研究动态
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细胞衰老相关基因在肝细胞癌预后、分子特征及免疫疗法方面的综合分析。

Comprehensive Analysis of Cellular Senescence-Related Genes in Prognosis, Molecular Characterization and Immunotherapy of Hepatocellular Carcinoma.

发表日期:2022 Dec 19
作者: Liang Sun, Zitao Liu, Ke Ning, Zhipeng Wu, Zhendong Chen, Zhengyi Wu, Xiangbao Yin
来源: BIOLOGICAL PROCEDURES ONLINE

摘要:

细胞衰老是一种肿瘤抑制性反应,其中细胞周期处于永久性停滞状态,可抑制肿瘤细胞增殖。近年来,诱导细胞衰老已被证明对抗肿瘤疗法至关重要,细胞衰老与肝细胞癌的临床预后和免疫治疗之间的联系仍然未知。我们对三个细胞衰老基因集中的基因进行富集分析,筛选了在肝细胞癌中显著富集的基因集,并从中提取基因。使用与衰老相关的基因构建签名,并在蛋白质和RNA水平验证其表达。在风险组之间分析了生存、临床分期和分级、免疫浸润、免疫治疗和药物敏感性。 q-PCR和免疫组化结果显示,在正常和肿瘤组织之间的签名基因表达中存在显著差异。风险组之间观察到临床病理特征、预后和免疫浸润的显著差异。在低风险组中,表现出较好的OS和较低的TMB分数,而高风险组具有更高的免疫检查点表达,以及更低的免疫逃逸风险。此外,我们发现高风险组对索拉非尼更敏感。综上所述,使用与衰老相关的基因构建的签名可以可靠地预测患者的预后和免疫治疗疗效,为肝细胞癌的免疫系统治疗提供了新思路。©2022.作者
Cellular senescence is a tumor suppressive response in which the cell cycle is in a state of permanent arrest and can inhibit tumor cell proliferation. In recent years, induction of cellular senescence has been shown to be important for antitumor therapy, and the link between cellular senescence and clinical prognosis and immunotherapy of hepatocellular carcinoma is still unknown.We performed enrichment analysis of genes in three cellular senescence gene sets, screened for gene sets significantly enriched in hepatocellular carcinoma and extracted genes from them. Signature were constructed using senescence-related genes, and their expression was verified at the protein and RNA levels. Survival, clinical staging and grading, immune infiltration, immunotherapy, and drug sensitivity were also analyzed between risk groups.The q-PCR and immunohistochemistry results revealed significant differences in the expression of the signature genes between normal and tumor tissues. Significant differences in clinicopathological features, prognosis and immune infiltration were observed between risk groups. In the low-risk group, better OS and lower TMB scores were demonstrated, while the high-risk group had higher immune checkpoint expression, as well as lower risk of immune escape. In addition, we found that the High-risk group was more sensitive to sorafenib.In summary, the signature constructed using aging-related genes can reliably predict patient prognosis and immunotherapy efficacy, providing a new idea for immune system therapy of hepatocellular carcinoma.© 2022. The Author(s).