Molecular features of gastroenteropancreatic neuroendocrine carcinoma:A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

Jianwei Zhang ¹Hanxiao Chen ²Junli Zhang ³Sha Wang ³Yanfang Guan ⁴Wenguang Gu ⁴Jie Li ⁵Xiaotian Zhang ⁶Jian Li ⁶Xicheng Wang ⁵Zhihao Lu ⁵Jun Zhou ⁵Zhi Peng ⁶Yu Sun ⁷Yang Shao ³Lin Shen ⁶Minglei Zhuo ²Ming Lu⁶

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作者信息

1. Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Gastrointestinal Oncology,Peking University Cancer Hospital & Institute,Beijing 100142,China;Department of Radiation Therapy,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen 518172,China
2. Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department Ⅰ of Thoracic Oncology,Peking University Cancer Hospital & Institute,Beijing 100142,China
3. Medical Department,Nanjing Geneseeq Technology Inc.,Nanjing 210061,China
4. Geneplus-Beijing,Beijing 102200,China
5. Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Gastrointestinal Oncology,Peking University Cancer Hospital & Institute,Beijing 100142,China
6. State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers,Beijing Key Laboratory of Carcinogenesis and Translational Research,Department of Gastrointestinal Oncology,Peking University Cancer Hospital & Institute,Beijing 100142,China
7. Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Pathology,Peking University Cancer Hospital & Institute,Beijing 100142,China
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Abstract

Objective:There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC)should follow the guidelines of small-cell lung cancer(SCLC).We aim to identify the genetic differences of GEPNEC and its counterpart.Methods:We recruited GEPNEC patients as the main cohort,with lung NEC and digestive adenocarcinomas as comparative cohorts.All patients undergone next-generation sequencing(NGS).Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC),GEPNEC and adenocarcinoma to yield the remarkable genes.Results:We recruited 257 patients,including 99 GEPNEC,57 LNEC,and 101 digestive adenocarcinomas.Among the mutations,KRAS,RB1,TERT,IL7R,and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples.Specific genes for each site were revealed:gastric NEC(TERT amplification),colorectal NEC(KRAS mutation),and bile tract NEC(ARID1A mutation).The gene disparities between small-cell NEC(SCNEC)and large-cell NEC(LCNEC)were KEAP1 and CDH1.Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1,APC,and KRAS as significant genes.The TP53/RB1 mutation pattern was associated with first-line effectiveness.Putative targetable genes and biomarkers in GEPNEC were identified in 22.2％of the patients,and they had longer progression-free survival(PFS)upon targetable treatment[12.5 months vs.3.0 months,HR=0.40(0.21-0.75),P=0.006].Conclusions:This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

Key words

Neuroendocrine carcinoma/gastroenteropancreatic/lung/genetic alterations/molecular markers

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基金项目

Major Program of National Natural Science Foundation of China(91959205)

National Natural Science Foundation of China(82141117)

Capital's Funds for Health Improvement and Research(CFH)(2022-2-1023)

Beijing Xisike Clinical Oncology Research Foundation Y-pierrefabre(202101-0099)

Beijing Municipal Administration of Hospitals Incubating Program(PX2020045)

Science Foundation of Peking University Cancer Hospital(2020-4)

出版年

2024

中国癌症研究(英文版)

中国抗癌协会北京市肿瘤研究所

中国癌症研究(英文版)

CSTPCDCSCD

影响因子：1.592

ISSN：1000-9604

参考文献量53

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