摘要
背景肝细胞癌(hepatocellular carcinoma,HCC),是世界上第六大常见恶性肿瘤和第三大癌症死亡原因,在过去的30年里,全世界肝癌患者的发病率从每10万人1.6人上升到4.6人.广西是我国HCC的高发区,其死亡率居广西肿瘤死因谱首位,约占全部恶性肿瘤的40%.因此探讨色素框同源物2(chromobox homolog 2,CBX2)在肝细胞癌免疫中的作用,将为HCC治疗提供潜在的价值.目的探讨CBX2基因在HCC组织中的表达及其免疫和预后意义.方法采用组织微阵列和免疫组织化学方法检测75例HCC及其对应癌旁非肿瘤组织中的CBX2的表达,分析CBX2与HCC的临床病理特征以及患者生存预后之间的关系.探讨CBX2与免疫调节因子之间的关系,并通过GO和KEGG通路富集分析确定CBX2与免疫事件有关.使用COX回归模型开发多基因风险预测模型,由此产生的风险评分是一个独立的预测因子.我们使用接受者操作特性(receiver operating characteristic,ROC)曲线方法评估风险评分的预测准确性.最后,构建了带有校准曲线的预后诺模图,以预测个体的3年和5年生存概率.结果CBX2在HCC组织中的阳性表达为66.7%(50/75),明显高于癌旁非肿瘤组织25.3%(19/75),差异有统计学意义(P<0.01).结合临床病理学特征分析发现,CBX2的表达与HCC患者的TNM分期和AFP具有相关性(P<0.05).进一步生存分析发现,CBX2阳性组患者的生存时间明显高于阴性组,提示CBX2阴性表达可能与HCC患者的不良预后相关;CBX2表达与辅助型T细胞2的浸润水平呈正相关;我们确定了CBX2与10个免疫抑制因子和23个免疫刺激因子之间的关系,相关的GO和KEGG通路富集分析表明CBX2与介导的免疫事件相关.结论CBX2阳性表达是HCC患者的预后危险因素;CBX2可能是HCC的潜在免疫预后标志物.
BACKGROUND The number of cases of hepatocellular carcinoma(HCC),the sixth most common malignancy and the third leading cause of cancer death worldwide,has risen from 1.6 to 4.6 per 100000 people worldwide over the past 30 years.Guangxi has a high incidence of HCC in China,and its death rate ranks first in the spectrum of causes of tumor death in Guangxi,accounting for about 40% of all deaths from malignant tumors.Exploring the role of chromobox homolog 2(CBX2)in HCC immunity will provide potential value for the treatment of this malignancy.AIM To investigate the expression of CBX2 and analyze its immunological and prognostic significance in HCC.METHODS The expression of CBX2 in 75 cases of HCC and matched non-tumor tissues was detected by tissue microarray and immunohistochemistry.The relationship of CBX2 expression with the clinicopathologic features of HCC and survival prognosis was analyzed.Then,the differential expression of CBX2 between HCC and normal tissues was verified in The Cancer Genomic Atlas(TCGA).Next,we explored the association between CBX2 expression and immunocyte infiltration,determined the relationship between CBX2 expression and immunosuppressors and immunostimulators,and identified the immune events that CBX2 was involved in through relevant GO and KEGG pathway enrichment analyses.A multi-gene risk prediction model was developed using a COX regression model,thereby generating a risk score that is an independent predictor of survival prognosis.ROC analysis was performed to assess the predictive accuracy of the risk score.Finally,a prognostic model with a calibration curve was constructed to predict the patients’survival probability at 3 and 5 years.RESULTS The positive expression of CBX2 in HCC tissue was 66.7%(50/75),which was significantly higher than that in matched non-tumor tissues(25.3%(19/75);P<0.01).The expression of CBX2 was associated with TNM stage and AFP status(P<0.05).The survival time of patients in the CBX2 positive group was significantly lower than that of the CBX2 negative
作者
宋鑫
王添贤
朱小年
谭盛葵
Xin Song;Tian-Xian Wang;Xiao-Nian Zhu;Sheng-Kui Tan(School of Public Health,Guilin Medical University,Guilin 541199,Guangxi Zhuang Autonomous Region,China)
出处
《世界华人消化杂志》
CAS
2021年第19期1118-1129,共12页
World Chinese Journal of Digestology
基金
国家自然基金《免疫相关蛋白CMTM6在肝细胞癌恶性进展中的作用及机制》,No.82060621.
关键词
肝细胞癌
CBX2
预后
免疫浸润
Hepatocellular carcinoma
CBX2
Prognosis
Immune infiltration
