Analysis of transcriptomic differences of duodenal neuroendocrine tumor accompanied by liver and lymph node metastases_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XU Yuhang , XUE Dong , LIU Chang , HUANG Wenbo , XU Chenxi , ZHAO Wei ,  SUN Qi

1. Department of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P. R. China;

Corresponding author：

SUN Qi, Email: sunqi4875@163.com

Keywords：

duodenal neuroendocrine tumor; metastasis; RNA sequencing; functional enrichment analysis

DOI：

10.7507/1007-9424.202311039

Video：

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Objective To explore the key genes and potential molecular mechanisms of liver and lymph node metastases relevant to duodenal neuroendocrine tumors (DNET). Methods The tissues of paracancerous duodenal epithelial, primary lesion, liver metastasis lesion, and lymph node metastasis lesion of a rare DNET accompanied by liver and lymph node metastases were sequenced and analyzed. The differentially expressed genes (DEGs) were screened for different tissues and the functional enrichment analysis was performed. Results The tissues of paracancerous duodenal epithelial was used as the control, a total of 2 053 DEGs expressed only in the liver metastases lesion tissues and 742 DEGs expressed only in the lymph node metastases lesion tissues were screened out, and the top 5 genes expressed in the liver metastases lesion tissues were ORM1, C4BPA, AHSG, C9, and LBP, which in the lymph node metastases lesion tissues were ABHD12B, AC100850.1, HOXC9, AC083967.1, and HOXC8. Kyoto Encyclopedia of Genes and Genomes enrichment analysis found that the DEGs were mainly enriched in the phosphatidylinosiol 3 kinase / protein kinase B pathway, mitogen-activated protein kinase pathway, human papillomavirus infection, etc. Conclusion Multiple DEGs and pathways in metastatic lesions are found in this patient with DNET accompanied by liver metastasis and lymph node metastasis, which provides a new direction for treatment and prophylaxis of DNET.

Citation： XU Yuhang, XUE Dong, LIU Chang, HUANG Wenbo, XU Chenxi, ZHAO Wei, SUN Qi. Analysis of transcriptomic differences of duodenal neuroendocrine tumor accompanied by liver and lymph node metastases. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2024, 31(3): 309-314. doi: 10.7507/1007-9424.202311039 Copy

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5.	Sakamoto A, Nozawa H, Sonoda H, et al. Rectal neuroendocrine tumor with extracapsular lymph node metastasis: a case report. Clin J Gastroenterol, 2021, 14(5): 1426-1430.
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7.	Yang J, Nie J, Ma X, et al. Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol Cancer, 2019, 18(1): 26.
8.	Liu ST, Zhong SM, Li XY, et al. EphrinB/EphB forward signaling in Müller cells causes apoptosis of retinal ganglion cells by increasing tumor necrosis factor alpha production in rat experimental glaucomatous model. Acta Neuropathol Commun, 2018, 6(1): 111.
9.	Chander Y, Kumar R, Khandelwal N, et al. Role of p38 mitogen-activated protein kinase signalling in virus replication and potential for developing broad spectrum antiviral drugs. Rev Med Virol, 2021, 31(5): 1-16.
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14.	Oramas DM, Bell D, Middleton LP. Sinonasal analogue HPV related breast multiphenotypic carcinoma, a report of a case with the first description in the breast. Diagn Pathol, 2020, 15(1): 137.
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16.	Kang X, Sun L, Guo K, et al. Serum protein biomarkers screening in HCC patients with liver cirrhosis by ICAT-LC-MS/MS. J Cancer Res Clin Oncol, 2010, 136(8): 1151-1159.
17.	Wang YS, Cao R, Jin H, et al. Altered protein expression in serum from endometrial hyperplasia and carcinoma patients. J Hematol Oncol, 2011, 4: 15.
18.	Bhatlekar S, Fields JZ, Boman BM. Role of HOX genes in stem cell differentiation and cancer. Stem Cells Int, 2018, 2018: 3569493.
19.	Liu Y, Jing L, Zhang J. circRNA-mediated upregulation of HOXC9 is correlated with poor outcome and immune microenvironment infiltrates in LUAD. Biochem Biophys Res Commun, 2022, 635: 128-135.
20.	Cao YM, Wen D, Qu N, et al. Prognostic and clinical significance of HOXC9 and HOXD10 in papillary thyroid cancer. Transl Cancer Res, 2021, 10(7): 3317-3325.
21.	Tang Y, Wang T, Yu Y, et al. Upregulation of HOXC9 generates interferon-gamma resistance in gastric cancer by inhibiting the DAPK1/RIG1/STAT1 axis. Cancer Sci, 2021, 112(9): 3455-3468.
22.	Hur H, Lee JY, Yang S, et al. HOXC9 induces phenotypic switching between proliferation and invasion in breast cancer cells. J Cancer, 2016, 7(7): 768-773.
23.	Hu M, Ou-Yang W, Jing D, et al. Clinical prognostic significance of HOXC9 expression in patients with colorectal cancer. Clin Lab, 2019, 65(8).
24.	Contarelli S, Fedele V, Melisi D. HOX genes family and cancer: a novel role for Homeobox B9 in the resistance to anti-angiogenic therapies. Cancers (Basel), 2020, 12(11): 3299.
25.	Shah N, Sukumar S. The Hox genes and their roles in oncogenesis. Nat Rev Cancer, 2010, 10(5): 361-371.
26.	Li Y, Chao F, Huang B, et al. HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression. Oncotarget, 2014, 5(9): 2596-2607.
27.	Liu H, Zhang M, Xu S, et al. HOXC8 promotes proliferation and migration through transcriptional up-regulation of TGFβ1 in non-small cell lung cancer. Oncogenesis, 2018, 7(2): 1.
28.	Adwan H, Zhivkova-Galunska M, Georges R, et al. Expression of HOXC8 is inversely related to the progression and metastasis of pancreatic ductal adenocarcinoma. Br J Cancer, 2011, 105(2): 288-295.
29.	Axlund SD, Lambert JR, Nordeen SK. HOXC8 inhibits androgen receptor signaling in human prostate cancer cells by inhibiting SRC-3 recruitment to direct androgen target genes. Mol Cancer Res, 2010, 8(12): 1643-1655.
30.	张继朋, 卢强, 陈鹏, 等. 雌激素对肺腺癌SPC-A-1细胞上皮间质转化标志物Vimentin、E-cadherin表达量的影响. 医学临床研究, 2020, 37(10): 1450-1453.

1. Akezaki Y, Nakata E, Kikuuchi M, et al. Factors affecting the discharge destination of patients with spinal bone metastases. Ann Rehabil Med, 2020, 44(1): 69-76.
2. Cives M, Strosberg JR. Gastroenteropancreatic neuroendocrine tumors. CA Cancer J Clin, 2018, 68(6): 471-487.
3. Dasari A, Shen C, Halperin D, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol, 2017, 3(10): 1335-1342.
4. Das S, Dasari A. Epidemiology, incidence, and prevalence of neuroendocrine neoplasms: are there global differences?. Curr Oncol Rep, 2021, 23(4): 43.
5. Sakamoto A, Nozawa H, Sonoda H, et al. Rectal neuroendocrine tumor with extracapsular lymph node metastasis: a case report. Clin J Gastroenterol, 2021, 14(5): 1426-1430.
6. Frilling A, Modlin IM, Kidd M, et al. Recommendations for management of patients with neuroendocrine liver metastases. Lancet Oncol, 2014, 15(1): e8-e21.
7. Yang J, Nie J, Ma X, et al. Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol Cancer, 2019, 18(1): 26.
8. Liu ST, Zhong SM, Li XY, et al. EphrinB/EphB forward signaling in Müller cells causes apoptosis of retinal ganglion cells by increasing tumor necrosis factor alpha production in rat experimental glaucomatous model. Acta Neuropathol Commun, 2018, 6(1): 111.
9. Chander Y, Kumar R, Khandelwal N, et al. Role of p38 mitogen-activated protein kinase signalling in virus replication and potential for developing broad spectrum antiviral drugs. Rev Med Virol, 2021, 31(5): 1-16.
10. Low HB, Zhang Y. Regulatory roles of MAPK Phosphatases in cancer. Immune Netw, 2016, 16(2): 85-98.
11. Liu Y, Shepherd EG, Nelin LD. MAPK phosphatases—regulating the immune response. Nat Rev Immunol, 2007, 7(3): 202-212.
12. Fang JY, Richardson BC. The MAPK signalling pathways and colorectal cancer. Lancet Oncol, 2005, 6(5): 322-327.
13. 洪梓德, 莫志贤. 中药抗肿瘤机制中的11种信号通路. 中国实验方剂学杂志, 2018, 24(21): 205-218.
14. Oramas DM, Bell D, Middleton LP. Sinonasal analogue HPV related breast multiphenotypic carcinoma, a report of a case with the first description in the breast. Diagn Pathol, 2020, 15(1): 137.
15. Dai Y, Xie F, Chen Y. Reduced levels of miR-485-5p in HPV-infected cervical cancer promote cell proliferation and enhance invasion ability. FEBS Open Bio, 2020, 10(7): 1348-1361.
16. Kang X, Sun L, Guo K, et al. Serum protein biomarkers screening in HCC patients with liver cirrhosis by ICAT-LC-MS/MS. J Cancer Res Clin Oncol, 2010, 136(8): 1151-1159.
17. Wang YS, Cao R, Jin H, et al. Altered protein expression in serum from endometrial hyperplasia and carcinoma patients. J Hematol Oncol, 2011, 4: 15.
18. Bhatlekar S, Fields JZ, Boman BM. Role of HOX genes in stem cell differentiation and cancer. Stem Cells Int, 2018, 2018: 3569493.
19. Liu Y, Jing L, Zhang J. circRNA-mediated upregulation of HOXC9 is correlated with poor outcome and immune microenvironment infiltrates in LUAD. Biochem Biophys Res Commun, 2022, 635: 128-135.
20. Cao YM, Wen D, Qu N, et al. Prognostic and clinical significance of HOXC9 and HOXD10 in papillary thyroid cancer. Transl Cancer Res, 2021, 10(7): 3317-3325.
21. Tang Y, Wang T, Yu Y, et al. Upregulation of HOXC9 generates interferon-gamma resistance in gastric cancer by inhibiting the DAPK1/RIG1/STAT1 axis. Cancer Sci, 2021, 112(9): 3455-3468.
22. Hur H, Lee JY, Yang S, et al. HOXC9 induces phenotypic switching between proliferation and invasion in breast cancer cells. J Cancer, 2016, 7(7): 768-773.
23. Hu M, Ou-Yang W, Jing D, et al. Clinical prognostic significance of HOXC9 expression in patients with colorectal cancer. Clin Lab, 2019, 65(8).
24. Contarelli S, Fedele V, Melisi D. HOX genes family and cancer: a novel role for Homeobox B9 in the resistance to anti-angiogenic therapies. Cancers (Basel), 2020, 12(11): 3299.
25. Shah N, Sukumar S. The Hox genes and their roles in oncogenesis. Nat Rev Cancer, 2010, 10(5): 361-371.
26. Li Y, Chao F, Huang B, et al. HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression. Oncotarget, 2014, 5(9): 2596-2607.
27. Liu H, Zhang M, Xu S, et al. HOXC8 promotes proliferation and migration through transcriptional up-regulation of TGFβ1 in non-small cell lung cancer. Oncogenesis, 2018, 7(2): 1.
28. Adwan H, Zhivkova-Galunska M, Georges R, et al. Expression of HOXC8 is inversely related to the progression and metastasis of pancreatic ductal adenocarcinoma. Br J Cancer, 2011, 105(2): 288-295.
29. Axlund SD, Lambert JR, Nordeen SK. HOXC8 inhibits androgen receptor signaling in human prostate cancer cells by inhibiting SRC-3 recruitment to direct androgen target genes. Mol Cancer Res, 2010, 8(12): 1643-1655.
30. 张继朋, 卢强, 陈鹏, 等. 雌激素对肺腺癌SPC-A-1细胞上皮间质转化标志物Vimentin、E-cadherin表达量的影响. 医学临床研究, 2020, 37(10): 1450-1453.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Analysis of transcriptomic differences of duodenal neuroendocrine tumor accompanied by liver and lymph node metastases

Abstract Full text Figures/Tables Video References Cited by

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