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 languageEnglish
    Pages (from-to)2610-2620
    Number of pages11
    JournalComputational and Structural Biotechnology Journal
    Volume18
    Early online date20 Sep 2020
    DOIs
    Publication statusPublished - 20 Sep 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.

    Keywords

    • Chemoresistance
    • GAC
    • GNEC
    • NeuroD1
    • Transcriptome analysis

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