Integrative genomics and experimental validation identify a mechanosensitive gene signature associated with colorectal cancer liver metastasis
Abstract
The mechanical tumor microenvironment critically influences colorectal cancer (CRC) progression and metastasis, yet the underlying molecular mediators remain poorly defined. By integrating single-cell transcriptomics, bulk RNA-seq, weighted gene co-expression network analysis, and 117 machine learning algorithms, we identified a six-gene mechanosensitive signature (SNX7, SDC1, CDCP1, PTGES, EMP2, and CALB2) associated with CRC liver metastasis. This signature demonstrated superior prognostic performance (mean C-index 0.68) across multiple independent cohorts compared to 74 published CRC signatures. Among these genes, SDC1 was consistently upregulated in CRC cells and tissues, and its expression was further induced by increased matrix stiffness in tunable hydrogel culture systems. These findings support a mechanosensitive gene signature with robust prognostic value and identify SDC1 as a stiffness-responsive candidate regulator, providing insights into the mechanobiological regulation of CRC metastasis.
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BibTeX
@article{yang2026integrative,
title = {{Integrative genomics and experimental validation identify a mechanosensitive gene signature associated with colorectal cancer liver metastasis}},
author = {Tianxue Yang and Ye Yuan and Xue Li and Jiaqi Wang and Chenyao Li and Ziran Xu},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117926},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03309-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrative genomics and experimental validation identify a mechanosensitive gene signature associated with colorectal cancer liver metastasis
AU - Tianxue Yang
AU - Ye Yuan
AU - Xue Li
AU - Jiaqi Wang
AU - Chenyao Li
AU - Ziran Xu
PY - 2026
DA - 2026/10/16
JO - iScience
DO - 10.1016/j.isci.2026.117926
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03309-2
AB - The mechanical tumor microenvironment critically influences colorectal cancer (CRC) progression and metastasis, yet the underlying molecular mediators remain poorly defined. By integrating single-cell transcriptomics, bulk RNA-seq, weighted gene co-expression network analysis, and 117 machine learning algorithms, we identified a six-gene mechanosensitive signature (SNX7, SDC1, CDCP1, PTGES, EMP2, and CALB2) associated with CRC liver metastasis. This signature demonstrated superior prognostic performance (mean C-index 0.68) across multiple independent cohorts compared to 74 published CRC signatures. Among these genes, SDC1 was consistently upregulated in CRC cells and tissues, and its expression was further induced by increased matrix stiffness in tunable hydrogel culture systems. These findings support a mechanosensitive gene signature with robust prognostic value and identify SDC1 as a stiffness-responsive candidate regulator, providing insights into the mechanobiological regulation of CRC metastasis.
SN - 2589-0042
ER -