Exploration of gastric neuroendocrine carcinoma (GNEC) specific signaling pathways involved in chemoresistance via transcriptome and in vitro analysis

Jianwei Xie; Pengchen Chen; Hongteng Xie; Yuqin Sun; Zhen Huang; Ran Wei; Zhengqiang Miao; Qingshui Wang; Shu Dong Zhang; Koon Ho Wong; Yao Lin; Changming Huang; Hang Fai Kwok

doi:10.1016/j.csbj.2020.09.016

Exploration of gastric neuroendocrine carcinoma (GNEC) specific signaling pathways involved in chemoresistance via transcriptome and in vitro analysis

Jianwei Xie, Pengchen Chen, Hongteng Xie, Yuqin Sun, Zhen Huang, Ran Wei, Zhengqiang Miao, Qingshui Wang, Shu Dong Zhang, Koon Ho Wong, Yao Lin, Changming Huang, Hang Fai Kwok

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Abstract

Gastric neuroendocrine carcinoma (GNEC) is rare cancer detected in the stomach. Previously, we demonstrated that the poorer prognosis of GNEC patients compared with gastric adenocarcinoma (GAC) patients was probably due to the lack of response to chemotherapy. Thus, it is crucial to study the specific GNEC gene expression pattern and investigate chemoresistance mechanism of GNEC. The transcriptome of GNEC patients was compared with that of GAC patients using RNA-seq. The KEGG analysis was employed to explore the specific differential expression gene function enrichment pattern. In addition, the transcriptomes of two GNEC cell lines, ECC10 and ECC12, were also compared with those of two GAC cell lines, MGC-803 and AGS, using RNA-seq. Comparing patient samples and cell lines transcriptome data, we try to uncover the potential targets and pathways which may affect the chemoresistance of GNEC. By combing all transcriptome data, we identified 22 key genes that were specifically up-regulated in GNEC. This panel of genes probably involves in the chemoresistance of GNEC. From our current experimental data, NeuroD1, one of the 22 genes, is associated with the prognosis of GNEC patients. Knockdown of NeuroD1 enhanced the sensitivity to irinotecan of GNEC cell lines. Our research sheds light in identifying a panel of novel therapeutic target specifically for GNEC clinical treatment which has not been reported before. [Abstract copyright: © 2020 The Author(s).]

Original language	English
Pages (from-to)	2610-2620
Number of pages	11
Journal	Computational and Structural Biotechnology Journal
Volume	18
Early online date	20 Sept 2020
DOIs	https://doi.org/10.1016/j.csbj.2020.09.016
Publication status	Published (in print/issue) - 20 Sept 2020

Bibliographical note

Funding Information:
The authors would like to thank the Fujian Medical University Union Hospital, the College of Life Sciences in Fujian Normal University and the Genomics, Bioinformatics & Single Cell Analysis Core at the Faculty of Health Sciences University of Macau for providing experimental equipment and technical support. CH, HFK and YL designed the study. JX, PC, HX, YS, ZH, KHW, ZM, SDZ, and QW performed experiments and participated in analyses of data; PC, HX and RW performed manuscript drafting. CH, HFK and YL revised the manuscript. All authors read and approved the final manuscript. The study was approved by the ethics committee of Fujian Medical University Union Hospital (Fujian, China; 2017KY090). Human tissue specimens collected for this study were from residual tissue in blocks generated for gastrectomy processing. All patients signed informed consents agreeing on further examinations and investigations. All data and materials generated during and/or analysed during the current study are available from the corresponding author on reasonable request. This work was supported by National Natural Science Foundation of China (No. 81871899), the International S&T Cooperation Program of China (2016YFE0121900), the Scientific Research Innovation Team Construction Program of Fujian Normal University (IRTL1702), the United Fujian Provincial Health & Education Project for Tackling the Key Research (WKJ2016-2-27), the Natural Science Foundation of Fujian Province (2016Y0029), the Science and Technology Development Fund, Macau SAR (File no. 0055/2019/A1), the Scientific and Technological Innovation Joint Capital Projects of Fujian Province (2016Y9031), the National Key Clinical Specialty Discipline Construction Program of China (No. [2012]649), the Chinese Society of Clinical Oncology (Y-N2014-008), and the Medical Innovation Projects of Fujian Province (2015-CXB-16).

Funding Information:
This work was supported by National Natural Science Foundation of China (No. 81871899 ), the International S&T Cooperation Program of China ( 2016YFE0121900 ), the Scientific Research Innovation Team Construction Program of Fujian Normal University (IRTL1702), the United Fujian Provincial Health & Education Project for Tackling the Key Research ( WKJ2016-2-27 ), the Natural Science Foundation of Fujian Province ( 2016Y0029 ), the Science and Technology Development Fund, Macau SAR (File no. 0055/2019/A1), the Scientific and Technological Innovation Joint Capital Projects of Fujian Province (2016Y9031), the National Key Clinical Specialty Discipline Construction Program of China (No. [2012]649), the Chinese Society of Clinical Oncology (Y-N2014-008), and the Medical Innovation Projects of Fujian Province (2015-CXB-16).

Publisher Copyright:
© 2020 The Author(s)

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Funding

This work was supported by National Natural Science Foundation of China (No. 81871899 ), the International S&T Cooperation Program of China ( 2016YFE0121900 ), the Scientific Research Innovation Team Construction Program of Fujian Normal University (IRTL1702), the United Fujian Provincial Health & Education Project for Tackling the Key Research ( WKJ2016-2-27 ), the Natural Science Foundation of Fujian Province ( 2016Y0029 ), the Science and Technology Development Fund, Macau SAR (File no. 0055/2019/A1), the Scientific and Technological Innovation Joint Capital Projects of Fujian Province (2016Y9031), the National Key Clinical Specialty Discipline Construction Program of China (No. [2012]649), the Chinese Society of Clinical Oncology (Y-N2014-008), and the Medical Innovation Projects of Fujian Province (2015-CXB-16).

Keywords

Chemoresistance
GAC
GNEC
NeuroD1
Transcriptome analysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.csbj.2020.09.016

2020-Comp-Struct-Biotech-GastricFinal published version, 4.07 MBLicence: CC BY-NC-ND

Cite this

Xie, J., Chen, P., Xie, H., Sun, Y., Huang, Z., Wei, R., Miao, Z., Wang, Q., Zhang, S. D., Wong, K. H., Lin, Y., Huang, C., & Kwok, H. F. (2020). Exploration of gastric neuroendocrine carcinoma (GNEC) specific signaling pathways involved in chemoresistance via transcriptome and in vitro analysis. Computational and Structural Biotechnology Journal, 18, 2610-2620. https://doi.org/10.1016/j.csbj.2020.09.016

@article{5ea90e87ad764ecd9ccd8a6e9be352f7,

title = "Exploration of gastric neuroendocrine carcinoma (GNEC) specific signaling pathways involved in chemoresistance via transcriptome and in vitro analysis",

abstract = "Gastric neuroendocrine carcinoma (GNEC) is rare cancer detected in the stomach. Previously, we demonstrated that the poorer prognosis of GNEC patients compared with gastric adenocarcinoma (GAC) patients was probably due to the lack of response to chemotherapy. Thus, it is crucial to study the specific GNEC gene expression pattern and investigate chemoresistance mechanism of GNEC. The transcriptome of GNEC patients was compared with that of GAC patients using RNA-seq. The KEGG analysis was employed to explore the specific differential expression gene function enrichment pattern. In addition, the transcriptomes of two GNEC cell lines, ECC10 and ECC12, were also compared with those of two GAC cell lines, MGC-803 and AGS, using RNA-seq. Comparing patient samples and cell lines transcriptome data, we try to uncover the potential targets and pathways which may affect the chemoresistance of GNEC. By combing all transcriptome data, we identified 22 key genes that were specifically up-regulated in GNEC. This panel of genes probably involves in the chemoresistance of GNEC. From our current experimental data, NeuroD1, one of the 22 genes, is associated with the prognosis of GNEC patients. Knockdown of NeuroD1 enhanced the sensitivity to irinotecan of GNEC cell lines. Our research sheds light in identifying a panel of novel therapeutic target specifically for GNEC clinical treatment which has not been reported before. [Abstract copyright: {\textcopyright} 2020 The Author(s).]",

keywords = "Chemoresistance, GAC, GNEC, NeuroD1, Transcriptome analysis",

author = "Jianwei Xie and Pengchen Chen and Hongteng Xie and Yuqin Sun and Zhen Huang and Ran Wei and Zhengqiang Miao and Qingshui Wang and Zhang, \{Shu Dong\} and Wong, \{Koon Ho\} and Yao Lin and Changming Huang and Kwok, \{Hang Fai\}",

note = "Funding Information: The authors would like to thank the Fujian Medical University Union Hospital, the College of Life Sciences in Fujian Normal University and the Genomics, Bioinformatics \& Single Cell Analysis Core at the Faculty of Health Sciences University of Macau for providing experimental equipment and technical support. CH, HFK and YL designed the study. JX, PC, HX, YS, ZH, KHW, ZM, SDZ, and QW performed experiments and participated in analyses of data; PC, HX and RW performed manuscript drafting. CH, HFK and YL revised the manuscript. All authors read and approved the final manuscript. The study was approved by the ethics committee of Fujian Medical University Union Hospital (Fujian, China; 2017KY090). Human tissue specimens collected for this study were from residual tissue in blocks generated for gastrectomy processing. All patients signed informed consents agreeing on further examinations and investigations. All data and materials generated during and/or analysed during the current study are available from the corresponding author on reasonable request. This work was supported by National Natural Science Foundation of China (No. 81871899), the International S\&T Cooperation Program of China (2016YFE0121900), the Scientific Research Innovation Team Construction Program of Fujian Normal University (IRTL1702), the United Fujian Provincial Health \& Education Project for Tackling the Key Research (WKJ2016-2-27), the Natural Science Foundation of Fujian Province (2016Y0029), the Science and Technology Development Fund, Macau SAR (File no. 0055/2019/A1), the Scientific and Technological Innovation Joint Capital Projects of Fujian Province (2016Y9031), the National Key Clinical Specialty Discipline Construction Program of China (No. [2012]649), the Chinese Society of Clinical Oncology (Y-N2014-008), and the Medical Innovation Projects of Fujian Province (2015-CXB-16). Funding Information: This work was supported by National Natural Science Foundation of China (No. 81871899 ), the International S\&T Cooperation Program of China ( 2016YFE0121900 ), the Scientific Research Innovation Team Construction Program of Fujian Normal University (IRTL1702), the United Fujian Provincial Health \& Education Project for Tackling the Key Research ( WKJ2016-2-27 ), the Natural Science Foundation of Fujian Province ( 2016Y0029 ), the Science and Technology Development Fund, Macau SAR (File no. 0055/2019/A1), the Scientific and Technological Innovation Joint Capital Projects of Fujian Province (2016Y9031), the National Key Clinical Specialty Discipline Construction Program of China (No. [2012]649), the Chinese Society of Clinical Oncology (Y-N2014-008), and the Medical Innovation Projects of Fujian Province (2015-CXB-16). Publisher Copyright: {\textcopyright} 2020 The Author(s) Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = sep,

day = "20",

doi = "10.1016/j.csbj.2020.09.016",

language = "English",

volume = "18",

pages = "2610--2620",

journal = "Computational and Structural Biotechnology Journal",

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Xie, J, Chen, P, Xie, H, Sun, Y, Huang, Z, Wei, R, Miao, Z, Wang, Q, Zhang, SD, Wong, KH, Lin, Y, Huang, C & Kwok, HF 2020, 'Exploration of gastric neuroendocrine carcinoma (GNEC) specific signaling pathways involved in chemoresistance via transcriptome and in vitro analysis', Computational and Structural Biotechnology Journal, vol. 18, pp. 2610-2620. https://doi.org/10.1016/j.csbj.2020.09.016

TY - JOUR

T1 - Exploration of gastric neuroendocrine carcinoma (GNEC) specific signaling pathways involved in chemoresistance via transcriptome and in vitro analysis

AU - Xie, Jianwei

AU - Chen, Pengchen

AU - Xie, Hongteng

AU - Sun, Yuqin

AU - Huang, Zhen

AU - Wei, Ran

AU - Miao, Zhengqiang

AU - Wang, Qingshui

AU - Zhang, Shu Dong

AU - Wong, Koon Ho

AU - Lin, Yao

AU - Huang, Changming

AU - Kwok, Hang Fai

N1 - Funding Information: The authors would like to thank the Fujian Medical University Union Hospital, the College of Life Sciences in Fujian Normal University and the Genomics, Bioinformatics & Single Cell Analysis Core at the Faculty of Health Sciences University of Macau for providing experimental equipment and technical support. CH, HFK and YL designed the study. JX, PC, HX, YS, ZH, KHW, ZM, SDZ, and QW performed experiments and participated in analyses of data; PC, HX and RW performed manuscript drafting. CH, HFK and YL revised the manuscript. All authors read and approved the final manuscript. The study was approved by the ethics committee of Fujian Medical University Union Hospital (Fujian, China; 2017KY090). Human tissue specimens collected for this study were from residual tissue in blocks generated for gastrectomy processing. All patients signed informed consents agreeing on further examinations and investigations. All data and materials generated during and/or analysed during the current study are available from the corresponding author on reasonable request. This work was supported by National Natural Science Foundation of China (No. 81871899), the International S&T Cooperation Program of China (2016YFE0121900), the Scientific Research Innovation Team Construction Program of Fujian Normal University (IRTL1702), the United Fujian Provincial Health & Education Project for Tackling the Key Research (WKJ2016-2-27), the Natural Science Foundation of Fujian Province (2016Y0029), the Science and Technology Development Fund, Macau SAR (File no. 0055/2019/A1), the Scientific and Technological Innovation Joint Capital Projects of Fujian Province (2016Y9031), the National Key Clinical Specialty Discipline Construction Program of China (No. [2012]649), the Chinese Society of Clinical Oncology (Y-N2014-008), and the Medical Innovation Projects of Fujian Province (2015-CXB-16). Funding Information: This work was supported by National Natural Science Foundation of China (No. 81871899 ), the International S&T Cooperation Program of China ( 2016YFE0121900 ), the Scientific Research Innovation Team Construction Program of Fujian Normal University (IRTL1702), the United Fujian Provincial Health & Education Project for Tackling the Key Research ( WKJ2016-2-27 ), the Natural Science Foundation of Fujian Province ( 2016Y0029 ), the Science and Technology Development Fund, Macau SAR (File no. 0055/2019/A1), the Scientific and Technological Innovation Joint Capital Projects of Fujian Province (2016Y9031), the National Key Clinical Specialty Discipline Construction Program of China (No. [2012]649), the Chinese Society of Clinical Oncology (Y-N2014-008), and the Medical Innovation Projects of Fujian Province (2015-CXB-16). Publisher Copyright: © 2020 The Author(s) Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/9/20

Y1 - 2020/9/20

N2 - Gastric neuroendocrine carcinoma (GNEC) is rare cancer detected in the stomach. Previously, we demonstrated that the poorer prognosis of GNEC patients compared with gastric adenocarcinoma (GAC) patients was probably due to the lack of response to chemotherapy. Thus, it is crucial to study the specific GNEC gene expression pattern and investigate chemoresistance mechanism of GNEC. The transcriptome of GNEC patients was compared with that of GAC patients using RNA-seq. The KEGG analysis was employed to explore the specific differential expression gene function enrichment pattern. In addition, the transcriptomes of two GNEC cell lines, ECC10 and ECC12, were also compared with those of two GAC cell lines, MGC-803 and AGS, using RNA-seq. Comparing patient samples and cell lines transcriptome data, we try to uncover the potential targets and pathways which may affect the chemoresistance of GNEC. By combing all transcriptome data, we identified 22 key genes that were specifically up-regulated in GNEC. This panel of genes probably involves in the chemoresistance of GNEC. From our current experimental data, NeuroD1, one of the 22 genes, is associated with the prognosis of GNEC patients. Knockdown of NeuroD1 enhanced the sensitivity to irinotecan of GNEC cell lines. Our research sheds light in identifying a panel of novel therapeutic target specifically for GNEC clinical treatment which has not been reported before. [Abstract copyright: © 2020 The Author(s).]

AB - Gastric neuroendocrine carcinoma (GNEC) is rare cancer detected in the stomach. Previously, we demonstrated that the poorer prognosis of GNEC patients compared with gastric adenocarcinoma (GAC) patients was probably due to the lack of response to chemotherapy. Thus, it is crucial to study the specific GNEC gene expression pattern and investigate chemoresistance mechanism of GNEC. The transcriptome of GNEC patients was compared with that of GAC patients using RNA-seq. The KEGG analysis was employed to explore the specific differential expression gene function enrichment pattern. In addition, the transcriptomes of two GNEC cell lines, ECC10 and ECC12, were also compared with those of two GAC cell lines, MGC-803 and AGS, using RNA-seq. Comparing patient samples and cell lines transcriptome data, we try to uncover the potential targets and pathways which may affect the chemoresistance of GNEC. By combing all transcriptome data, we identified 22 key genes that were specifically up-regulated in GNEC. This panel of genes probably involves in the chemoresistance of GNEC. From our current experimental data, NeuroD1, one of the 22 genes, is associated with the prognosis of GNEC patients. Knockdown of NeuroD1 enhanced the sensitivity to irinotecan of GNEC cell lines. Our research sheds light in identifying a panel of novel therapeutic target specifically for GNEC clinical treatment which has not been reported before. [Abstract copyright: © 2020 The Author(s).]

KW - Chemoresistance

KW - GAC

KW - GNEC

KW - NeuroD1

KW - Transcriptome analysis

UR - https://www.scopus.com/pages/publications/85091742873

U2 - 10.1016/j.csbj.2020.09.016

DO - 10.1016/j.csbj.2020.09.016

M3 - Article

C2 - 33033581

AN - SCOPUS:85091742873

SN - 2001-0370

VL - 18

SP - 2610

EP - 2620

JO - Computational and Structural Biotechnology Journal

JF - Computational and Structural Biotechnology Journal

ER -

Exploration of gastric neuroendocrine carcinoma (GNEC) specific signaling pathways involved in chemoresistance via transcriptome and in vitro analysis

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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