Integrative multi-omics analysis reveals a membrane tension signature associated with tumor-stroma crosstalk in hepatocellular carcinoma.

Authors

Pengfei Zhu, Pengcheng Zhu, Zijuan Zhu, Gaozhong Bian, Yungang Liu, Qifan Yang, Peipei Luo

Published in

Frontiers in immunology. Volume 17. Pages 1978174. Epub Oct 05, 2026.

Abstract

Dysregulated membrane tension (MT) drives tumor cell migration, invasion, and immune evasion, yet the prognostic value of MT-related genes (MTRGs) in hepatocellular carcinoma (HCC) remains unclear.
We integrated transcriptomic and clinical data from TCGA, ICGC, and GEO. A three-gene MTRG prognostic signature was developed through univariate and LASSO-Cox regression, and validated using Kaplan-Meier analysis, time-dependent ROC curves, and calibration plots. Functional enrichment, immune infiltration, tumor mutational burden, and immunotherapy response was predicted using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Single-cell and spatial transcriptomics were used to investigate the mechanistic role of CFL1 in tumor-stroma crosstalk.
The signature (CFL1, CRTC2, SRGAP2) stratified HCC patients into high- and low-risk groups with distinct overall survival (OS). High-risk tumors showed coordinated activation of MT and ECM-remodeling pathways alongside an immunosuppressive microenvironment. In silico analyses suggested that CFL1-high tumor cells may transmit MDK signals to fibroblasts (via SDC2, NCL, and ITGA4-ITGB1) and to T cells (via NCL). Spatial transcriptomics confirmed predominant CFL1 enrichment in stromal compartments. The signature was an independent prognostic factor, and the nomogram showed promising clinical utility.
This three-gene MTRG-associated signature is associated with predicted immunotherapy response based on computational analysis in HCC. Our results suggest a potential link between biophysical MT and tumor stroma co evolution and represent a potential therapeutic direction warranting further experimental validation.

PMID:
42898294
Bibliographic data and abstract were imported from PubMed on 20 Oct 2026.

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