PhD Scientific Days 2020

Pathology and Oncology I. Lectures

Molecular Subtypes of Small Cell Lung Cancer: Proteomic Characterization and Potential Clinical Implications

Előadó neve

Dr. Megyesfalvi, Zsolt

Előadó munkahelye

Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest

Előadó telefonszáma

+36204243934

Előadó e-mail címe

megyesfalvi.zsolt@semmelweis-univ.hu

Az előadás címe

Molecular Subtypes of Small Cell Lung Cancer: Proteomic Characterization and Potential Clinical Implications

Szerző(k) neve és munkahelye

Zsolt Megyesfalvi1,2,3; Nándor Bárány2,3; Zsuzsanna Valkó3; Sándor Paku4; Edina Bugyik4; Melinda Rezeli5; Beata Szeitz5; Nicole Woldmar5; Judit Moldvay2,6; Ferenc Rényi-Vámos7; György Markó-Varga5; Viktória László2,3; Balázs Döme1,2,3

1- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary
2- Department of Tumor Biology, National Korányi Institute of Pulmonology, Budapest, Hungary
3- Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Austria
4- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
5- Center of Excellence in Biological and Medical Mass Spectrometry, Biomedical Center, Lund University, Lund, Sweden
6- 1st Department of Pulmonology, National Korányi Institute of Pulmonology, Budapest, Hungary
7- Department of Thoracic Surgery, National Korányi Institute of Pulmonology, Budapest, Hungary

Szekció

Pathology and Oncology I. Lectures

Language of the presentation

English

Section, first choice

Pathology and Oncology

Section, second choice

Clinical Medicine

Összefoglaló szövege

Introduction: Until recently, small cell lung cancer (SCLC) was defined as a homogenous entity and thus SCLC patients have been treated similarly with no relevant changes in the standard of care chemotherapy for over three decades. Nevertheless, recent results suggest that there are significant differences within the SCLC category with regards to the expression of four different lineage-specific transcription regulators.

Aims: Our aim was to investigate the four molecular subtypes of SCLC at the proteome level and to explore their clinical relevance.

Method: In total, 19 SCLC cell lines were subjected to in-depth proteomic analysis, qPCR and Western Blot techniques. We investigated the mechanisms and molecular background underlying the differences between subtypes utilizing integrative bioinformatic analyses. In order to investigate the clinicopathological relevance of the molecular subtypes, immunohistochemical analyses will be performed on 153 surgically resected SCLC tissue specimens.

Results: Comprehensively, 9228 proteins were quantified in the 19 SCLC cell lines (>8000 proteins per sample). Unsupervised hierarchical cluster analysis of the protein expression levels clearly distinguished the SCLC molecular subtypes of the cell lines. The results of the cluster analyses were confirmed by qPCR and Western Blot techniques. In regard to the protein expression heterogeneity between different subtypes, a significant difference was found in case of 1650 proteins [17% (p<0.001)]. Furthermore, we identified 126 unique proteins, that were expressed only in one particular subtype. The immunohistochemical classification of the surgically resected tumor tissue specimens are in progress and will be presented at the conference.

Conclusion: This study is the first differentiating SCLC molecular subtypes based on in-depth proteomic analysis. Accordingly, our results might help to gain a deeper understanding of the oncogenesis of SCLC, the resistance mechanisms and, moreover, to identify markers that may guide treatment decisions with regard to the molecular subtypes.

Additional Information

Supervisor: Balázs Döme
E-mail address: balazs.dome@meduniwien.ac.at.

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4071

Start

10:50

End

11:05

Authors (legacy)

Zsolt Megyesfalvi1,2,3; Nándor Bárány2,3; Zsuzsanna Valkó3; Sándor Paku4; Edina Bugyik4; Melinda Rezeli5; Beata Szeitz5; Nicole Woldmar5; Judit Moldvay2,6; Ferenc Rényi-Vámos7; György Markó-Varga5; Viktória László2,3; Balázs Döme1,2,3

1- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary
2- Department of Tumor Biology, National Korányi Institute of Pulmonology, Budapest, Hungary
3- Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Austria
4- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
5- Center of Excellence in Biological and Medical Mass Spectrometry, Biomedical Center, Lund University, Lund, Sweden
6- 1st Department of Pulmonology, National Korányi Institute of Pulmonology, Budapest, Hungary
7- Department of Thoracic Surgery, National Korányi Institute of Pulmonology, Budapest, Hungary