The prognostic capacities of CBP and p300 in locally advanced rectal cancer
Rühlmann, Felix ; Windhof-Jaidhauser, Indra M ; Menze, Cornelius ; Beißbarth, Tim ; Bohnenberger, Hanibal ; Ghadimi, Michael ; Dango, Sebastian
Citable Link (URL):http://resolver.sub.uni-goettingen.de/purl?gs-1/17044
Abstract Background CREB-binding protein (CBP) and p300 represent histone acetyltransferases (HATs) and transcriptional coactivators that play essential roles in tumour initiation and progression. Both proteins are generally thought to function as tumour suppressors, although their distinct roles in colorectal cancer (CRC) remain inconsistent and ambiguous. Thus, we analysed the expression of these two HATs in human tissue samples from patients with locally advanced rectal cancer via immunohistochemistry and evaluated their potential impacts on future CRC diagnosis and treatment. Methods In our analysis, we included ninety-three (n = 93) patients diagnosed with adenocarcinoma in the upper third of the rectum. None of the patients received preoperative chemoradiotherapy, but the patients did undergo primary resection of the tumour within the phase II GAST-05 trial. By using H-scores, the expression of both proteins was visualised via immunohistochemistry in resected specimens from the patients. CBP and p300 expression were correlated with clinical and follow-up data. Results Our analysis showed that high expression of CBP was significantly associated with prolonged cancer-specific survival (CSS; p = 0.002). In univariate analysis, CBP was an independent prognostic parameter for CSS (p = 0.042). High nuclear CBP expression was observed in two-thirds of patients. In contrast, we could not find any significant correlation between the expression of p300 and cancer-specific survival in this cohort of patients (p = 0.09). We did not observe any cooperation between CBP and p300 in our analysis. Conclusions High expression of CBP was significantly associated with improved oncological outcomes. This finding could help to stratify patients in the future for CRC treatment. Histone deacetylase (HDAC) inhibitors are increasingly playing a role in oncological treatment and could additionally become therapeutic options in CRC. Our findings need to be further evaluated and verified in future clinical analyses.