Dr. Megyesfalvi Zsolt 1,2,3
1 Department of Tumor Biology, National Korányi Institute of Pulmonology, Budapest, Hungary
2 Department of Thoracic Surgery, National Institute of Oncology, Budapest, Hungary
Introduction: Recent preclinical cell line data suggest that neuroendocrine (NE) pattern of small cell lung cancer (SCLC) has strong therapeutic relevance. NE high tumors are associated with immune desert and NE low tumors are considered immune oasis phenotype.
Aims: The aim of our study was to confirm the preclinical data in the clinical setting and further investigate the NE features of SCLC according to inter-tumor heterogeneity.
Method: Targeted RNA-sequencing of 2560 genes was performed on 32 matched surgically resected SCLC patients primary tumors and lymph node (LN) metastases. We performed a cluster analysis and heat map to divide patients into NE high and NE low subtypes by using the top NE associated genes described in preclinical studies. Statistical analyses were performed by Student’s t-test and Mann-Whitney U test.
Results: Cluster analysis clearly identified SCLC NE subtypes according to primary tumor (NE high vs. low, 20 vs. 12, respectively) and LNs (NE high vs. low, 23 vs. 9, respectively). In case of five patients, a change in NE pattern was observed, suggesting a possible inter-tumor heterogeneity regarding NE differentiation. Moreover, a significant downregulation of NE associated genes CAV1, CAV2 and ANXA3 was found in LN metastases compared to primary tumor. A lower expression of NE associated key RNA genes REST and Myc, and the higher expression of DLL3 in NE high subtype are in accordance with the preclinical findings and confirms the accuracy of the cluster analysis performed.
Conclusion: Our data confirm the results of preclinical studies and show NE low and high differentiation clusters in SCLC. NE pattern of the LN metastatic lesions might not reflect the NE phenotype of the primary tumor, consequently, treatment decisions including immunotherapy administration needs to be further investigated in this setting.
Doctoral School: Clinical Medicine
Supervisors: Balázs Döme, Zoltán Lohinai
E-mail address: email@example.com