Characterization of Pulmonary Neuroendocrine Tumors

Project 1: Spatial Transcriptomic Characterization of Rare Pulmonary Neuroendocrine Tumors

Project Summary

This project aims to precisely characterize rare pulmonary neuroendocrine tumors through innovative spatial transcriptomics technology (Xenium – 10X Genomics), focusing specifically on mixed small cell (SCLC) and large cell (LCNEC) neuroendocrine lung carcinomas.

Context and Challenges

Mixed SCLC-LCNEC carcinomas are rare forms (<1% of lung cancers) marked by high morphological and molecular heterogeneity. The very poor prognosis (<1 year median survival) necessitates a deeper molecular and spatial understanding to optimize diagnosis, prognosis, and therapeutic guidance.

Project Objectives

Describe the spatial molecular heterogeneity of mixed SCLC-LCNEC carcinomas.
Identify transcriptomic profiles and key biomarkers of these rare tumors.
Determine molecular similarities and differences between SCLC and LCNEC components within these mixed tumors.

Methodology

Execution of spatial transcriptomics (Xenium, 10X Genomics) to characterize in situ gene expression at the cellular level. in situ au niveau cellulaire.
In-depth bioinformatic analysis to identify markers of interest and specific molecular pathways for different phenotypes.

Expected Results

Precise gene expression mapping of mixed SCLC-LCNEC carcinomas.
Identification of specific markers useful for improving diagnosis.
Enhanced understanding of molecular transition processes between different types of neuroendocrine tumors.

Involved Institutions and IHU WP

IPMC (Institute of Molecular and Cellular Pharmacology) – WP1
Nice University Hospital (LPCE – Clinical and Experimental Pathology Laboratory) – WP3

Project 2: Prevalence and Prognostic Value of the DLL3 Biomarker in Small Cell Lung Cancer

Project Summary

This project aims to accurately determine the prevalence and prognostic value of the DLL3 biomarker in small cell lung cancer (SCLC) and evaluate its correlation with different SCLC molecular subtypes to optimize targeted therapeutic strategies.

Context and Challenges

Small cell lung cancer (SCLC) remains an aggressive disease with few effective treatment options upon relapse. DLL3, an emerging biomarker linked to the Notch pathway, could be a promising target. However, its exact prevalence and prognostic value in a real-world clinical context remain poorly defined.

Project Objectives

Evaluate the precise prevalence of DLL3 expression at various tumor expression thresholds and staining intensities via immunohistochemistry.
Analyze the prognostic value of DLL3 on the actual overall survival of SCLC patients.
Correlate DLL3 expression with SCLC molecular subtypes (ASCL1, NEUROD1, POU2F3, YAP1).

Methodology

Retrospective analysis of tumor samples from patients diagnosed between 2017 and 2022.
Standardized automated immunohistochemistry.
Clinical and molecular correlation with SCLC subtypes, treatments received, and real-world patient survival data.real-world data).

Expected Results

Precise definition of clinically relevant DLL3 thresholds for therapeutic indication.
Validation of DLL3 as a reliable prognostic marker.
Direct contribution to the guidance of innovative treatments targeting DLL3 (bispecific antibodies, immunotherapy).

Involved Institutions and IHU WP

Nice University Hospital (LPCE – Clinical and Experimental Pathology Laboratory, Côte d’Azur Biobank) – WP1
Collaboration with Amgen USA.