ABSTRACT
Objective: To investigate the value of transglutaminase 4 in diagnosis and prognosis prediction of prostate cancer. Methods: Transglutaminase 4 immunostaining was performed with paraffin sections from 159 prostate cancer patients receiving radical prostatectomy, and the staining results were divided into 4 levels: negative staining, weak staining, moderate staining, and strong staining. The clinical and pathological information of the patients were obtained by reviewing the medical records. The follow-up data were collected by reviewing medical records, prostate cancer database of our department, and telephoning the patients or their family members. Expression of transglutaminase 4 and clinical, prognosis data of patients were subjected to statistical analysis. Results: The expression of transglutaminase 4 in the prostatic cancer tissue was significantly higher than that in the adjacent normal tissue (P<0.001); and the expressions were significantly different in patients with different Gleason grades (P<0.001) and different prostate specific antigen levels(P=0.005). Univariate Cox regression analysis indicated that high transglutaminase 4 expression was a risk factor of biochemical recurrence of prostatic cancer (P=0.020), but multivariate Cox regression analysis did not support this finding (P=0.139). Conclusion: Transglutaminase 4 expression is increased in prostate cancer tissues, and the expression is stronger in malignant tissues with higher Gleason grade and prostate specific antigen level.
ABSTRACT
Transglutaminase 4 is a member of enzyme family that catalyzes calcium-dependent posttranslational modification of proteins. Although transglutaminase 4 has been shown to have prostate-restricted expression pattern, little is known about the biological function of transglutaminase 4 in human. To gain insight into its role in prostate, we analyzed the expression status of human transglutaminase 4 in benign prostate hyperplasia (BPH) and prostate cancer (PCa). Unexpectedly, RT-PCR and nucleotide sequence analysis showed four alternative splicing variants of transglutaminase 4: transglutaminase 4-L, -M (-M1 and -M2) and -S. The difference between transglutaminase 4-M1 and -M2 is attributed to splicing sites, but not nucleotide size. The deduced amino acid sequences showed that transglutaminase 4-L, -M1 and -M2 have correct open reading frames, whereas transglutaminase 4-S has a truncated reading frame. RT-PCR analysis of clinical samples revealed that transglutaminase 4-M and -S were detected in all tested prostate tissue (80 BPH and 48 PCa). Interestingly, transglutaminase 4-L was found in 56% of BPH (45 out of 80) and only in 15% of PCa (7 out of 48). However, transglutaminase 4-L expression did not correlate with serum prostate-specific antigen (PSA) level, prostate volumes or PSA densities. These results will provide a clue to future investigation aiming at delineating physiological and pathological roles of human transglutaminase 4.
ABSTRACT
PURPOSE: Transglutaminase 4 (TGase 4) belongs to a family of enzymes that catalyzes the post-translational modification of proteins. In an attempt to establish its physiological function(s), the distribution of TGase 4 expression in the human eye was determined. METHODS: Ocular tissues obtained from five human whole eyeball postmortem (40(+1) weeks at gestation age, 2 months, 48, 66, 76 years) were stained with monoclonal antibodies against human TGase 4 using indirect immunohistochemical method. RESULTS: TGase 4 was found in the lacrimal glands, corneal epithelium and endothelium, conjunctival epithelium, lens epithelium, retina (inner segment of photoreceptor, external limiting membrane, outer plexiform layer, inner plexiform layer, retinal nerve fiber layer and internal limiting membrane), iris, ciliary muscle, ciliary nonpigmented epithelium and trabecular meshwork. Endothelium of blood vessels in all ocular tissues was also stained. Conjunctival stroma, choroid, anterior tenon's capsule were faintly stained. No evidence of immunostaining for TGase 4 was found in the corneal stroma, iris stroma, lens nucleus, ciliary process, sclera, extraocular muscle and optic nerve. CONCLUSIONS: The expression pattern of TGase 4 was different from those of other TGase isoforms in the human eye. This result may be helpful in further investigation of the role of TGase 4 in the ocular tissue.