Spatial transcriptomic characteristics of gastric cancer in young and the expression and role of TMEM176B in gastric cancer cells

Sep 23, 2026

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Gastric cancer in young (GCY) shows rising incidence and poor prognosis, while existing screening and molecular approaches lack sufficient sensitivity for uncovering pathogenesis. This open-access study applied spatial transcriptomic sequencing (ST-seq) to map transcriptomic profiles across tumor core region, cancer-adjacent tissue, and normal gastric tissue. Differential expression and pathway analyses identified extensive heterogeneous cell populations, highlight IL-17, AGE-RAGE, relaxin, HIF-1, and apoptosis signaling. Functional evaluation demonstrated TMEM176B promotes proliferation and survival and modulates apoptosis and the G0/G1 cell cycle.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

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Abstract

Background

Methods

Results

Conclusions

Background

Gastric cancer in young definition and clinical context

Spatial transcriptomic sequencing and study rationale

Jiang et al. European Journal European Journal of Medical Research (2025) 30:368 [https://doi.org/10.1186/s40001-025-02577-5](https://doi.org/10.1186/s40001-025-02577-5 of Medical Research)[ of Medical Research](https://doi.org/10.1186/s40001-025-02577-5 of Medical Research) RESEARCH Open Access Spatial transcriptomic characteristics of gastric cancer in young and the expression and role of TMEM176B in gastric cancer cells Zhenhua Jiang1,2, Yongfeng Wang3, Chi Zhang4* and Shuangyin Han 1,2* Abstract Background Gastric cancer in young (GCY) is increasing in incidence with poor prognosis. Current screening and molecular methods are inadequate, necessitating new approaches to explore its pathogenesis. This study used spatial transcriptomic sequencing (ST-seq) to analyze the cellular composition of gastric cancer (GC) tumors, compare gene expression patterns, explore signaling pathways, and investigate the role of the differentially expressed gene (DEG) TMEM176B in GCY. Methods The surgical specimens of six patients with GCY were included to construct a tissue microarray containing the tumor core region (TCR), cancer-adjacent tissue (CAT), and normal gastric tissue (NGT) . ST-seq was performed to obtain the transcript expression levels at different spatial locations. After quality control, normalization, standardization, clustering, dimensionality reduction, and cell-type prediction analyses were carried out to identify the DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to clarify the underlying mechanisms of GC. Based on the results, TMEM176B was selected for functional analysis. Western blotting was used to assess TMEM176B expression in normal gastric cells and cancerous cells. shRNA-mediated TMEM176B knockdown in cancer cells was used for phenotypic analysis, proliferation assays, and apoptosis experiments. Results This study identified heterogeneous cell populations in GCY tissues. Exactly 18,082 DEGs were found between theTCR and CAT, mainly enriched in the IL-17, AGE-RAGE, and relaxin pathways. Moreover, 17,586 DEGs were identified between theTCR and NGT, primarily related to the HIF-1 and apoptosis pathways. TMEM176B was a key DEG in theTCR vs. CAT and TCR vs. NGT comparisons. It was highly expressed in GCY tissues and GC cell lines. Further analysis using The Cancer Genome Atlas database confirmed its oncogenic effects. TMEM176B knockdown in GC cell lines inhibited cell proliferation (reduced CCK8 and colony formation), increased apoptosis (higher Bax/Bcl2 ratio), and arrested the cell cycle in the G0/G1 phase. Conclusions This study used ST-seq to map the transcriptomic profiles oftheTCR, CAT, and NGT in patients with GCY, investigating gene spatial expression patterns and tumor heterogeneity. We identified TMEM176B’s role in GC development and progression, offering molecular targets and a foundation for future treatments. Keywords Gastric cancer in young, Spatial transcriptome sequencing, TMEM176B *Correspondence: Chi Zhang [zhangchi_md@163.com](zhangchi_md@163.com)[ ](zhangchi_md@163.com)Shuangyin Han [hansyzzu@163.com](hansyzzu@163.com) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in

FAQs

What was the main goal of this study on gastric cancer in young (GCY)?

To characterize spatial transcriptomic profiles of GCY tissues, compare gene expression patterns across regions, and investigate the expression and functional role of the differentially expressed gene TMEM176B in GCY cells.

How were samples and spatial transcriptomic data collected?

Surgical specimens from six GCY patients were used to construct a tissue microarray containing tumor core region (TCR), cancer-adjacent tissue (CAT), and normal gastric tissue (NGT). ST-seq generated transcript expression levels at spatial locations, followed by quality control, normalization, clustering, dimensionality reduction, and cell-type prediction to identify DEGs.

What functional effects did TMEM176B knockdown produce in GC cell lines?

TMEM176B knockdown inhibited proliferation, increased apoptosis by altering Bax/Bcl2 ratio, and arrested the cell cycle in the G0/G1 phase.

Sep 23, 2026

Uploaded by Connor