EHBMT, a method for visualizing tumor evolution, identifies a surge in gastric cancer with hybrid epithelial–mesenchymal phenotypes due to an inflammatory microenvironment

Sep 23, 2026

Uploaded by nayy☆

A study proposes an EMT heterogeneity-based molecular typing (EHBMT) workflow to visualize cancer evolution from bulk transcriptomics. Gastric cancer tissues are partitioned into epithelial phenotype cluster (EPC), hybrid epithelial–mesenchymal phenotype cluster (HPC), and mesenchymal phenotype cluster (MPC). Multiplex immunohistochemistry and single-cell analyses validate feasibility, while clinical features, molecular traits, and prognosis vary by subtype. The HPC proportion sharply increases during evolution, traced to transitions from normal EPC to cancerous HPC/MPC, linked to IL-1β and EMT signaling under inflammatory microenvironments.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Introduction

Tumor heterogeneity and personalized medicine

Proposed method and rationale

EMT heterogeneity-based molecular typing (EHBMT)

Results overview

Subtype definition and clinical/prognostic differences

HPC surge and traceability to EMT signaling

[www.nature.com/emm](www.nature.com/emm) ARTICLE OPEN EHBMT, a method for visualizing tumor evolution, identiﬁes a surge in gastric cancer with hybrid epithelial–mesenchymal phenotypes due to an inﬂammatory microenvironment Dandan Li 1,2,3,4, Zeng Zhou2,4, Yuanjian Hui2, Hedong Yu2, Tao Ren2, Lantian Zhai2, Xinqi Li2, Lin Yuan2, Lingyun Xia1, Weidong Leng 1 ✉ and Shanshan Qin 1,2,3 ✉ © The Author(s) 2025, modiﬁed publication 2025 | | | | | --- | --- | --- | | | A method for analyzing tumor evolution based on bulk RNA-sequencing data has not been reported yet. The epithelial–mesenchymal transition (EMT) is an evolutionarily conserved cellular program with high heterogeneity and plasticity. In this study, we proposed an EMT heterogeneity-based molecular typing (EHBMT) method to visualize cancer evolution and guide personalized medicine. Multiplex immunohistochemical assay and single-cell analysis were performed to conﬁrm the feasibility of this method. EHBMT divided gastric (cancer) tissues into an epithelial phenotype cluster (EPC), hybrid epithelial–mesenchymal phenotype cluster (HPC) and mesenchymal phenotype cluster (MPC). Patients with gastric cancer with different EHBMT subtypes possessed distinct clinical features, molecular characteristics and prognostic outcomes. Furthermore, the proliferation ability of EPC, HPC and MPC subtypes decreases sequentially. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis showed that HPC subtypes are associated with inﬂammation and immune activation. More importantly, EHBMT discovered a sharp increase in the proportion of the HPC subtype during gastric cancer evolution. Traceability analysis indicated that the surge in HPC in gastric cancer was due to the transition from approximately 70–80% of normal EPC cases to cancerous HPC/MPC cases. In addition, the inﬂammatory factor IL-1β, highly expressed epithelial cells in the HPC subtype, should be a key driver for the decrease of epithelial cells by inducing EMT signaling. In conclusion, EHBMT is a novel method for visualizing cancer evolution using bulk transcriptomics. Gastric carcinogenesis is accompanied by a sharp increase in the proportion of HPC due to the abnormal EMT signaling pathway driven by an inﬂammatory microenvironment. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | HIGHLIGHTS | | | | ● We herein provided an epithelial–mesenchymal transition heterogeneity-based molecular typing method (EHBMT), which can be applied in normal and cancerous tissues to visualize cancer evolution and development and guide personalized medicine.
● EHBMT divided gastric (cancer) tissues into three subtypes, including an epithelial phenotype cluster (EPC), hybrid epithelial–mesenchymal phenotype cluster (HPC) and mesenchymal phenotype cluster (MPC) . Different EHBMT subtypes possess distinct proliferation abilities, molecular characteristics and clinical outcomes in gastric cancer (GC) .
● GC evolution is accompanied by a steep rise in proportion of the hybrid epithelial–mesenchymal transition subtype with signiﬁcant inﬂammatory and immune activation features.
● During GC evolution, about 70–80% of normal EPC cases were transited into cancerous HPC/MPC cases. An inﬂammatory microenvironment, especially IL-1β, should be a key driver for the transition from the normal EPC subtype to the cancerous HPC | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | subtype in GC. | | | | | Experimental & Molecular Medicine (2025) 57:2440–2457; [https://doi.org/10.1038/s12276-025-01570-6](https://doi.org/10.1038/s12276-025-01570-6) | | | | | | INTRODUCTION Malignant tumorigenesis, also known as carcinogenesis, is a complex multistep biological process with high heterogeneity1. On the one hand, there are signiﬁcant histol

FAQs

What is EHBMT and what problem does it address?

EHBMT is an EMT heterogeneity-based molecular typing method designed to visualize cancer evolution and support personalized medicine. It targets the lack of reported approaches for analyzing tumor evolution using bulk RNA-sequencing data.

How does EHBMT classify gastric cancer tissues?

EHBMT divides gastric (cancer) tissues into three clusters: EPC (epithelial), HPC (hybrid epithelial–mesenchymal), and MPC (mesenchymal).

Why does the hybrid HPC subtype increase during gastric cancer evolution?

Traceability analysis indicates the surge results from transitions from roughly 70–80% normal EPC cases into cancerous HPC/MPC. The inflammatory microenvironment—especially IL-1β expressed in highly epithelial cells within HPC—acts as a key driver by inducing EMT signaling.

Sep 23, 2026

Uploaded by nayy☆