Rho GTPase-related prognostic signature for esophageal squamous cell carcinoma identifies CTTN as a candidate adverse prognostic marker.

Authors

Hua Chen, Jun-Er Xu, Qiancheng Lin, Pingping Dong, Wangkai Xie, Xiangyang Xue, Xiaoming Lin

Published in

Molecular biology reports. Volume 53. Issue 1. Jun 27, 2026. Epub Jun 27, 2026.

Abstract

Rho GTPases orchestrate actin dynamics and tumor cell motility, but their prognostic relevance in esophageal squamous cell carcinoma (ESCC) remains unclear. We aimed to identify Rho GTPase-related differentially expressed genes (DEGs), build a prognostic model, evaluate important gene expression against clinicopathological features, and examine CTTN function in vitro.
Transcriptomic data from GSE53625 and TCGA-ESCC were used. Rho GTPase-linked DEGs from tumor-normal comparisons entered univariate Cox, LASSO, and multivariable Cox analyses to construct a risk-score model; immune infiltration and a nomogram were also evaluated. For CTTN, 60 paired ESCC tissues were examined by Western blot and immunohistochemistry, and 18 additional pairs by qPCR, with correlations to clinicopathological variables and survival. ESCC cell lines were used to test the effects of CTTN expression on migration, invasion, and proliferation.
We identified 107 Rho GTPase-related DEGs enriched in actin cytoskeleton-remodeling pathways. Five genes (RHOV, RHOA, PIK3R1, CTTN, ARHGEF37) formed a prognostic signature that separated patients into high-risk and low-risk groups with different outcomes and remained associated with outcome after adjustment for available clinicopathological variables. However, stage and nodal status differed between risk groups, indicating that the signature may partly capture aggressive clinicopathological features. High-risk tumors showed differences in inferred immune-cell abundance, including B-cell, NK-cell, mast-cell, and neutrophil populations. CTTN was consistently upregulated versus normal tissue, especially in advanced-stage and nodal-metastatic disease, and enhanced ESCC cell migration and invasion in vitro.
We developed an exploratory Rho GTPase-based prognostic model for ESCC and identified CTTN as a candidate adverse prognostic marker and functional contributor to ESCC cell migration and invasion. The model, immune-infiltration findings, nomogram, and CTTN-related mechanistic interpretations require further validation in larger prospective cohorts and additional experimental systems.

PMID:
42364031
Bibliographic data and abstract were imported from PubMed on 27 Jun 2026.

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