Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2022; 14(11): 2097-2107
Published online Nov 15, 2022. doi: 10.4251/wjgo.v14.i11.2097
Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis
Li-Hua Zhang, Hui-Qin Zhuo, Jing-Jing Hou, Yang Zhou, Jia Cheng, Jian-Chun Cai
Li-Hua Zhang, Hui-Qin Zhuo, Jing-Jing Hou, Yang Zhou, Jia Cheng, Jian-Chun Cai, Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian Province, China
Li-Hua Zhang, Yang Zhou, Jian-Chun Cai, Institute of Gastrointestinal Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian Province, China
Hui-Qin Zhuo, Jing-Jing Hou, Jia Cheng, Jian-Chun Cai, Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian Province, China
Author contributions: Cai JC, Zhang LH and Zhuo HQ contributed conceptualization; Zhang LH, Zhuo HQ, Hou JJ, Zhou Y and Cheng J contributed methodology; Hou JJ and Cheng J contributed data curation; Zhang LH, Hou JJ, Zhou Y and Cheng J contributed formal analysis; Zhang LH and Zhou Y contributed visualization; Zhang LH and Zhuo HQ wrote the manuscript; Zhang LH, Zhuo HQ, Hou JJ, Zhou Y, Cheng J and Cai JC contributed manuscript review; Cai JC, Zhuo HQ and Hou JJ contributed supervision.
Supported by National Natural Science Foundation of China, No. 81871979; Natural Science Foundation of Fujian Province, No. 2021J02056, No. 2021J05276 and No. 2020CXB048; and Medical and Health Sciences Foundation of Xiamen, No. 3502Z20199171 and No. 3502Z20204002.
Institutional review board statement: This research was conducted with the approval of the ethical review committee of Zhongshan Hospital of Xiamen University (approval No. 2022-178) and in accordance with the guidelines of the Declaration of Helsinki.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at jianchunfh2@sina.com.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jian-Chun Cai, PhD, Professor, Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, No. 201 Hubin Road, Siming Street, Xiamen 361004, Fujian Province, China. jianchunfh2@sina.com
Received: March 25, 2022
Peer-review started: March 25, 2022
First decision: June 2, 2022
Revised: June 16, 2022
Accepted: October 17, 2022
Article in press: October 17, 2022
Published online: November 15, 2022
Abstract
BACKGROUND

Proteomic signatures of Ming's infiltrative gastric cancer (IGC) remain unknown.

AIM

To elucidate the molecular characteristics of IGC at the proteomics level.

METHODS

Twelve pairs of IGC and adjacent normal tissues were collected and their proteomes were analyzed by high performance liquid chromatography tandem mass spectrometry. The identified peptides were sequenced de novo and matched against the SwissProt database using Maxquant software. The differentially expressed proteins (DEPs) were screened using |log2(Fold change)| > 1 and P-adj < 0.01 as the thresholds. The expression levels of selected proteins were verified by Western blotting. The interaction network of the DEPs was constructed with the STRING database and visualized using Cytoscape with cytoHubba software. The DEPs were functionally annotated using clusterProfiler, STRING and DAVID for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. P < 0.05 was considered statistically significant.

RESULTS

A total of 7361 DEPs were identified, of which 94 were significantly up-regulated and 223 were significantly down-regulated in IGC relative to normal gastric tissues. The top 10 up-regulated proteins were MRTO4, BOP1, PES1, WDR12, BRIX1, NOP2, POLR1C, NOC2L, MYBBP1A and TSR1, and the top 10 down-regulated proteins were NDUFS8, NDUFS6, NDUFA8, NDUFA5, NDUFC2, NDUFB8, NDUFB5, NDUFB9, UQCRC2 and UQCRC1. The up-regulated proteins were enriched for 9 biological processes including DNA replication, ribosome biogenesis and initiation of DNA replication, and the cellular component MCM complex. Among the down-regulated proteins, 17 biological processes were enriched, including glucose metabolism, pyruvic acid metabolism and fatty acid β-oxidation. In addition, the mitochondrial inner membrane, mitochondrial matrix and mitochondrial proton transport ATP synthase complex were among the 6 enriched cellular components, and 11 molecular functions including reduced nicotinamide adenine dinucleotide dehydrogenase activity, acyl-CoA dehydrogenase activity and nicotinamide adenine dinucleotide binding were also enriched. The significant KEGG pathways for the up-regulated proteins were DNA replication, cell cycle and mismatch repair, whereas 18 pathways including oxidative phosphorylation, fatty acid degradation and phenylalanine metabolism were significantly enriched among the down-regulated proteins.

CONCLUSION

The proteins involved in cell cycle regulation, DNA replication and mismatch repair, and metabolism were significantly altered in IGC, and the proteomic profile may enable the discovery of novel biomarkers.

Keywords: Infiltrative gastric cancer, Proteomics, Molecular biological characteristics, Ming's classification, Bioinformatic analysis

Core Tip: A total of 7361 proteins were identified and 317 proteins were significantly abnormally expressed in infiltrative gastric cancer (IGC). Twenty hub proteins were found and some of them were verified in IGC. Cell cycle regulation, DNA replication and mismatch repair, and metabolism were significantly altered in IGC.