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Integrative genomics and experimental validation identify a mechanosensitive gene signature associated with colorectal cancer liver metastasis

Year: 2026

Type: article

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.

Source: iScience

DOI: 10.1016/j.isci.2026.117926

Authors: Tianxue Yang, Ye Yuan, Xue Li, Jiaqi Wang, Chenyao Li, Ziran Xu

Institutions: Essen University Hospital, First Hospital of Jilin University, Stiftung Universitätsmedizin Essen, Chinese People's Liberation Army

Language: English

Topic: Cellular Mechanics and Interactions

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,240