PhD Scientific Days 2025

Pathological and Oncological Sciences I.

Rapid research autopsy of SCLC patients: Insights into tumor heterogeneity

Előadó neve

Dr. Horváth Lilla

Neptun code

GK36R7

Előadó munkahelye

National Koranyi Institute of Pulmonology, Budapest

Előadó telefonszáma

+36307052974

Előadó e-mail címe

lilla.drhorvath@gmail.com

Az előadás címe

Rapid research autopsy of SCLC patients: Insights into tumor heterogeneity

Szerző(k) neve és munkahelye

Lilla Horvath¹, Zsolt Megyesfavi², Simon Heeke³, Jeovanis Gil Valdes⁴, Beata Szeitz⁵, Benjamin B. Morris³, Bence Ferencz⁶, Ildikó Kovács⁷, Vivien Teglas⁶, Janos Fillinger⁶, Maria Pozonec⁶, Szilvia Torok⁷, Eniko Tatrai⁷, Kristiina Boettiger⁸, Anna Solta⁸, Busra Ernhofer⁸, Krisztina Bogos⁷, Veronika Pozonec⁹, Marcos Malumbres¹⁰, Ferenc Renyi-Vamos¹¹, Clemens Aigner⁸, Karin Schelch⁸, Carl M. Gay³, Jianjun Zhang³, Lauren A. Byers³, Luis Paz-Ares¹², Peter Van Loo¹³, Gyorgy Marko-Varga⁴, John V. Heymach³, Balazs Dome¹⁴

1: 1-National Koranyi Institute of Pulmonology, Budapest
2: 1- National Koranyi Institute of Pulmonology, Budapest, 2-Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary;
3: Department of Thoracic/Head & Neck Medical Oncology, UT MD Anderson Cancer Center, Houston, Texas, USA
4: Department of Biomedical Engineering, Lund, Sweden
5: National Koranyi Institute of Pulmonology, Budapest,
6: National Koranyi Institute of Pulmonology, Budapest, 2-Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary
7: National Koranyi Institute of Pulmonology, Budapest
8: Hungary Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
9: Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary
10: Cancer Cell Cycle Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
11: National Koranyi Institute of Pulmonology, Budapest, 2-Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary;
12: Hospital Universitario 12 de Octubre, CNIO-H120 Lung Cancer Unit, Complutense University and Ciberonc, Madrid, Spain
13: Department of Genetics, UT MD Anderson Cancer Center, Houston, Texas, USA
14: 1- National Koranyi Institute of Pulmonology, Budapest, 2-Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; 3- Hungary Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria, Department of Translational Medicine, Lund University, Lund, Sweden

Bemutatás módja

Szóbeli

Szekció

Pathological and Oncological Sciences I.

Language of the presentation

English

Preferred session

Pathological and Oncological Sciences

Összefoglaló szövege

Background: Small cell lung cancer (SCLC) is a recalcitrant disease, and current therapies rarely provide long-term survival. To understand the complexity of SCLC, it is crucial to analyze primary and multiple metastatic lesions. Here, we investigated SCLC heterogeneity with regard to protein expression and molecular subtypes, and identify stably expressed therapeutic targets across distinct metastatic sites.
Method: Representative tumor and matched non-tumorous control samples were acquired via our multicenter SCLC rapid research autopsy (RRA) program (Megyesfalvi et al., Cancer Cell. 2023). Snap-frozen and formalin-fixed samples were subjected to RNAseq, proteomics analysis (nLC–MS/MS), and immunohistochemistry (IHC). We used bioinformatics to evaluate inter-site tumor heterogeneity and to select differentially/stably expressed molecules.
Results: We collected 194 tumor and 60 non-tumorous control specimens from various tumor sites in 23 SCLC patients. On average, 19354 transcripts and 7786 protein groups were quantified per sample. Clinically relevant SCLC-related proteins and therapeutic targets exhibited a moderate to high degree of inter-site heterogeneity. Specifically, ANXA1, TGFB1, STING1, and AURKA showed increased, while DLL3, BCL-2, SLFN11, SEZ6, B7-H3, and PARP displayed moderate inter-tumor heterogeneity, respectively. IHC confirmed the proteomics-derived results, revealing site-specific variability in DLL3 and B7-H3 levels. We identified 27 potential therapeutic targets showing tumor-specificity (p<0.001) and a low degree of inter-site variability in their expression pattern. Besides SCLC-A, -N, -AN, -P, and -QN, IHC defined a unique subtype with high ASCL1 expression and inflamed characteristics (SCLC-A-inflamed). Notably, significant subtype intra-tumoral heterogeneity was identified in 59% of the cases. In 85% of our patients, the dominant molecular subtype differed across metastatic sites, as per IHC.
Conclusions: Molecular subtypes show both intra-tumoral and inter-site variability. Several clinically relevant proteins and therapeutic targets have heterogeneous expression profiles across primary and metastatic SCLC lesions. The identified stably expressed emerging therapeutic targets could improve the effectiveness of treatments in SCLC.

Funding: none

University

Semmelweis University

Supervisor

Zsolt Megyesfalvi and Balazs Döme

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies before complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem hagyta jóvá

Előadó

8240

Start

15:45

End

16:00