Overexpression of transglutaminase 4 and prostate cancer progression: a potential predictor of less favourable outcomes

Abstract

Transglutaminase 4 has been shown to enhance various biological properties of prostate cancer cells, e.g., cell-matrix adhesion, invasiveness and the epithelial-mesenchymal transition. The objectives of this study were to investigate the associations between transglutaminase 4 expression and the established features and biochemical recurrence of prostate cancer. Transglutaminase 4 immunostaining was performed on a tissue microarray. The expression of transglutaminase 4 was evaluated by a scoring method based on the intensity and extent of staining. The clinical and pathological information was obtained through a review of medical records. Follow-up data were obtained by consulting the hospital medical records and the prostate cancer database of our department and by contacting patients or family members. We then compared the transglutaminase 4 expression levels between the prostate cancer tissues and the paracarcinoma tissues and evaluated the correlation of transglutaminase 4 expression with the clinical parameters and biochemical recurrence of prostate cancer. Our results indicated that the transglutaminase 4 staining was significantly higher in tumour tissue than in paracarcinoma tissue (P<0.001) and was positively associated with higher Gleason score (P<0.001) and higher prostate-specific antigen level (P=0.005). Patients with transglutaminase 4 overexpression experienced shorter biochemical recurrence-free survival after surgery (P=0.042) in the univariate analysis but not in the multivariate analysis (P=0.139), which indicated that transglutaminase 4 may serve as a potential predictor of biochemical recurrence of prostate cancer.

Figure 1

Examples of TGM4 immunostaining in prostate cancer and normal tissues. (a) Lack of staining, paracarcinoma tissue; (b) weak staining, T2aN0 M0, Gleason score: 3+3; (c) moderate staining, T3aN0 M0, Gleason score: 3+4; (d) strong staining, T3bN0 M0, Gleason score: 5+5. TGM4, transglutaminase 4.

Figure 2

Influence of TGM4 expression on biochemical recurrence. Low score: IE scores 0–5, High score: IE scores 6–12. Adequate follow-up data were available for 117 patients; 52 patients experienced BCR, and BCR was not observed in 65 patients. BCR, biochemical recurrence; IE score, intensity score (I)×extent (E) score under ×200 visual field magnification; IHC, immunohistochemistry; RP, radical prostatectomy; PSA, prostate-specific antigen; TGM4, transglutaminase 4; TMA, tissue microarray.