2024/05/10 by Valentina Angerilli, Giovanna Sabella, Michele Simbolo +14 · 6 citations
Medicine · #Biology #Cancer #Cancer Immunotherapy and Biomarkers #Cancer research #Colorectal cancer #Gene #Gene expression #Genetics #Internal medicine #KRAS #MEN1 #Medicine #Multiple endocrine neoplasia #Neuroendocrine Tumor Research Advances #Neuroendocrine tumors #Pancreatic and Hepatic Oncology Research #Pancreatic cancer #Pathology #Transcriptome
paper · pdf · doi:10.1038/s41416-024-02705-8
openalex publication_date 2024/05/10 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Abstract Background High-grade gastro-entero-pancreatic neoplasms (HG GEP-NENs) can be stratified according to their morphology and Ki-67 values into three prognostic classes: neuroendocrine tumors grade 3 (NETs G3), neuroendocrine carcinomas with Ki-67 < 55% (NECs <55) and NECs with Ki-67 ≥ 55% (NECs ≥55). Methods We analyzed a cohort of 49 HG GEP-NENs by targeted Next-Generation Sequencing (TrueSight Oncology 500), RNA-seq, and immunohistochemistry for p53, Rb1, SSTR-2A, and PD-L1. Results Frequent genomic alterations affected TP53 (26%), APC (20%), KRAS and MEN1 (both 11%) genes. NET G3 were enriched in MEN1 ( p = 0.02) mutations, while both NECs groups were enriched in TP53 ( p = 0.001), APC ( p = 0.002) and KRAS ( p = 0.02) mutations and tumors with TMB ≥ 10 muts/Mb ( p = 0.01). No differentially expressed (DE) gene was found between NECs <55% and NECs ≥55%, while 1129 DE genes were identified between NET G3 and NECs. A slight enrichment of CD4 + and CD8 + T cells in NECs and of cancer-associated fibroblasts and macrophages (M2-like) in NET G3. Multivariate analysis identified histologic type and Rb1 loss as independent prognostic factors for overall survival. Conclusions This study showed that GEP-NET G3 and GEP-NECs exhibit clear genomic and transcriptomic differences, differently from GEP-NECs <55% and GEP-NECs ≥55%, and provided molecular findings with prognostic and potentially predictive value.