肝细胞癌基因组及转录组特征与免疫相关性

doi:10.3760/cma.j.cn371439-20220221-00056

摘要/Abstract

摘要：

肝细胞癌是国内常见的恶性肿瘤,其全球发病率持续上升且死亡率高。肝脏基因组的畸变会导致细胞恶性转化以及肝细胞癌的发生,这也是潜在的治疗靶点。肝细胞癌微环境中不同免疫细胞的成分如肿瘤相关巨噬细胞、中性粒细胞可以促进肿瘤进展,细胞毒性T淋巴细胞可破坏肿瘤细胞。细胞中不同的特征基因表型可以促进或抑制免疫耐受,这能够解释肝细胞癌患者对免疫治疗敏感或耐药的潜在原因,为探索新的免疫治疗靶点提供参考。进一步加深对肝细胞癌中基因组与转录组特征的认知以及认识其与免疫治疗的相关性,可为临床诊治提供新思路。

关键词: 癌,肝细胞, 肝硬化, 免疫治疗

Abstract:

Hepatocellular carcinoma is a common malignant tumor in China, and its global incidence continues to rise and the mortality rate is high. Aberrations in the liver genome lead to malignant transformation of cells and the development of hepatocellular carcinoma, which are also potential therapeutic targets. Different immune cell components in the hepatocellular carcinoma microenvironment, such as tumor-associated macrophages, neutrophils, can promote tumor progression, and cytotoxic T lymphocytes can destroy tumor cells. Different characteristic gene phenotypes in cells can promote or inhibit immune tolerance, which can explain the potential reasons for the sensitivity or resistance of hepatocellular carcinoma patients to immunotherapy, and provide a reference for the exploration of new immunotherapy targets. Further deepening the understanding of the genomic and transcriptomic features in hepatocellular carcinoma and its correlation with immunotherapy can provide new ideas for clinical diagnosis and treatment.

Key words: Carcinoma, hepatocellular, Liver cirrhosis, Immunotherapy

孙笑可, 杨宇. 肝细胞癌基因组及转录组特征与免疫相关性[J]. 国际肿瘤学杂志, 2022, 49(5): 302-306.

Sun Xiaoke, Yang Yu. Correlations between genomic and transcriptome characteristics and immune in hepatocellular carcinoma[J]. Journal of International Oncology, 2022, 49(5): 302-306.

图/表 1

参考文献 36

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基因	基因组改变	占比	生物学途径
TERT^[12⇓-14]	启动子突变	50%~60%	端粒维持
TERT^[13-14]	扩增	6%	端粒维持
TERT^[13-14]	易位	3%	端粒维持
TP53^[13-14]	失活突变	15%~40%	细胞周期控制
CDKN2A^[14]	失活突变	2%~9%	细胞周期控制
CCND1^[14]	扩增	7%	细胞周期控制
CTNNB1^[12⇓-14]	激活突变	10%~35%	Wnt/β-连环蛋白途径
AXIN1^[13-14]	失活突变	5%~15%	Wnt/β-连环蛋白途径
FGF19^[13-14]	扩增	5%~10%	PI3K/AKT-mTOR途径
RPS6KA3^[13-14]	失活突变	2%~9%	PI3K/AKT-mTOR途径
VEGFA^[13-14]	扩增	4%	PI3K/AKT-mTOR途径
ARID1A^[12⇓-14]	失活突变	5%~17%	染色质重塑
ARID2^[13-14]	失活突变	3%~18%	染色质重塑
NFE2L2^[13-14]	激活突变	3%~6%	氧化应激途径
KEAP1^[13-14]	失活突变	2%~8%	氧化应激途径