Transketolase Like 1 Expression Alterations In Prostate Cancer Tumorigenesis

Abstract

Deregulated cellular energetics has been recently proposed as an emerging hallmark of cancer. Cancer cells, in aerobic conditions, show an increased glucose uptake and lactate secretion in order to support their rapid proliferation. Transketolase like 1 (TKTL1) helps cancer cells meet their energy demands and combat oxidative stress and has been reported to be over-expressed in several human tumours including urothelial carcinomas, ovarial, colon and breast carcinoma. However, there is few data on TKTL1 in prostatic adenocarcinoma (PCa). Prostate cancer is the second most common cancer among men worldwide, and an urgent need exists for new diagnostic, prognostic and predictive tests. In order to investigate TKTL1 expression in PCa in different stages of progression we included 124 tissue samples. Tumour tissue of 53 patients who underwent prostatectomy, as well as corresponding adjacent non-neoplastic prostate tissue were analyzed. A total of 45 patients with metastatic prostate cancer were also included. 26 patients were included as controls. From the TMA slides, we evaluated the expression of the TKTL1 protein, using the Hscore (score range from 0 until 300) by immunohistochemical analysis. Due to artefacts or insufficient data, tissues from 24 patients were excluded from the study, leaving a total of number of 100 eligible patients. TKTL1 expression was significantly higher in tumour tissue in comparison with normal tissue (243.13 (187.04, 295) compared to 100 (57.5, 105), p<0.001). The TKTL1 protein expression pattern ranges from a low level in benign prostatic tissue (100 (57.5, 105) to moderate expression in non-metastatic PCa (200 (172.19-254.38) and metastatic PCa (300 (222.50-300). In the group of patients with metastatic prostate cancer no difference was found between TKTL1 expressions in tissues from hormone-sensitive or hormone-refractory prostate cancer (p=0.9015). An upregulation of TKTL1 in prostate cancer was evident, multiple clinicopathological parameters showed a significant relationship with high or low levels of TKTL1: M-stage (p=0.0023), T-stage (p=0.0027), Nstage (p=0.0257) and Gleason score (p=0.0075).A significant difference was found between peritumoral (non-malignant) prostate tissue and benign tissue, a higher TKTL1 expression being present in peritumoral tissue (135.42 (100-195.16) compared with 100 (57.5-105), p=0.006). TKTL1 expression reflects an intrinsic process of glucose metabolism reprogramming and therefore is not detectable through the diagnostic Gleason score grading system, since this classification is only based on morphological alterations. Both group tissues were classified as non-malignant, in spite of signs of tumorigenesis process being seen in the non-malignant peritumoral tissue.TKTL1 protein is still not explored enough and has not yet reached its final potential. This enzyme could be a potential candidate as an adjunct test for prostate cancer or as a targeted inhibitor of tumour growth.