Extracellular matrix stiffness in oral squamous cell carcinoma: a systematic review and meta-analysis of associations with tumor progression and prognosis
- 1Federal University of Rio Grande do Sul
Abstract
ObjectiveTo critically evaluate the influence of extracellular matrix stiffness on tumor progression, prognosis, and clinical implications in patients with oral squamous cell carcinoma.
DesignThis systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and the protocol was registered in PROSPERO (CRD420251156429). Five databases (PubMed, Scopus, Embase, Web of Science, and OATD) were searched without restrictions on publication year or language. Human studies that evaluated extracellular matrix stiffness in oral squamous cell carcinoma, either as an assessment method or as a prognostic factor, were included; in vitro and animal studies were excluded.
ResultsEight human studies involving 436 patients were included. Elastography was the most frequent measurement method, employed in four studies. Mean tumor thickness was reported in three studies and ranged from 3.0 to 4.4 mm. Extracellular matrix stiffness was expressed in various units (e.g., 37.7 gf, 23.5 kPa) and was consistently higher in tumor tissue than in normal mucosa in all studies. Three studies demonstrated a significant positive correlation between stiffness and tumor thickness. One study identified predictive cut-off values for lymph node metastasis and reported that high matrix stiffness was an independent predictor of worse overall survival (HR = 4.022; 95% CI: 1.294-12.495; p = 0.016) and recurrence-free survival (HR = 5.680; 95% CI: 1.146-28.143; p = 0.033). A meta-analysis of five studies (307 patients) showed a significantly higher standardized stiffness in oral squamous cell carcinoma compared with normal oral mucosa (standardized mean difference = 5.28; 95% CI: 2.61-7.94; p < 0.001), with substantial heterogeneity (I{superscript 2} = 98.6%).
ConclusionsExtracellular matrix stiffness is elevated in oral squamous cell carcinoma and is associated with greater tumor thickness, lymph node metastasis and, in one study, worse survival. These findings support extracellular matrix stiffness as a potential biomechanical marker, pending further validation in standardized prospective studies.
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BibTeX
@misc{lima2026extracellular,
title = {{Extracellular matrix stiffness in oral squamous cell carcinoma: a systematic review and meta-analysis of associations with tumor progression and prognosis}},
author = {I. F. P. Lima and A. C. Toebe Silva and A. J. Engler and L. d. S. Bittencourt and M. L. Lamers},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.26363990},
url = {https://www.medrxiv.org/content/10.64898/2026.09.28.26363990v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Extracellular matrix stiffness in oral squamous cell carcinoma: a systematic review and meta-analysis of associations with tumor progression and prognosis
AU - I. F. P. Lima
AU - A. C. Toebe Silva
AU - A. J. Engler
AU - L. d. S. Bittencourt
AU - M. L. Lamers
PY - 2026
DA - 2026/09/28
PB - medRxiv
DO - 10.64898/2026.09.28.26363990
UR - https://www.medrxiv.org/content/10.64898/2026.09.28.26363990v1
AB - ObjectiveTo critically evaluate the influence of extracellular matrix stiffness on tumor progression, prognosis, and clinical implications in patients with oral squamous cell carcinoma. DesignThis systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and the protocol was registered in PROSPERO (CRD420251156429). Five databases (PubMed, Scopus, Embase, Web of Science, and OATD) were searched without restrictions on publication year or language. Human studies that evaluated extracellular matrix stiffness in oral squamous cell carcinoma, either as an assessment method or as a prognostic factor, were included; in vitro and animal studies were excluded. ResultsEight human studies involving 436 patients were included. Elastography was the most frequent measurement method, employed in four studies. Mean tumor thickness was reported in three studies and ranged from 3.0 to 4.4 mm. Extracellular matrix stiffness was expressed in various units (e.g., 37.7 gf, 23.5 kPa) and was consistently higher in tumor tissue than in normal mucosa in all studies. Three studies demonstrated a significant positive correlation between stiffness and tumor thickness. One study identified predictive cut-off values for lymph node metastasis and reported that high matrix stiffness was an independent predictor of worse overall survival (HR = 4.022; 95% CI: 1.294-12.495; p = 0.016) and recurrence-free survival (HR = 5.680; 95% CI: 1.146-28.143; p = 0.033). A meta-analysis of five studies (307 patients) showed a significantly higher standardized stiffness in oral squamous cell carcinoma compared with normal oral mucosa (standardized mean difference = 5.28; 95% CI: 2.61-7.94; p < 0.001), with substantial heterogeneity (I{superscript 2} = 98.6%). ConclusionsExtracellular matrix stiffness is elevated in oral squamous cell carcinoma and is associated with greater tumor thickness, lymph node metastasis and, in one study, worse survival. These findings support extracellular matrix stiffness as a potential biomechanical marker, pending further validation in standardized prospective studies.
ER -