The prognostic capacities of CBP and p300 in locally advanced rectal cancer

Abstract

BackgroundCREB-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.MethodsIn 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.ResultsOur 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.ConclusionsHigh 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.

Targeting Wnt/Beta-Catenin Signaling in HPV-Positive Head and Neck Squamous Cell Carcinoma

“…High CBP expression was linked to better survival times. Similar results on protein level were shown by Rühlmann et al [ 22 ] for patients with locally advanced rectal cancer. The mechanistic background behind the association of high CBP expression with better survival in HPV-positive HNSCC patients certainly warrants further elucidation.…”

Screening of a large Rubinstein–Taybi cohort identified many novel variants and emphasizes the importance of the CREBBP histone acetyltransferase domain

“…The p300 protein has many similar domains to CBP, including KIX, BRD, HAT, and the zinc finger domains (Arany, Sellers, Livingston, & Eckner, 1994; Bordoli et al, 2001; Rack et al, 2014; Raisner et al, 2018; Teufel, Freund, Bycroft, & Fersht, 2007; Zhang et al, 2018). p300 and CBP are distinct but related proteins that function as transcriptional co‐activators that are involved in multiple signal‐dependent transcription events (Chan & La Thangue, 2001; Ding, Yang, Zhao, & Guozhong Lv, 2017; Fauquier et al, 2018; Rühlmann et al, 2019).…”

Development and Validation of a Prognostic Signature Based on the Lysine Crotonylation Regulators in Head and Neck Squamous Cell Carcinoma

“…CREBBP and EP300 are widely recognized histone acetyltransferases and transcriptional coactivators that share approximately 60% homology and play vital roles in various cellular activities such as cell growth, differentiation, DNA repair, and apoptosis [32][33][34]. Notably, CREBBP was previously reported as a novel tumor suppressor, and CREBBP dysfunction was correlated with carcinogenesis and progression in several human malignancies [35,36]. Similarly, our findings also revealed that high CREBBP expression was associated with a favorable HNSCC prognosis, indicating that CREBBP might play a tumor-suppressive role in HNSCC.…”