PMID- 37086484
OWN - NLM
STAT- MEDLINE
DCOM- 20230911
LR  - 20231010
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 28
IP  - 9
DP  - 2023 Sep 7
TI  - The Mutational, Prognostic, and Therapeutic Landscape of Neuroendocrine 
      Neoplasms.
PG  - e723-e736
LID - 10.1093/oncolo/oyad093 [doi]
AB  - BACKGROUND: Neuroendocrine neoplasms (NENs) represent clinically and genetically 
      heterogeneous malignancies, thus a comprehensive understanding of underlying 
      molecular characteristics, prognostic signatures, and potential therapeutic 
      targets is urgently needed. METHODS: Next-generation sequencing (NGS) and 
      immunohistochemistry were applied to acquire genomic and immune profiles of NENs 
      from 47 patients. RESULTS: Difference was distinguished based on differentiation 
      grade and primary localization. Poorly differentiated neuroendocrine carcinomas 
      (NECs) and well-differentiated neuroendocrine tumors (NETs) harbored distinct 
      molecular features; we observed that tumor mutational burden (TMB) and tumor 
      neoantigen burden (TNB) were significantly higher in NECs versus NETs. Notably, 
      we identified a 7-gene panel (MLH3, NACA, NOTCH1, NPAP1, RANBP17, TSC2, and 
      ZFHX4) as a novel prognostic signature in NENs; patients who carried mutations in 
      any of the 7 genes exhibited significantly poorer survival. Furthermore, loss of 
      heterozygosity (LOH) and germline homogeneity in human leukocyte antigen (HLA) 
      are common in NENs, accounting for 39% and 36%, respectively. Notably, HLA LOH 
      was an important prognostic biomarker for a subgroup of NEN patients. Finally, we 
      analyzed clinically actionable targets in NENs, revealing that TMB high (TMB-H) 
      or gene mutations in TP53, KRAS, and HRAS were the most frequently observed 
      therapeutic indicators, which granted eligibility to immune checkpoint blockade 
      (ICB) and targeted therapy. CONCLUSION: Our study revealed heterogeneity of NENs, 
      and identified novel prognostic signatures and potential therapeutic targets, 
      which directing improvements of clinical management for NEN patients in the 
      foreseeable future.
CI  - (c) The Author(s) 2023. Published by Oxford University Press.
FAU - Liu, Man
AU  - Liu M
AD  - Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, People's Republic of China.
FAU - Li, Na
AU  - Li N
AD  - Department of Translational Medicine, YuceBio Technology Co., Ltd, Shenzhen, 
      People's Republic of China.
FAU - Tang, Hongzhen
AU  - Tang H
AD  - Department of Medicine, YuceBio Technology Co., Ltd, Shenzhen, People's Republic 
      of China.
FAU - Chen, Luohai
AU  - Chen L
AD  - Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, People's Republic of China.
FAU - Liu, Xuemei
AU  - Liu X
AD  - Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital 
      of Zunyi Medical University, Zunyi, People's Republic of China.
FAU - Wang, Yu
AU  - Wang Y
AD  - Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, People's Republic of China.
FAU - Lin, Yuan
AU  - Lin Y
AD  - Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, 
      Guangzhou, People's Republic of China.
FAU - Luo, Yanji
AU  - Luo Y
AD  - Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, 
      Guangzhou, People's Republic of China.
FAU - Wei, Shaozhen
AU  - Wei S
AD  - Department of Translational Medicine, YuceBio Technology Co., Ltd, Shenzhen, 
      People's Republic of China.
FAU - Wen, Wenli
AU  - Wen W
AD  - Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, People's Republic of China.
FAU - Chen, Minhu
AU  - Chen M
AD  - Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, People's Republic of China.
FAU - Wang, Jiaqian
AU  - Wang J
AD  - Department of Translational Medicine, YuceBio Technology Co., Ltd, Shenzhen, 
      People's Republic of China.
FAU - Zhang, Ning
AU  - Zhang N
AD  - Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, People's Republic of China.
FAU - Chen, Jie
AU  - Chen J
AD  - Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, People's Republic of China.
AD  - Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, 
      Shanghai, People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Humans
MH  - Prognosis
MH  - *Neuroendocrine Tumors/therapy/drug therapy
MH  - *Carcinoma, Neuroendocrine/genetics/therapy/pathology
MH  - Biomarkers, Tumor/genetics
MH  - Mutation
MH  - *Pancreatic Neoplasms/pathology
PMC - PMC10485279
OTO - NOTNLM
OT  - genomic profile
OT  - heterogeneity
OT  - immune signature
OT  - neuroendocrine neoplasms
OT  - prognostic signature
OT  - therapeutic target
COIS- The authors indicated no financial relationships.
EDAT- 2023/04/22 19:42
MHDA- 2023/09/11 06:43
PMCR- 2023/04/22
CRDT- 2023/04/22 17:22
PHST- 2022/11/04 00:00 [received]
PHST- 2023/03/11 00:00 [accepted]
PHST- 2023/09/11 06:43 [medline]
PHST- 2023/04/22 19:42 [pubmed]
PHST- 2023/04/22 17:22 [entrez]
PHST- 2023/04/22 00:00 [pmc-release]
AID - 7136679 [pii]
AID - oyad093 [pii]
AID - 10.1093/oncolo/oyad093 [doi]
PST - ppublish
SO  - Oncologist. 2023 Sep 7;28(9):e723-e736. doi: 10.1093/oncolo/oyad093.