色氨酸2,3-双加氧酶可能是癌症潜在的预后生物标志物和免疫治疗靶点：一项荟萃分析和生物信息学分析
Tryptophan 2,3-dioxygenase may be a potential prognostic biomarker and immunotherapy target in cancer: A meta-analysis and bioinformatics analysis.
作者信息
Hu Yanyan, Liu Zhongjian, Tang Hui
机构信息
Department of Gastroenterology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
Medical School, Kunming University of Science and Technology, Kunming, China.
出版信息
Front Oncol. 2022 Oct 3;12:977640. doi: 10.3389/fonc.2022.977640. eCollection 2022.
BACKGROUND
Tryptophan 2,3-dioxygenase (TDO2) is one of the emerging immune checkpoints. Meanwhile, TDO2 is also a key enzyme in the tryptophan (Trp)-kynurenine (Kyn) signaling pathway. Many studies have evaluated that TDO2 is highly expressed in various malignant tumor patients and plays a prognostic role. However, the sample size of a single prognostic study was small, and the results were still controversial.
METHODS
We used Stata software and referenced the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement to conduct a meta-analysis on TDO2 and its clinical features and prognosis. We searched the PubMed, Cochrane Library, and Web of Science databases to find publications concerning TDO2 expression in malignant tumor patients up to June 2021. We used the Newcastle-Ottawa Scale (NOS) to evaluate the bias risk of the included literature. Risk ratios (RRs) and hazard ratios (HRs) were used for clinical outcomes, specifically overall survival (OS) and progression-free survival (PFS). In addition, we used data from The Cancer Genome Atlas (TCGA) to verify our conclusions.
RESULTS
Nine studies including 667 patients with malignant tumors were identified. Our results suggested that overexpression of TDO2 was statistically correlated with poor OS and poor PFS (HR = 2.58, 95% CI = 1.52-4.40, = 0.0005; HR = 2.38, 95% CI = 0.99-5.73, = 0.05). In terms of clinicopathological characteristics, the overexpression level of TDO2 was statistically correlated with TNM (tumor-node-metastasis) stage (RR = 0.65, 95% CI = 0.48-0.89, = 0.002) and regional lymph node metastasis (RR = 0.76, 95% CI = 0.59-0.99, = 0.04). Subgroup analysis revealed the potential sources of heterogeneity. In addition, bioinformatics studies suggested that the level of TDO2 was high in malignant tumors and higher in cancer tissue than in matched paracarcinoma tissue. Gene enrichment analysis showed that TDO2 was closely related to immune response.
CONCLUSION
Overall, TDO2 may be a biomarker for the survival and prognosis of patients with malignant tumors and a potential therapeutic target in the future.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=260442, identifier (CRD42021260442).
背景
色氨酸2,3-双加氧酶（TDO2）是新出现的免疫检查点之一。同时，TDO2也是色氨酸（Trp）-犬尿氨酸（Kyn）信号通路中的关键酶。许多研究评估发现，TDO2在各种恶性肿瘤患者中高表达并发挥预后作用。然而，单个预后研究的样本量较小，结果仍存在争议。
方法
我们使用Stata软件，并参考系统评价与Meta分析的首选报告项目（PRISMA）声明，对TDO2及其临床特征和预后进行Meta分析。我们检索了PubMed、Cochrane图书馆和Web of Science数据库，以查找截至2021年6月有关恶性肿瘤患者TDO2表达的出版物。我们使用纽卡斯尔-渥太华量表（NOS）评估纳入文献的偏倚风险。风险比（RRs）和风险比（HRs）用于临床结局，特别是总生存期（OS）和无进展生存期（PFS）。此外，我们使用来自癌症基因组图谱（TCGA）的数据来验证我们的结论。
结果
共纳入9项研究，包括667例恶性肿瘤患者。我们的结果表明，TDO2过表达与较差的OS和较差的PFS在统计学上相关（HR = 2.58，95%CI = 1.52 - 4.40，P = 0.0005；HR = 2.38，95%CI = 0.99 - 5.73，P = 0.05）。在临床病理特征方面，TDO2的过表达水平与TNM（肿瘤-淋巴结-转移）分期在统计学上相关（RR = 0.65，95%CI = 0.48 - 0.89，P = 0.002）和区域淋巴结转移（RR = 0.76，95%CI = 0.59 - 0.99，P = 0.04）。亚组分析揭示了异质性的潜在来源。此外，生物信息学研究表明，TDO2在恶性肿瘤中的水平较高，且在癌组织中高于匹配的癌旁组织。基因富集分析表明，TDO2与免疫反应密切相关。
结论
总体而言，TDO2可能是恶性肿瘤患者生存和预后的生物标志物，也是未来潜在的治疗靶点。
系统评价注册
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=260442，标识符（CRD42021260442）。
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