WCLC 2025 - Posters & ePosters-P2.06.93 Distinct Clinical and Biological Features of Five SCLC Subtypes Identified by Plasma Proteomic Analysis

Pdf Summary

This study investigates small cell lung cancer (SCLC) subtyping through plasma proteomic profiling, aiming to overcome limitations of current biopsy-based methods such as intratumoral heterogeneity and invasiveness. SCLC is a biologically heterogeneous disease traditionally classified into four molecular subtypes (SCLC-A, SCLC-N, SCLC-P, SCLC-I) based on tumor biopsy molecular profiles. The study analyzed pretreatment plasma from 79 patients with extensive-stage SCLC undergoing immune checkpoint inhibitor and chemotherapy treatment. Using an aptamer-based assay quantifying ~7000 proteins per sample and consensus clustering, five distinct SCLC subtypes were identified from plasma proteomic patterns.<br /><br />One subtype, termed subtype-3, showed a proteomic signature rich in neuroendocrine biomarkers associated with the neuroendocrine-high SCLC-A subtype. This group had significantly poorer overall survival (median OS 6.02 months) compared to other subtypes (median OS ranged 9.9-14.6 months), and was enriched with poor prognostic factors such as high ECOG performance status. Subtypes 1, 2, and 5 demonstrated higher expression of NOTCH pathway proteins linked to non-neuroendocrine features and better clinical outcomes. An analysis using a plasma proteomics-based biological age predictor revealed subtype-3 patients had the greatest discrepancy between biological and chronological age, correlating with their worse prognosis.<br /><br />The plasma proteomic approach offers advantages including minimal invasiveness, circumvention of tumor heterogeneity constraints, and feasibility of serial monitoring to detect dynamic subtype switching during therapy. The proteomic data highlighted 469 differentially expressed proteins clustered into groups with distinct biological functions, reinforcing the molecular heterogeneity of SCLC. Ongoing research aims to elucidate therapeutic vulnerabilities specific to these newly defined plasma proteomic subtypes and to discover novel treatment targets. This study demonstrates that plasma proteomic profiling can serve as a practical, prognostically meaningful tool for SCLC subtyping to guide personalized treatment strategies.

Asset Subtitle

David Gandara

Meta Tag

Speaker David Gandara

Topic Pathology and Biomarkers

Keywords

small cell lung cancer

SCLC subtyping

plasma proteomic profiling

immune checkpoint inhibitor

neuroendocrine biomarkers

NOTCH pathway proteins

overall survival

biological age predictor

tumor heterogeneity

personalized treatment