Expression of histone acetyltransferase P300 in hepatocellular carcinoma tissue and its clinical significance

doi:10.3760/cma.j.cn371439-20200608-00079

Abstract

Abstract:

Objective To investigate the expression and clinical significance of histone acetyltransferase P300 in hepatocellular carcinoma. Methods From January 2013 to December 2017, surgical specimens of 100 patients with hepatocellular carcinoma were collected from the Department of General Surgery of Sichuan Mianyang 404 Hospital. The expressions of P300, CD90, alpha fetoprotein (AFP), Ki-67 and CD34 in hepatocellular carcinoma tissue were detected. At the same time, 42 hepatic hemangioma specimens and 56 liver tissue specimens with moderate to severe liver cirrhosis were collected, and the positive expression rate of P300 in tissues was detected. The correlations between the expression of P300 and clinicopathological features and prognosis of patients with hepatocellular carcinoma were analyzed. Results The positive expression rates of P300 in normal liver tissue, liver cirrhosis tissue and hepatocellular carcinoma tissue increased gradually, which were 11.9% (5/42), 32.1% (18/56) and 57.0% (57/100) respectively, with a statistically significant difference (χ²=27.192, P<0.001). Tumor grade (χ²=9.337, P=0.009), T stage (χ²=8.794, P=0.032), clinical TNM stage (χ²=6.121, P=0.013), AFP (χ²=11.040, P=0.001), CD90 (χ²=9.903, P=0.002), CD34 (χ²=4.066, P=0.044) significantly affected the expression of P300. Spearman rank correlation analysis showed that the abnormal expression of P300 was positively correlated with the expression of AFP (r=0.335, P=0.001), CD90 (r=0.328, P=0.002) and CD34 (r=0.264, P=0.047), but had no significant correlation with the expression of Ki-67 (P>0.05). Survival analysis showed that the 5-year survival rate of patients with P300 positive expression was 17.6%, and that of patients with P300 negative expression was 62.5%, and there was a statistically significant difference (χ²=10.596, P<0.001). Cox multivariate analysis showed that P300 positive expression (RR=2.554, 95%CI: 1.261-4.502, P=0.009), CD90 positive expression (RR=3.574, 95%CI: 1.021-11.980, P=0.030) and TNM Ⅱ-Ⅳ stage (RR=0.332, 95%CI: 0.105-0.596, P=0.002) were independent risk factors for poor prognosis of patients with hepatocellular carcinoma. Conclusion The positive expression of P300 is closely related to the occurrence of hepatocellular carcinoma and can be used as an independent factor to judge the poor prognosis of patients with hepatocellular carcinoma.

Key words: Liver neoplasms, Prognosis, Histone acetyltransferase P300

Han Baojun. Expression of histone acetyltransferase P300 in hepatocellular carcinoma tissue and its clinical significance[J]. Journal of International Oncology, 2021, 48(7): 415-419.

Figures/Tables 5

References 14

[1]	Qiu WQ, Shi JF, Guo LW, et al. Medical expenditure for liver can-cer in urban China: a 10-year multicenter retrospective survey (2002-2011)[J]. J Cancer Res Ther, 2018, 14(9):163-170. DOI: 10.4103/jcrt.JCRT_709_16. doi: 10.4103/jcrt.JCRT_709_16
[2]	Zuo MX, Huang JH. The history of interventional therapy for liver cancer in China[J]. Journal of Interventional Medicine, 2018, 1(2):70-76. DOI: 10.19779/j.cnki.2096-3602.2018.02.02.
[3]	Zhang Q, Lou Y, Bai XL, et al. Immunometabolism: a novel perspective of liver cancer microenvironment and its influence on tumor progression[J]. World J Gastroenterol, 2018, 24(31):3500-3512. DOI: 10.3748/wjg.v24.i31.3500. doi: 10.3748/wjg.v24.i31.3500
[4]	梁宗英, 侯继申, 张乐, 等. 调亡抑制基因Survivin和乙酰基转移酶p300在食管癌组织中的表达以及临床意义[J]. 中国当代医药, 2019, 26(23):43-46. DOI: 10.3969/j.issn.1674-4721.2019.23.014.
[5]	Yamashita T, Honda M, Nakamoto Y, et al. Discrete nature of EpCAM⁺ and CD90⁺ cancer stem cells in human hepatocellular carcinoma[J]. Hepatology, 2013, 57(4):1484-1497. DOI: 10.1002/hep.26168. doi: 10.1002/hep.26168 pmid: 23174907
[6]	Vinogradov S, Wei X. Cancer stem cells and drug resistance: the potential of nanomedicine[J]. Nanomedicine (Lond), 2012, 7(4):597-615. DOI: 10.2217/nnm.12.22. doi: 10.2217/nnm.12.22
[7]	Li HM. Microcirculation of liver cancer, microenvironment of liver regeneration, and the strategy of Chinese medicine[J]. Chin J Integr Med, 2016, 22(3):163-167. DOI: 10.1007/s11655-016-2460-y. doi: 10.1007/s11655-016-2460-y
[8]	杨宇石, 石玉, 郑美娟, 等. 乳腺癌中乙酰化转移酶P300和H3K56乙酰化蛋白表达与新辅助化疗及临床病理特征的相关性[J]. 临床与实验病理学杂志, 2018, 34(7):747-751. DOI: 10.13315/j.cnki.cjcep.2018.07.009.
[9]	Liu Y, Mayo MW, Nagji AS, et al. BRMS1 suppresses lung cancer metastases through an E3 ligase function on histone acetyltransferase p300[J]. Cancer Res, 2013, 73(4):1308-1317. DOI: 10.1158/0008-5472.CAN-12-2489. doi: 10.1158/0008-5472.CAN-12-2489
[10]	Yokomizo C, Yamaguchi K, Itoh Y, et al. High expression of p300 in HCC predicts shortened overall survival in association with enhanced epithelial mesenchymal transition of HCC cells[J]. Cancer Lett, 2011, 310(2):140-147. DOI: 10.1016/j.canlet.2011.06.030. doi: 10.1016/j.canlet.2011.06.030 pmid: 21764211
[11]	Yamashita T, Ji J, Budhu A, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features[J]. Gastroenterology, 2009, 136(3):1012-1024. DOI: 10.1053/j.gastro.2008.12.004. doi: 10.1053/j.gastro.2008.12.004 pmid: 19150350
[12]	Chen Z, Li W, Qiu F, et al. Aspirin cooperates with p300 to activate the acetylation of H3K9 and promote FasL-mediated apoptosis of cancer stem-like cells in colorectal cancer[J]. Theranostics, 2018, 8(16):4447-4461. DOI: 10.7150/thno.24284. doi: 10.7150/thno.24284
[13]	Yang ZF, Ngai P, Ho DW, et al. Identification of local and circula-ting cancer stem cells in human liver cancer[J]. Hepatology, 2008, 47(3):919-928. DOI: 10.1002/hep.22082. doi: 10.1002/hep.22082
[14]	Nielsen JS, Mcnagny KM. Novel functions of the CD34 family[J]. J Cell Sci, 2008, 121(Pt22):3683-3692. DOI: 10.1242/jcs.037507. doi: 10.1242/jcs.037507

指标	β值	SE值	Wald值	RR值	95%CI	P值
P300表达(阳性/阴性)	0.869	0.326	7.133	2.554	1.261~4.502	0.009
CD90表达(阳性/阴性)	1.273	0.586	4.745	3.574	1.021~11.980	0.030
AFP表达(阳性/阴性)	0.260	0.268	1.112	1.310	0.769~1.898	0.300
Ki-67表达(阳性/阴性)	0.176	0.317	0.290	1.180	0.645~2.179	0.633
肿瘤分级(1~2级/3级)	-0.599	0.350	2.939	0.549	0.277~1.090	0.086
TNM分期(Ⅰ期/Ⅱ~Ⅳ期)	-1.570	0.188	77.635	0.332	0.105~0.596	0.002
T分期(T_1-2期/T_3-4期)	-0.454	0.282	2.597	0.639	0.368~1.125	0.107

[1]	Qian Xiaotao, Shi Ziyi, Hu Ge, Wu Xiaowei. Efficacy of consolidation chemotherapy after radical radiotherapy and chemotherapy for stage Ⅲ-ⅣA esophageal squamous cell carcinoma： a real-world clinical study [J]. Journal of International Oncology, 2024, 51(6): 326-331.
[2]	Yang Mi, Bie Jun, Zhang Jiayong, Deng Jiaxiu, Tang Zuge, Lu Jun. Analysis of the efficacy and prognosis of neoadjuvant therapy for locally advanced resectable esophageal cancer [J]. Journal of International Oncology, 2024, 51(6): 332-337.
[3]	Chen Hongjian, Zhang Suqing. Study on the relationship between serum miR-24-3p， H2AFX and clinical pathological features and postoperative recurrence in liver cancer patients [J]. Journal of International Oncology, 2024, 51(6): 344-349.
[4]	Fan Zhipeng, Yu Jing, Hu Jing, Liao Zhengkai, Xu Yu, Ouyang Wen, Xie Conghua. Predictive value of changes in inflammatory markers for prognosis in patients with advanced non-small cell lung cancer treated with the first-line immunotherapy plus chemotherapy [J]. Journal of International Oncology, 2024, 51(5): 257-266.
[5]	Yang Lin, Lu Ning, Wen Hua, Zhang Mingxin, Zhu Lin. Study on the clinical relationship between inflammatory burden index and gastric cancer [J]. Journal of International Oncology, 2024, 51(5): 274-279.
[6]	Liu Pingping, He Xuefang, Zhang Yi, Yang Xu, Zhang Shanshan, Ji Yifei. Risk factors of postoperative recurrence in patients with primary brain glioma and prediction model construction [J]. Journal of International Oncology, 2024, 51(4): 193-197.
[7]	Wan Fang, Yang Gang, Li Rui, Wan Qijing. Expression levels and clinical significance of serum miR-497 and miR-383 in patients with esophageal cancer [J]. Journal of International Oncology, 2024, 51(4): 204-209.
[8]	Yao Yixin, Shen Yulin. Predictive value of serum SOCS3 and TXNIP levels for the prognosis of patients with hepatocellular carcinoma treated with TACE [J]. Journal of International Oncology, 2024, 51(4): 217-222.
[9]	Sun Weiwei, Yao Xuemin, Wang Pengjian, Wang Jing, Jia Jinghao. Exploration of prognostic factors and nomogram construction for advanced non-small cell lung cancer treated with immunotherapy based on hematologic indexes [J]. Journal of International Oncology, 2024, 51(3): 143-150.
[10]	Liu Yulan, Jing Haiyan, Sun Jing, Song Wei, Sha Dan. Advances in predicting efficacy and prognostic markers of immunotherapy for gastric cancer [J]. Journal of International Oncology, 2024, 51(3): 175-180.
[11]	Peng Qin, Cai Yuting, Wang Wei. Advances on KPNA2 in liver cancer [J]. Journal of International Oncology, 2024, 51(3): 181-185.
[12]	Sun Guobao, Yang Qian, Zhuang Qingchun, Gao Binbin, Sun Xiaogang, Song Wei, Sha Dan. Research progress on the histopathological growth patterns of colorectal liver metastasis [J]. Journal of International Oncology, 2024, 51(2): 114-118.
[13]	Chen Boguang, Wang Sugui, Zhang Yongjie. Role of serum cholinesterase and inflammatory markers in the prognosis of stage ⅠA -ⅢA breast cancer [J]. Journal of International Oncology, 2024, 51(2): 73-82.
[14]	Jin Xudong, Chen Zhongjian, Mao Weimin. Research progress on the role of MTAP in malignant mesothelioma [J]. Journal of International Oncology, 2024, 51(2): 99-104.
[15]	Huang Zhen, Chen Yongshun. Research progress of circulating tumor DNA in the diagnosis and treatment of hepatocellular carcinoma [J]. Journal of International Oncology, 2024, 51(1): 59-64.