Toll-Like Receptor 4 and Matrix Metalloproteases 11 and 13 as Predictors of Tumor Recurrence and Survival in Stage II Colorectal Cancer
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Current clinical-pathologic stratification factors do not allow clear identification of high-risk stage II colorectal cancer (CRC) patients. Therefore, the identification of additional prognostic markers is desirable. Toll-like receptor (TLR)-4 is activated during tumorigenesis and matrix metalloproteases (MMPs) are involved in invasion and metastasis. We aimed to evaluate the expression and clinical relevance of TLR4, MMP11 and MMP13 for patients with stage II CRC. Immunohistochemistry was used to study the expression of TLR4, MMP11 and MMP13 in 96 patients with stage II CRC. We measured the global expression and the expression by different cell types (tumor cells, cancer-associated fibroblasts (CAFs) and mononuclear inflammatory cells (MICs)). The potential relationship between expressions of factors and different prognostic variables were evaluated. Our results show significant relationships between either TLR4 expression by tumor cells and MMP11 expression by CAFs and high risk of tumor recurrence. In addition, the concurrence of age ≥ 75 years and the non-expression of MMP11 by CAFs identify a subgroup of patients with a good prognosis. Our results show that TLR4 expression by tumor cells and MMP11 expression by CAFs may to improve the identification of patients with stage II CRC with a high-risk of relapse.
KeywordsPrognostic factor Stage II colorectal cancer Survival TLR4 MMP11 MMP13
NE, JFC and FV designed the study, analyzed and interpreted data. NE, JFC, SC, LOG, JLGM and AA collected data, carried out experiments, analyzed data and generated the figures. All authors were involved in writing the paper and had final approval of the submitted and published version. FV accepts full responsibility for the work and/or the conduct of the study, had access to the data, and oversaw the decision to publish.
This work was supported by grant from the Consejería de Economía y Empleo del Principado de Asturias (GRUPIN14–116) S.C. was recipient of a predoctoral fellowship financed by the Gobierno del Principado de Asturias “Severo Ochoa” PhD Program (BP14–128).
Compliance with Ethical Standards
The study is adhered to National regulations, and was approved by the Fundación Hospital de Jove Ethics and Investigation Committee.
Conflict of Interest
The authors declare that they have no conflicts of interest.
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