PhD Scientific Days 2024
Budapest, 9-10 July 2024
Pathological and Oncological Sciences III.
Assessment of Small Cell Lung Cancer Tumor Heterogeneity Across Metastatic Sites by Multiomic Approaches
Előadó neve
Dr. Téglás, Vivien
Neptun code
E73O2O
Előadó munkahelye
Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; National Koranyi Institute of Pulmonology, Budapest, Hungary.
Előadó telefonszáma
209535885
Előadó e-mail címe
teglas.vivien@stud.semmelweis.hu
Az előadás címe
Assessment of Small Cell Lung Cancer Tumor Heterogeneity Across Metastatic Sites by Multiomic Approaches
Szerző(k) neve és munkahelye
Vivien Téglás1,2, Maria Dorothea Požonec1,2, Simon Heeke3, Beáta Szeitz2, Lilla Horváth2, Ben B. Morris3, Bence Ferencz1,2, Ildikó Kovács2, Janos Fillinger2, Anna Solta4, Kristiina Boettiger4, Busra Ernhofer4, Krisztina Bogos2, Clemens Aigner4, Karin Schelch4,5, Jeovanis Gil Valdés6, Kyle Concannon3, Monique B. Nilsson3, Carl M Gay3, Jianjun Zhang3, Lauren Byers3, Peter Van Loo7, Gyorgy Marko-Varga6, John V. Heymach3, Balazs Dome1,2,4,6, Zsolt Megyesfalvi1,2,4
1: Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary.
2: National Koranyi Institute of Pulmonology, Budapest, Hungary.
3: Department of Thoracic/Head & Neck Medical Oncology, UT MD Anderson Cancer Center, Houston, Texas, USA.
4: Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
5: Center for Cancer Research, Medical University of Vienna, Vienna, Austria.
6: Department of Translational Medicine, Lund University, Lund, Sweden.
7: Department of Genetics, UT MD Anderson Cancer Center, Houston, Texas, USA.
Bemutatás módja
Szóbeli
Szekció
Pathological and Oncological Sciences III.
Language of the presentation
English
Preferred session
Pathological and Oncological Sciences
Összefoglaló szövege
Introduction: Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. During disease progression, the initial increased clinical response rates are usually followed by the development of therapy resistance due to the tumoral heterogeneity in SCLC.
Aims: Our aim was to assess the degree of inter-site tumor heterogeneity in SCLC using multisite tissue samples obtained from rapid research autopsies (RRA).
Methods: In total, 7 patients with SCLC were subjected to RRA. Given that protein degradation starts almost immediately after circulatory arrest, the autopsy was carried out within four hours of the patient’s death, according to the Ghon technique. The tissue samples were preserved by snap-freezing and formalin fixation. We analyzed 66 specimens deriving from the primary tumors and different metastatic sites. MS-based proteomic analyses, RNAseq, and immunohistochemical stainings were performed to investigate intratumoral heterogeneity.
Results: More than 19000 transcripts and 7700 proteins were quantified by multiomic analyses. The correlation between the RNAseq and the proteomic data was modest (R=0.29). Furthermore, we identified 116 potentially druggable proteins, that showed constant expression in multisite tissue samples. Regarding molecular targets that are currently under clinical investigation, including BCL-2, DLL3, and SLFN11 we observed increased heterogeneity between different samples. Further detailed results will be presented during the conference.
Conclusion: Considering that we identified 116 targetable proteins that showed stable expression across primary tumors and different metastatic sites the intratumoral heterogeneity in SCLC was not as significant as we initially expected. The evaluation of human samples obtained via RRA offers unique insight into intratumoral heterogeneity and might pave the way for future biomarker-driven clinical trials in SCLC.
Funding: BD and ZM: Hungarian National Research, Development and Innovation Office (2020‐1.1.6‐JÖVŐ, TKP2021‐EGA‐33, FK‐14375, FK-147045)
ZM: New National Excellence Program of the Ministry for Innovation and Technology of Hungary (UNKP‐20‐3, UNKP‐21‐3, UNKP-23-5), Bolyai Research Scholarship of the Hungarian Academy of Sciences, International Association for the Study of Lung Cancer/International Lung Cancer Foundation Young Investigator Grant (2022)
University
Semmelweis University
Supervisor
Zsolt Megyesfalvi
Publication of my abstract
I do not give consent to the publication of my abstract on the website of the congress.
Kind
Szabad
Status
elfogadva
Accepted presentation method
szóbeli
Előadás fájl jóváhagyás
nem rendelkezett róla
Előadó
7986
Start
10:00
End
10:10