Prognostic role of upregulated P300 expression in human cancers: A clinical study of synovial sarcoma and a meta‑analysis

Abstract

E1A binding protein p300 (P300) is a member of the histone acetyltransferase family of transcriptional co-activators, which are associated with various types of cancer. Numerous studies have evaluated the diagnostic value of P300, but their results are not consistent. Therefore, a clinical study and a meta-analysis were performed in the present study to investigate the prognostic value of P300 expression in human malignant neoplasms. Immunohistochemical (IHC) analysis was used to assess P300 expression in 43 paraffin-embedded primary synovial sarcoma (SS) samples. For the meta-analysis, eligible studies published until January 21, 2018 were identified by searching the PubMed, EMBASE and Web of Science databases. The IHC analysis indicated a high P300 expression rate in 33.3% (10/30) of biphasic SS (BSSs) and in 60% (6/10) of monophasic fibrous SS tissues. In BSS, the expression rate was significantly higher in the epithelial component (80.0%, 24/30) than that in the spindle-cell component (30.0%, 9/30; P<0.05). The meta-analysis indicated that high expression of P300 was associated with poor overall survival (OS) in digestive system malignant neoplasms (HR=1.54, 95% CI: 1.20-2.23), as well as with poor progression-free survival, recurrence-free survival and disease-free survival combined (HR=1.84, 95% CI: 1.36-2.47). Analysis of subgroups by ethnicity demonstrated that high expression of P300 was associated with poor OS in Asians (HR=1.72, 95% CI: 1.20-2.47) but favourable OS in Caucasians (HR=0.59, 95% CI: 0.47-0.73). Furthermore, high expression of P300 was associated with clinical stage [Relative Risk (RR)=1.30, 95% CI: 1.07-1.58], lymph node metastasis (RR=1.30, 95% CI: 1.03-1.64) and depth of invasion (RR=1.31, 95% CI: 1.07-1.60). P300 expression may therefore be a useful biomarker for predicting patient prognosis in various types of human cancer.

Novel fusion genes in spindle cell rhabdomyosarcoma: The spectrum broadens

“…It interacts with MDM2 to regulate the turnover of p53, an important tumor suppressor 22 . The prognostic value of p300 overexpression is unclear; however, it has been associated with unfavorable outcomes in patients with synovial sarcoma, and breast and laryngeal carcinomas 23 . Histologically and immunohistochemically, there were no significant differences between our case and those reported with VGLL2 ‐related fusions.…”

Targeting pioneer transcription factor Ascl1 to promote optic nerve regeneration

“…In the paradigm of axon regeneration, it is known that many RAGs are either proto-oncogenes, or participate in signaling pathways initially discovered in tumorous cells, which may include but not limit to the abnormal expression of p300, HDACs, PTEN, and Klf family TFs found in a myriad of different types of cancers (Liu et al, 2019;Milella et al, 2015;Tetreault et al, 2013). Also, the misfunction of PI3K/Akt signaling is implicated in a variety of cancers (Janku et al, 2018).…”

WNT/β-Catenin Pathway in Soft Tissue Sarcomas: New Therapeutic Opportunities?

“…While in many cancers, the aberrant activation of the canonical WNT pathway is due to mutations in this gene or other important components of the pathway such as APC [ 21 , 112 ], in the context of STS, few CTNNB1 mutations have been described. It seems that other mechanisms such as autocrine loop activation [ 81 ], fusion proteins [ 59 , 93 , 94 ], or genomic alterations [ 60 , 63 ] have an important role in the upregulation of the WNT canonical pathway, leading to nuclear β-catenin accumulation and activation of its transcriptional program. Even so, most desmoid tumors (fibrous mesenchymal tumors, including FS) harbor somatic missense mutations in codons 41 (T41A) or 45 (S45F) of exon 3 sequence, which encodes the regulatory degradation targeting box of β-catenin.…”

“…In a study of 43 SS tumor samples, Liu et al (2019) found high p300 protein expression in SS, being more prevalent in monophasic SS. Although high p300 expression has been associated with poor overall survival (OS), progression-free survival, and recurrence-free survival in various types of human cancer, such as digestive system malignant neoplasms, the prognostic value of p300 expression has not been proved yet in SS [ 94 ].…”