| dc.description.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. |
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