Background: Rectal neuroendocrine neoplasms (NENs) are rare neoplasms with limited understanding of its genomic alterations and molecular typing.
Methods: The paraffin-embedded tissue specimens of 38 patients with rectal NENs after surgery were subjected to whole gene sequencing (WGS), and mutation profilings were drawn to identify high-frequency mutation genes, copy-number variations (CNVs), tumor mutation burden (TMB), signal pathways, mutation signatures, DNA damage repair (DDR) genes, and molecular types. The differences of mutated genes and signaling pathways in different pathological grades and metastatic/non-metastatic groups were compared. It helped to search for potential targets.
Results: C > T and T > C transitions are the most common base substitutions in rectal NENs. DNA mismatch repair deficiency, DNA base modifications, smoking and exposure to ultraviolet light might play a role in the occurrence of rectal NENs. DAXX, KMT2C, BCL2L1, LTK, MERTK, SPEN, PKN1, FAT3, and LRP2 mutations were found in only low-grade rectal NETs, whereas APC, TP53, NF1, SOX9, and BRCA1 mutations were common in high-grade rectal NECs/MiNENs. These genes helped in distinguishing poorly-differentiated or well-differentiated rectal NENs. Alterations in P53, Wnt and TGFβ signaling pathways were more pronounced in rectal NECs and MiNENs. Alterations in Wnt, MAPK and PI3K/AKT signaling pathways promoted metastases. Rectal NENs were classified into two molecular subtypes by cluster analysis based on the mutant genes and signaling pathways combined with clinicopathological features. Patients with mutations in the LRP2, DAXX, and PKN1 gene showed a trend of well-differentiated and early-stage tumors with less metastasis (p = 0.000).
Conclusions: This study evaluated risk factors for regional lymphatic and/or distant metastases, identified high-frequency mutated genes, mutation signatures, altered signaling pathways through NGS. Rectal NENs were divided into two molecular types. This helps to evaluate the likelihood of metastasis, formulate follow-up strategies for patients and provide a target for future research on precision treatment of rectal NENs. PARP inhibitors, MEK inhibitors, mTOR/AKT/PI3K and Wnt signaling pathway inhibitors may be effective drugs for the treatment of metastatic rectal NENs.
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http://dx.doi.org/10.1002/cam4.6281 | DOI Listing |
World J Gastroenterol
November 2024
Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen 518000, Guangdong Province, China.
The GATIS score, developed by Zeng , represents a significant advancement in predicting the prognosis of patients with rectal neuroendocrine neoplasms (R-NENs). This study, which included 1408 patients from 17 major medical centres in China over 12 years, introduces a novel prognostic model based on the tumour grade, T stage, tumour size, age, and the prognostic nutritional index. Compared with traditional methods such as the World Health Organization classification and TNM staging systems, the GATIS score has superior predictive power for overall survival and progression-free survival.
View Article and Find Full Text PDFCurr Treat Options Oncol
November 2024
Neuroendocrine Tumour Unit, King's College Hospital, London, UK.
Am J Gastroenterol
September 2024
Department of Gastroenterology, Kyoto Second Red Cross Hospital, Kyoto, Japan.
Turk J Gastroenterol
June 2024
Department of Gastroenterology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China.
Background/aims: Although endoscopic resection is an effective treatment of rectal neuroendocrine neoplasms (R-NENs) with low malignant potential, there is no consensus on the most recommended endoscopic method. This study aimed to assess the efficacy and acceptability of different endoscopic treatments for R-NENs with low malignant potential.
Materials And Methods: We searched databases for studies on treatments of R-NENs using endoscopic resection.
World J Gastroenterol
July 2024
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, Hubei Province,
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