Comprehensive analysis of tumor heterogeneity in neuroendocrine lung cancers
Csende Kristóf
KÁROLY RÁCZ CONSERVATIVE MEDICINE PROGRAM
Dr. Fekete Andrea
Országos Onkológiai Intézet, Előadóterem 3. épület fsz.
2025-10-21 13:40:00
Pulmonology
Dr. Losonczy György
Dr. Megyesfalvi Zsolt
Dr. Piros László
Dr. Buzás András
Dr. Zima Endre
Dr. Huszty Gergely Dénes
Dr. Dede Kristóf
Dr. Sótonyi Péter
Targeted therapy made a big leap in the treatment of cancerous diseases, but this option
needs more precise and advanced diagnosis. Despite being the deadliest subtype of lung
cancer, SCLC treatment lags behind that of other lung cancer types. Development of new
therapeutic agents needs a detailed landscape of SCLC molecular subtypes, both
concerning PTs and LN metastases. Our study profiled 32 surgically resected SCLCs and
corresponding LN metastases with RNASeq and IHC. The RNA expression profile
showed no differences between primary tumors and their paired LN metastases; however,
key differences emerged when the samples were examined by IHC. Specifically, DLL3
expression was significantly higher in the primary tumors than in corresponding LN
metastases, whereas NEUROD1 expression was significantly lower in the LN metastatic
lesions. A change in molecular subtype in the context of primary tumors – LN metastases
was seen in 21 cases. We continued with a broader investigation, analyzing the
immunologic profiles and expression patterns of LNENs. We identified several
immunomarkers that influenced survival. Elevated CD40 and CD137 expression was
associated with improved patient survival, while high CD47 and ICOS expression
correlated with worse patient outcomes. When we focused solely on the data of LCNEC
and SCLC, older age and vascular involvement was associated with significantly worse
survival. Further examination confirmed age as a key prognostic factor. According to
these findings, investigating LNENs requires a comprehensive clinical approach since
tumors from different sites show distinct phenotypes and immunologic landscapes that
can influence patient outcomes.
