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Highly expressed carbohydrate sulfotransferase 11 correlates with unfavorable prognosis and immune evasion of hepatocellular carcinoma
Cancer Medicine ( IF 2.9 ) Pub Date : 2022-09-05 , DOI: 10.1002/cam4.5186
Dan-Dan Xiong 1 , Jian-di Li 1 , Rong-Quan He 2 , Ming-Xuan Li 1 , Yan-Qing Pan 1 , Xiao-Lian He 1 , Yi-Wu Dang 1 , Gang Chen 1
Affiliation  

Despite great advance has been made in multi-modality treatments for HCC patients, the effectiveness is far from satisfactory with worse survival outcome, which may be partly explainable by the anti-tumor deficiency of the immune system. It is necessary to clarify the molecular mechanism of HCC immunodeficiency. Here, we demonstrated that carbohydrate sulfotransferase 11 (CHST11) was upregulated in HCC and related to advanced TNM stage. HCC patients with TP53 mutation showed higher CHST11 expression. Survival analysis revealed that CHST11 was an independent prognostic biomarker in HCC. Cellular functional experiments indicated that knockdown of CHST11 in HCC inhibited cell proliferation and metastasis. Gene functional enrichment analyses indicated that CHST11 modulated pathways related to tumor growth, metastasis and immune regulation. Continuative immune-related analyses revealed that CHST11 expression facilitated Tregs infiltration in HCC and promoted the expression of checkpoints PD-L1/PD-1, resulting in the immunosuppression of HCC. Targeting CHST11 may inhibit Tregs infiltration and enhance the antineoplastic effect of immune checkpoint inhibitors, which provides a novel insight into the combination immunotherapy with Treg-modulating agents and PD-L1/PD-1 inhibitors.

中文翻译:


高表达的碳水化合物磺基转移酶11与肝细胞癌的不良预后和免疫逃避相关



尽管肝癌患者的多模式治疗取得了很大进展,但其疗效仍远不能令人满意,生存结果较差,这可能部分是由于免疫系统抗肿瘤缺陷所致。有必要阐明HCC免疫缺陷的分子机制。在这里,我们证明了碳水化合物磺基转移酶 11 (CHST11) 在 HCC 中表达上调,并且与晚期 TNM 分期相关。 TP53突变的HCC患者表现出较高的CHST11表达。生存分析显示 CHST11 是 HCC 的独立预后生物标志物。细胞功能实验表明,HCC 中 CHST11 的敲低可抑制细胞增殖和转移。基因功能富集分析表明CHST11调节与肿瘤生长、转移和免疫调节相关的通路。连续免疫相关分析显示,CHST11的表达促进HCC中Treg细胞的浸润,并促进检查点PD-L1/PD-1的表达,从而导致HCC的免疫抑制。靶向CHST11可能抑制Treg细胞浸润,增强免疫检查点抑制剂的抗肿瘤作用,这为Treg调节剂与PD-L1/PD-1抑制剂联合免疫治疗提供了新的思路。
更新日期:2022-09-05
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