Spasmolytic polypeptide-expressing metaplasia in the progression of gastric precancerous lesions: mechanisms and therapeutic opportunities-a narrative review.
- 1Graduate School, Chongqing Medical University, Chongqing, China.
- 2Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Abstract
Spasmolytic polypeptide-expressing metaplasia (SPEM) represents a gastric metaplastic phenotype situated at the intersection of mucosal repair and preneoplastic remodeling. While transient SPEM may facilitate epithelial restitution following acute injury, persistent SPEM in chronic inflammatory contexts correlates with incomplete intestinal metaplasia (IM), dysplastic epithelial states, and gastric carcinogenesis. This narrative review summarizes the biological characteristics and proposed cellular origins of SPEM. It critically examines the mechanisms governing SPEM initiation, persistence, and progression-associated remodeling. It also evaluates the evidence linking SPEM to incomplete IM and gastric carcinogenesis and discusses emerging therapeutic vulnerabilities and their translational limitations. PubMed and Web of Science were searched for English-language studies published from January 1, 2000 to April 30, 2026. Reference lists of relevant studies and guidelines were also screened. Human, animal, organoid, and other experimental studies with direct mechanistic or clinical relevance were included. The cellular origin of SPEM is model dependent. Acute models support chief-cell plasticity, whereas trefoil factor 2-expressing isthmal progenitors contribute in specific contexts. Single-cell analyses suggest convergence of mucous neck cells and chief-cell states without proving lineage conversion. SPEM involves disrupted epithelial homeostasis and paligenosis, together with growth factor, Wnt/β-catenin, and oncogenic signaling. Chronic Helicobacter pylori (H. pylori)injury, immune and stromal signals, and redox adaptation promote persistence. Human studies associate SPEM mainly with incomplete IM but do not establish obligatory progression to IM or cancer. H. pylori eradication remains the only recognized upstream intervention; SPEM-directed strategies remain preclinical. SPEM is a context-dependent reparative lineage whose association with preneoplastic remodeling is strongest in chronic injury. Human evidence links persistent SPEM to incomplete IM and dysplasia-associated states but does not establish an obligatory SPEM-to-IM-to-cancer sequence. Future progress requires distinguishing transient reparative SPEM from persistent, progression-associated SPEM, standardizing phenotypic criteria, conducting longitudinal human studies, and identifying targets that suppress pathological SPEM without impairing mucosal repair.
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BibTeX
@article{zhang2026spasmolytic,
title = {{Spasmolytic polypeptide-expressing metaplasia in the progression of gastric precancerous lesions: mechanisms and therapeutic opportunities-a narrative review.}},
author = {Xiangye Zhang and Keyan Shi and Jian Gao},
journal = {Translational cancer research},
year = {2026},
month = sep,
doi = {10.21037/tcr-2026-2039},
url = {https://europepmc.org/article/MED/42997683},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Spasmolytic polypeptide-expressing metaplasia in the progression of gastric precancerous lesions: mechanisms and therapeutic opportunities-a narrative review.
AU - Xiangye Zhang
AU - Keyan Shi
AU - Jian Gao
PY - 2026
DA - 2026/09/28
JO - Translational cancer research
DO - 10.21037/tcr-2026-2039
UR - https://europepmc.org/article/MED/42997683
AB - Spasmolytic polypeptide-expressing metaplasia (SPEM) represents a gastric metaplastic phenotype situated at the intersection of mucosal repair and preneoplastic remodeling. While transient SPEM may facilitate epithelial restitution following acute injury, persistent SPEM in chronic inflammatory contexts correlates with incomplete intestinal metaplasia (IM), dysplastic epithelial states, and gastric carcinogenesis. This narrative review summarizes the biological characteristics and proposed cellular origins of SPEM. It critically examines the mechanisms governing SPEM initiation, persistence, and progression-associated remodeling. It also evaluates the evidence linking SPEM to incomplete IM and gastric carcinogenesis and discusses emerging therapeutic vulnerabilities and their translational limitations. PubMed and Web of Science were searched for English-language studies published from January 1, 2000 to April 30, 2026. Reference lists of relevant studies and guidelines were also screened. Human, animal, organoid, and other experimental studies with direct mechanistic or clinical relevance were included. The cellular origin of SPEM is model dependent. Acute models support chief-cell plasticity, whereas trefoil factor 2-expressing isthmal progenitors contribute in specific contexts. Single-cell analyses suggest convergence of mucous neck cells and chief-cell states without proving lineage conversion. SPEM involves disrupted epithelial homeostasis and paligenosis, together with growth factor, Wnt/β-catenin, and oncogenic signaling. Chronic Helicobacter pylori (H. pylori)injury, immune and stromal signals, and redox adaptation promote persistence. Human studies associate SPEM mainly with incomplete IM but do not establish obligatory progression to IM or cancer. H. pylori eradication remains the only recognized upstream intervention; SPEM-directed strategies remain preclinical. SPEM is a context-dependent reparative lineage whose association with preneoplastic remodeling is strongest in chronic injury. Human evidence links persistent SPEM to incomplete IM and dysplasia-associated states but does not establish an obligatory SPEM-to-IM-to-cancer sequence. Future progress requires distinguishing transient reparative SPEM from persistent, progression-associated SPEM, standardizing phenotypic criteria, conducting longitudinal human studies, and identifying targets that suppress pathological SPEM without impairing mucosal repair.
SN - 2218-676X
SN - 2219-6803
ER -