Dissecting non-small cell lung cancer (NSCLC) with blood proteomics—from surgical to immunotherapeutic responses

Topic/Product:
Inflammation Panel 250, Oncology
Disease Area:
Cancer
Sample Type:
Plasma

Abstract

NSCLC remains a leading cause of cancer-related mortality, with limited biomarkers to guide surgical and immunotherapeutic intervention. This study leveraged two complementary plasma proteomics platforms, SomaScan (7596 proteins) and NULISA (250 inflammation-related proteins) to profile 87 timepoints from 56 NSCLC patients, collected pre- and post-surgery and pre- and post-ICI therapy. Robust biomarker selection used adaptive Lasso regression and the Stabl algorithm, with inter- and intra-cohort validation via orthogonal nELISA proteomics. Twenty-one differentially detectable plasma proteins were identified across treatment contexts. Surgical resection induced measurable proteomic changes: non-recurrent patients had higher circulating MUC16 and lower IL36G post-surgery, while recurrent patients showed elevated COX7A2L, FGF19, and SPOCK2, alongside lower FCER2, FCRLA, and SLITRK2. Among ICI-treated patients, responders had lower baseline levels of IL-6, CCL19, IL-2RA, CD200R1, CRP, LIF, PDCD1, CCL7, and SPP1, implicating systemic inflammation and immune regulation in treatment sensitivity. CEACAM5, PTX3, FGF23, and AREG were elevated in patients with worse clinical outcomes and poorer overall survival. MUC16, IL36G, CCL19, and IL-6 were independently validated by nELISA. Cross-platform comparison highlighted the complementary strengths of SomaScan’s broad proteomic coverage and NULISA’s sensitivity for low-abundance proteins. This integrated approach reveals distinct plasma signatures associated with surgical recurrence, ICI response, and prognosis in NSCLC.

Authors & Affiliations

Vahid Yaghoubi Naei¹˒²˒¹¹, Aaron Kilgallon²˒³˒¹¹, Gwendoline Mendes⁴, Akila Wijerathna-Yapa², Sanjay Dutta⁵, Clara Lawler², Connor O’Leary⁵, William Mullally⁵, James Monkman², James Mansfield⁶, Julien Hedou⁴˒⁷, Mark N. Adams⁸, Ken O’Byrne⁵˒⁸, Majid E. Warkiani⁹˒¹⁰, and Arutha Kulasinghe²˒³

¹ School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW, Australia
² Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, QLD, Australia
³ Queensland Spatial Biology Centre, Wesley Research Institute, The Wesley Hospital, Brisbane, QLD, Australia
⁴ SurgeCare SAS, Illkirch-Graffenstaden, France
⁵ The Princess Alexandra Hospital, Brisbane, QLD, Australia
⁶ Standard BioTools Canada Inc, Markham, ON, Canada
⁷ Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Paris, France
⁸ Queensland University of Technology, Brisbane, QLD, Australia
⁹ Department of Mechanical Engineering, College of Engineering, American University of Sharjah, Sharjah, United Arab Emirates
¹⁰ The Advanced Biosciences and Bioengineering Research Center, American University of Sharjah, Sharjah, United Arab Emirates
¹¹ These authors contributed equally: Vahid Yaghoubi Naei, Aaron Kilgallon.

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.