Amsterdam, The Netherlands. t.wurdinger@gmail.com.
¹⁵ Brain Tumor Center Amsterdam, Amsterdam, The Netherlands. t.wurdinger@gmail.com.

^# Contributed equally.

Abstract

Liquid biopsy approaches offer a promising technology for early and minimally invasive cancer detection. Tumor-educated platelets (TEPs) have emerged as a promising liquid biopsy biosource for the detection of various cancer types. In this study, we processed and analyzed the TEPs collected from 466 Non-small Cell Lung Carcinoma (NSCLC) patients and 410 asymptomatic individuals (controls) using the previously established thromboSeq protocol. We developed a novel particle-swarm optimization machine learning algorithm which enabled the selection of an 881 RNA biomarker panel (AUC 0.88). Herein we propose and validate in an independent cohort of samples (n = 558) two approaches for blood samples testing: one with high sensitivity (95% NSCLC detected) and another with high specificity (94% controls detected). Our data explain how TEP-derived spliced RNAs may serve as a biomarker for minimally-invasive clinical blood tests, complement existing imaging tests, and assist the detection and management of lung cancer patients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Biomarkers, Tumor / genetics
Blood Platelets / metabolism
Carcinoma, Non-Small-Cell Lung* / genetics
Hematologic Tests
Humans
Lung Neoplasms* / genetics
RNA / metabolism

Substances

Biomarkers, Tumor
RNA