Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 6, 2023; 11(16): 3714-3724
Published online Jun 6, 2023. doi: 10.12998/wjcc.v11.i16.3714
Helicobacter pylori plays a key role in gastric adenocarcinoma induced by spasmolytic polypeptide-expressing metaplasia
Mian-Li Li, Xin-Xin Hong, Wei-Jian Zhang, Yi-Zhong Liang, Tian-Tian Cai, Yi-Fei Xu, Hua-Feng Pan, Jian-Yuan Kang, Shao-Ju Guo, Hai-Wen Li
Mian-Li Li, Department of Gastroenterology, Shenzhen Hospital of Integrated, Traditional Chinese and Western Medicine, Shenzhen 518033, Guangdong Province, China
Xin-Xin Hong, Yi-Zhong Liang, Tian-Tian Cai, Yi-Fei Xu, Jian-Yuan Kang, Shao-Ju Guo, Hai-Wen Li, Department of Gastroenterology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, Guangdong Province, China
Wei-Jian Zhang, Hua-Feng Pan, Science and Technology Innovation Center, Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, Guangdong Province, China
Author contributions: Li ML and Li HW conceptualized the and wrote the initial manuscript; Hong XX and Zhang WJ conceptualized the table and figures; Liang YZ and Cai TT performed the literature search; Xu YF and Kang JY conceptualized the structure of the text; Pan HF and Guo SJ supervised and approved the final version of the review.
Supported by the Guangdong Basic and Applied Basic Research Foundation, No. 2020A1515110947; the National Natural Science Foundation of China, No. 82104747; the Scientific Research Project of Guangdong Bureau of Traditional Chinese Medicine, No. 20231303; and the Guangdong Provincial Key Research and Development Plan, No. 2020B1111100011.
Conflict-of-interest statement: Li HW is an employee of Shenzhen Traditional Chinese Medicine Hospital.
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:
Corresponding author: Hai-Wen Li, MD, Professor, Department of Gastroenterology, Shenzhen Traditional Chinese Medicine Hospital, No. 1 Fuhua Road, Futian District, Shenzhen 518033, Guangdong Province, China.
Received: January 4, 2023
Peer-review started: January 4, 2023
First decision: January 22, 2023
Revised: March 1, 2023
Accepted: April 23, 2023
Article in press: April 23, 2023
Published online: June 6, 2023

Heliobacter pylori (H. pylori), a group 1 human gastric carcinogen, is significantly associated with chronic gastritis, gastric mucosal atrophy, and gastric cancer. Approximately 20% of patients infected with H. pylori develop precancerous lesions, among which metaplasia is the most critical. Except for intestinal metaplasia (IM), which is characterized by goblet cells appearing in the stomach glands, one type of mucous cell metaplasia, spasmolytic polypeptide-expressing metaplasia (SPEM), has attracted much attention. Epidemiological and clinicopathological studies suggest that SPEM may be more strongly linked to gastric adenocarcinoma than IM. SPEM, characterized by abnormal expression of trefoil factor 2, mucin 6, and Griffonia simplicifolia lectin II in the deep glands of the stomach, is caused by acute injury or inflammation. Although it is generally believed that the loss of parietal cells alone is a sufficient and direct cause of SPEM, further in-depth studies have revealed the critical role of immunosignals. There is controversy regarding whether SPEM cells originate from the transdifferentiation of mature chief cells or professional progenitors. SPEM plays a functional role in the repair of gastric epithelial injury. However, chronic inflammation and immune responses caused by H. pylori infection can induce further progression of SPEM to IM, dysplasia, and adenocarcinoma. SPEM cells upregulate the expression of whey acidic protein 4-disulfide core domain protein 2 and CD44 variant 9, which recruit M2 macrophages to the wound. Studies have revealed that interleukin-33, the most significantly upregulated cytokine in macrophages, promotes SPEM toward more advanced metaplasia. Overall, more effort is needed to reveal the specific mechanism of SPEM malignant progression driven by H. pylori infection.

Keywords: Gastric cancers, Helicobacter pylori, Intestinal metaplasia, Macrophages, Spasmolytic polypeptide-expressing metaplasia

Core Tip: Spasmolytic polypeptide-expressing metaplasia (SPEM), induced by Heliobacter pylori (H. pylori) infection in humans, is strongly associated with gastric adenocarcinoma. Chronic inflammation and immune responses caused by H. pylori infection play important roles in the malignant progression of SPEM. Recent studies suggest that CD44 variant 9 and whey acidic protein 4-disulfide core domain protein 2 expressed by SPEM leads to M2 macrophage recruitment. Furthermore, M2 macrophages upregulate the expression of interleukin 33, which eventually promotes malignant progression.