The p300/CBP associated factor: is frequently downregulated in intestinal-type gastric carcinoma and constitutes a biomarker for clinical outcome.

摘要

Objectives: To investigate the expression of P300/CBP-associated factor (PCAF) protein in intestinal type gastric cancer (ITGC); analyze the relationship between the expression of PCAF protein and the clinical pathological characteristics of patients; explore the effects of PCAF protein on biological behaviors of ITGC. Results: The expression of PCAF was markedly downregulated in GC cell lines and ITGC tissues. PCAF was able to suppress tumorigenicity of GC cells both in vitro and in vivo, including colony formation in soft agar and tumor formation in nude mice. PCAF could also inhibit GC cells entering S phase from G1 phase. Statistical analysis displayed a significant correlation in PCAF expression with the gastric wall invasion, tumor size, TNM stage, p21, pRb (p < 0.001) and PCNA (p < 0.01) in ITGC specimens. A reduced PCAF protein expression correlated significantly with a mutant type p53 protein expression (p < 0.01). Univariate analysis indicated that the patients demonstrating the high-PCAF/wild type p53 expression have a significantly (p < 0.0001) better overall survival (OS), while multivariate analysis indicated that the location, lymph node metastasis, PCAF/p53 (p < 0.0001), gastric wall invasion (p = 0.001) and PCNA (p = 0.018) are independently significant prognostic factors for OS. Methods: Immunohistochemistry was performed to evaluate the expression of PCAF in a large subset containing 406 ITGC samples. Eukaryotic expression plasmid pcDNA3.1/PCAF was constructed and transfected into the human gastric cancer cell line SGC-7901 and protein expression was detected by western blot. The proliferation and cell cycle of gastric cancer cells were evaluated by MTT assay and flow cytometry. Tumor growth in nude mice was used to access the tumorigenicity of gastric cancer cells. Apoptosis cells were detected by TUNEL staining. Conclusion: Reduced expression of PCAF plays an important role in the development of ITGC and correlates with a poor clinical outcome.