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

Comput Struct Biotechnol J. 2020 Sep 20:18:2610-2620. doi: 10.1016/j.csbj.2020.09.016. eCollection 2020.

Authors

Jianwei Xie¹, Pengchen Chen², Hongteng Xie¹, Yuqin Sun^{1

3}, Zhen Huang⁴, Ran Wei², Zhengqiang Miao², Qingshui Wang⁴, Shu-Dong Zhang⁵, Koon Ho Wong², Yao Lin^{4

6}, Changming Huang¹, Hang Fai Kwok²

Affiliations

¹ Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350000, PR China.
² Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR.
³ Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, PR China.
⁴ College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350000, PR China.
⁵ Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster University, Londonderry BT47, United Kingdom.
⁶ Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University, Fuzhou, Fujian 350000, PR China.

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.

Keywords: Chemoresistance; GAC; GNEC; NeuroD1; Transcriptome analysis.