Abstract 1241P
Background
Non-small cell lung cancer (NSCLC) stands as a prevailing cause of cancer-related death worldwide, largely due to the late-stage diagnosis that diminishes the prospects of cure. Abnormal protein glycosylation, a recognized hallmark of cancer, offers a promising avenue for the exploration of novel biomarkers. Recent advancements in AI-supported analytical technologies have opened possibilities for a thorough examination of cancer-specific glycoforms. The objective of this study is to identify circulating glycoproteomic biomarkers for the early detection of NSCLC, with the potential to enhance patient outcomes and revolutionize diagnostic approaches.
Methods
With a novel high resolution and high throughput glycoproteomic profiling platform combining liquid-chromatography/mass-spectrometry (LC-MS) and artificial-intelligence (AI)-powered data processing, we assessed 694 glycopeptide (GP) and non-glycosylated peptide quantification transitions in pre-treatment peripheral blood serum samples from 372 NSCLC, 148 COPD, and 494 healthy individuals. The full sample set was split into training and validation loops, with a held-out test set. Cross-validated elastic net-regularized logistic regression was performed to develop a multivariate classifier to detect NSCLC.
Results
A total of 340 statistically significantly (FDR < 0.05) differentially abundant glycopeptides (GPs)/peptides when comparing NSCLC and healthy controls, and 50 biomarkers were significantly differentially expressed between healthy controls and NSCLC samples, COPD and NSCLC samples, but not between healthy controls and COPD samples. A multivariate model achieved 85.5% specificity and 84.2% sensitivity to detect all stages of NSCLC with an AUC of 0.875 in a held-out test set. Notably, it performed well in detecting both early (stages I-II) and late stages of NSCLC (stages III-IV) with sensitivities of 81.8% and 87.2%, respectively.
Conclusions
We established a novel platform combining LC-MS and AI data processing, and identified comprehensive serum glycoproteomic profiles which allow the further clinical translations including development of effective non-invasive NSCLC screening and early detection tools.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
InterVenn Biosciences.
Funding
InterVenn Biosciences.
Disclosure
K. He: Financial Interests, Personal, Advisory Board: Mirati, Iovance, BMS, AstraZeneca, Lyell, BeiGene; Financial Interests, Personal and Institutional, Coordinating PI: mirati, OncoC4; Financial Interests, Personal and Institutional, Steering Committee Member: Iovance, Lyell; Financial Interests, Personal and Institutional, Local PI: BMS; Financial Interests, Personal, Steering Committee Member: BeiGene; Financial Interests, Institutional, Local PI: Amgen, GSK, Genentech. G. Absenger: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Takeda, Sanofi, Roche. C. Pickering, C. Guerrier, C. Dhar, G. Xu, J. Hartness, R. Rice, F. Schwarz, D. Serie, D. Hommes: Financial Interests, Personal, Full or part-time Employment: InterVenn. L. Brcic: Financial Interests, Personal, Advisory Board: Invitae, Eli Lilly, AstraZeneca, Bristol Myers Squibb, Janssen, Lilly, Merck, Novartis, Pfizer, Takeda, MSD, Roche.
Resources from the same session
1251P - Development of a deep learning algorithm for lung cancer diagnosis using methylation and fragment size profiles of cfDNA
Presenter: Jiyoung Huh
Session: Poster session 14
1252P - Quantitative cell signaling activity profiling of solid tumors to support personalized treatment in the FINPROVE basket trial: Presentation of skin tumor data
Presenter: Diederick Keizer
Session: Poster session 14
1253P - Analytic validation and implementation of OncoDEEP: A pan-cancer comprehensive genomic profiling NGS assay for assessing homologous recombination deficiency (HRD)
Presenter: Marcel Trautmann
Session: Poster session 14
1254P - Retrospective analysis of brain OMX: Diagnostic tool for structural (T1) and functional connectome (RS-FMRI) analysis of brain
Presenter: Swarnambiga Ayyachamy
Session: Poster session 14
1255P - Evaluating GPT-4 as an academic support tool for clinicians: A comparative analysis of case records from the literature
Presenter: Marcos Aurelio Fonseca Magalhaes Filho
Session: Poster session 14
1256P - Value of detection of peripheral blood circRNA based on digital PCR in the diagnosis of lung adenocarcinoma
Presenter: Jihong Zhou
Session: Poster session 14
1257P - Double heterozygous prevalence in hereditary cancer syndromes in Northern Mexico population
Presenter: Carlos Burciaga Flores
Session: Poster session 14
1258P - Does FDG PET-based radiomics have an added value for prediction of overall survival in non-small cell lung cancer?
Presenter: Andrea Ciarmiello
Session: Poster session 14
1260TiP - Enhancing lung nodule discrimination with a novel cfDNA test: The cancer signature ensemble (CSE) approach
Presenter: Young-Chul Kim
Session: Poster session 14
1773P - ICECaP-2: Validation of metastasis-free survival (MFS) as a surrogate for overall survival (OS) in localized prostate cancer (LPC) in a more contemporary era
Presenter: Wanling Xie
Session: Poster session 14