{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:49:18Z","timestamp":1768571358648,"version":"3.49.0"},"reference-count":34,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T00:00:00Z","timestamp":1703548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2022YFC2505003"],"award-info":[{"award-number":["2022YFC2505003"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2022-12M-C&T-B-057"],"award-info":[{"award-number":["2022-12M-C&T-B-057"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>G1 and G2 colorectal neuroendocrine neoplasms (NENs) are a group of rare and indolent diseases. We aimed to delineate their genetic characteristics and explore their metastatic mechanisms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used next-generation sequencing technology for targeted sequencing for 54 patients with G1 and G2 colorectal NENs. We delineated their genetic features and compared the genetic characteristics between metastatic NENs and nonmetastatic NENs. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was utilized to explore their abnormal pathways and study their potential metastatic mechanisms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We collected 23 metastatic NENs and 31 nonmetastatic NENs. In the whole cohort, the common mutated genes were NCOR2, BRD4, MDC1, ARID1A, AXIN2, etc. The common copy number variations (CNVs) included amplification of HIST1H3D, amplification of HIST1H3E, and loss of PTEN. The KEGG enrichment analysis revealed that PI3K-Akt, MAPK, and Rap1 were the major abnormal pathways. There were significantly different genetic features between metastatic NENs and nonmetastatic NENs. The metastatic NENs shared only 47 (22.5%) mutated genes and 6 (13.3%) CNVs with nonmetastatic NENs. NCOR2, BRD4, CDKN1B, CYP3A5, and EIF1AX were the commonly mutated genes in metastatic NENs, while NCOR2, MDC1, AXIN2, PIK3C2G, and PTPRT were the commonly mutated genes in nonmetastatic NENs. Metastatic NENs presented a significantly higher proportion of abnormal pathways of cell senescence (56.5% vs 25.8%, P = .022) and lysine degradation (43.5% vs 16.1%, P = .027) than nonmetastatic NENs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>G1 and G2 colorectal NENs are a group of heterogeneous diseases that might obtain an increased invasive ability through aberrant cell senescence and lysine degradation pathways.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jendso\/bvad168","type":"journal-article","created":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T16:17:34Z","timestamp":1703607454000},"source":"Crossref","is-referenced-by-count":1,"title":["Analysis of the Genetic Characteristics and Metastatic Pathways of G1 and G2 Colorectal Neuroendocrine Neoplasms"],"prefix":"10.1210","volume":"8","author":[{"given":"Zhijie","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute , Beijing 100142 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qichen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center , Guangzhou 510060 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuqiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7322-4975","authenticated-orcid":false,"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100021 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2023,12,26]]},"reference":[{"issue":"1","key":"2024011616210463000_bvad168-B1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1177\/2050640619865113","article-title":"Change in incidence, characteristics and management of colorectal neuroendocrine tumours in The Netherlands in the last decade","volume":"8","author":"Kooyker","year":"2020","journal-title":"United European Gastroenterol 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