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Prognostic role of tissue transglutaminase 2 in colon carcinoma

Abstract

Tissue transglutaminase 2 (TG2) is involved in many biological processes, from wound healing to neurodegeneration. Recently, there has been an increasing interest in this enzyme as a potential prognostic marker or therapy target in human neoplasms. The aim of this study was to analyze expression of TG2 messenger RNA (mRNA) and protein in colon cancer samples and to evaluate the potential value of TG2 as prognostic marker. We investigated not only expression level but also location of the protein in a series of human tumors. In silico analysis using the GSE39582 dataset showed that TG2 mRNA expression is associated with earlier relapse. The results of qPCR in our cohort showed TG2 mRNA to be up-regulated in 25 out of 70 samples (34 %). Kaplan-Meier plots and log-rank test showed that patients with high TG2 mRNA expression have significantly worse prognosis in terms of overall survival (OS) and a trend to earlier recurrence. Immunohistochemical staining of tumor sections for TG2 revealed stromal staining in 152 cases (88 %) and epithelial cell staining in 105 cases (62 %). In stage II patients, stromal expression showed a significant association with disease-free survival (DFS). In patients with metastatic disease, TG2 expression was also associated with poor prognosis. Cox multivariate analysis showed that TG2 expression in epithelial cells is significantly and independently associated with OS, together with node involvement and presence of metastasis. Stromal TG2 expression was associated with DFS. In summary, in non-metastatic colorectal cancer patients, stromal TG2 expression is significantly associated with DFS and epithelial TG2 expression with OS, independently of node involvement and metastasis.

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Acknowledgments

The authors acknowledge no conflict of interest for the elaboration of the present report.

Author information

Correspondence to María Jesús Fernández-Aceñero or J. Ignacio Casal.

Ethics declarations

This work is in accordance with National and International Ethical Standards and has been approved by the Ethical Committee of Hospital Clínico San Carlos and Fundación Jiménez Díaz.

Funding

ST was a recipient of the Juan de la Cierva program. IGP was supported by a contract S2010/BMD-2344/Colomics2 from the Comunidad de Madrid. This research was supported by grants BIO2012–31,023 and BIO2015–66,489-R from the MINECO and PRB2 (IPT13/0001-ISCIII-SGEFI/FEDER) from the Instituto de Salud Carlos III-FEDER.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

María Jesús Fernández-Aceñero and Sofía Torres contributed equally to this work.

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Fernández-Aceñero, M.J., Torres, S., Garcia-Palmero, I. et al. Prognostic role of tissue transglutaminase 2 in colon carcinoma. Virchows Arch 469, 611–619 (2016). https://doi.org/10.1007/s00428-016-2020-z

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Keywords

  • Transglutaminase 2
  • Colon carcinoma
  • Prognosis
  • mRNA
  • Metastasis