Jin RuiRi, Luo ZhiPeng, Tao Qing, Wang Peng, Cai XueSheng, Jiang LongZhou, Zeng ChunYan, Chen YouXiang
Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Abdominal Tumor Surgery, Jiangxi Cancer Hospital, Nanchang, China.
Front Oncol. 2023 Feb 16;13:1023292. doi: 10.3389/fonc.2023.1023292. eCollection 2023.
Colorectal cancer (CRC) is a highly prevalent malignancy with a poor prognosis. USP20 can support progression of variety of tumors. USP20 was shown to promote breast tumor metastasis, and proliferation of oral squamous carcinoma cells. However, the role of USP20 in CRC remains unclear.
We used bioinformatics to analyze the expression and prognosis of USP20 in pan-cancer and explore the relationship between USP20 expression and immune infiltration, immune checkpoints, and chemotherapy resistance in CRC. The differential expression and prognostic role of USP20 in CRC was validated by qRT-PCR and immunohistochemistry. Cox univariate and multivariate analyses were performed to assess risk factors for poor prognosis of CRC, and new prognostic prediction models were constructed and evaluated by decision curve analysis (ROC) and receiver operating characteristic (DCA). USP20 was overexpressed in CRC cell lines to explore the effect of USP20 on the functionalities of CRC cells. Enrichment analyses were used to explore the possible mechanism of USP20 in CRC.
The expression of USP20 was lower in CRC tissues than adjacent normal tissues. Compared with low USP20 expression patients, CRC patients with high USP20 expression level had shorter OS. Correlation analysis showed that USP20 expression was associated with lymph node metastasis. Cox regression analysis revealed USP20 as an independent risk factor for poor prognosis in CRC patients. ROC and DCA analyses showed that the performance of the newly constructed prediction model was better than the traditional TNM model. Immune infiltration analysis shown that USP20 expression is closely associated with T cell infiltration in CRC. A co-expression analysis showed that USP20 expression was positively correlated with several immune checkpoint genes including ADORA2A, CD160, CD27 and TNFRSF25 genes and positively associated with multiple multi-drug resistance genes such as MRP1, MRP3, and MRP5 genes. USP20 expression positively correlated with the sensitivity of cells to multiple anticancer drugs. Overexpression of USP20 enhanced the migration and invasive ability of CRC cells. Enrichment pathway analyses showed the USP20 may play a role the Notch pathway, Hedgehog pathway and beta-catenin pathway.
USP20 is downregulated in CRC and associated with prognosis in CRC. USP20 enhances CRC cells metastasis and is associated with immune infiltration, immune checkpoints, and chemotherapy resistance.
结直肠癌（CRC）是一种高度常见的恶性肿瘤，预后较差。泛素特异性蛋白酶20（USP20）可促进多种肿瘤的进展。已表明USP20可促进乳腺肿瘤转移及口腔鳞状癌细胞的增殖。然而，USP20在结直肠癌中的作用仍不清楚。
我们使用生物信息学分析USP20在泛癌中的表达及预后，并探讨USP20表达与结直肠癌免疫浸润、免疫检查点及化疗耐药性之间的关系。通过qRT-PCR和免疫组织化学验证USP20在结直肠癌中的差异表达及预后作用。进行Cox单因素和多因素分析以评估结直肠癌预后不良的危险因素，并通过决策曲线分析（ROC）和受试者工作特征（DCA）构建并评估新的预后预测模型。在结直肠癌细胞系中过表达USP20以探讨USP20对结直肠癌细胞功能的影响。采用富集分析探讨USP20在结直肠癌中的可能机制。
USP20在结直肠癌组织中的表达低于相邻正常组织。与USP20低表达患者相比，USP20高表达水平的结直肠癌患者总生存期较短。相关性分析表明USP20表达与淋巴结转移有关。Cox回归分析显示USP20是结直肠癌患者预后不良的独立危险因素。ROC和DCA分析表明新构建的预测模型的性能优于传统的TNM模型。免疫浸润分析显示USP20表达与结直肠癌中的T细胞浸润密切相关。共表达分析表明USP20表达与包括ADORA2A、CD160、CD27和TNFRSF25基因在内的多个免疫检查点基因呈正相关，并与多个多药耐药基因如MRP1、MRP3和MRP5基因呈正相关。USP20表达与细胞对多种抗癌药物的敏感性呈正相关。USP20的过表达增强了结直肠癌细胞的迁移和侵袭能力。富集通路分析表明USP20可能在Notch通路、Hedgehog通路和β-连环蛋白通路中发挥作用。
USP20在结直肠癌中表达下调且与结直肠癌的预后相关。USP20增强结直肠癌细胞转移，并与免疫浸润、免疫检查点及化疗耐药性相关。
