TDO2在胃癌中的重要作用:TDO2与癌症进展、患者生存、PD-L1表达和癌症干细胞相关。

IF 3.5 4区医学 Q3 CELL BIOLOGY

Pathobiology Pub Date : 2023-01-01 DOI:10.1159/000523750

Quoc Thang Pham, Daiki Taniyama, Shintaro Akabane, Tsuyoshi Takashima, Ryota Maruyama, Yohei Sekino, Kazuhiro Sentani, Wataru Yasui, Naohide Oue

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引用次数: 4

摘要

色氨酸代谢已被证明参与肿瘤的发展。两种主要的色氨酸降解酶，色氨酸2,3-双加氧酶(TDO2)和吲哚胺2,3-双加氧酶1 (IDO1)，可能在多种类型的癌症中有效地促进癌细胞存活和远处转移，如肺癌和乳腺癌。IDO1过表达是胃癌(GC)的独立预后指标。本工作旨在揭示TDO2在胃癌中的表达及其临床病理意义。方法:在癌症基因组图谱队列STAD的公开数据和两个不同的GC队列中评估TDO2的表达。探讨TDO2与免疫细胞浸润及PD-L1肿瘤染色的相关性。采用MTT法、集落形成法和RNA干扰法检测TDO2的生物功能。结果:TDO2表达与疾病进展及临床结局均相关，其表达是胃癌预后的独立预测因子。TDO2表达与免疫细胞浸润及肿瘤PD-L1表达相关。抑制TDO2表达可抑制胃癌细胞的增殖、集落形成和细胞侵袭。此外，抑制TDO2表达可抑制球状体的形成和GC类器官的活力。结论:我们的数据显示TDO2可能是预测胃癌预后和靶向治疗的重要指标。

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Essential Roles of TDO2 in Gastric Cancer: TDO2 Is Associated with Cancer Progression, Patient Survival, PD-L1 Expression, and Cancer Stem Cells.

Introduction: Tryptophan metabolism has been shown to be involved in tumor development. Two main tryptophan-degrading enzymes, tryptophan 2,3-dioxygenase (TDO2) and indoleamine 2,3-dioxygenase 1 (IDO1), may potently promote cancer cell survival and distant metastasis in diverse types of cancer, such as lung and breast cancer. IDO1 overexpression is an independent prognosticator in gastric cancer (GC). This work aimed to uncover the expression of TDO2 and its clinicopathologic significance in GC.

Methods: TDO2 expression was evaluated in public data of The Cancer Genome Atlas cohort STAD and in two different GC cohorts. Correlation between TDO2 and immune cell infiltrates as well as PD-L1 tumor staining was investigated. The biofunction of TDO2 was examined with MTT, colony formation, and spheroid formation assays by RNA interference.

Results: TDO2 expression was correlated with both progressive disease and clinical outcome, and its expression was an independent predictor of prognosis in GC. TDO2 expression was correlated with infiltration of immune cells and tumor expression of PD-L1. Inhibition of TDO2 expression suppressed cell proliferation, colony formation, and cell invasion of GC cells. Additionally, suppression of TDO2 expression inhibited spheroid body-formation and viability of GC organoids.

Conclusion: Our data show that TDO2 might be a crucial marker for predicting prognosis and targeted therapy in GC.

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来源期刊

Pathobiology 医学-病理学

CiteScore

8.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： ''Pathobiology'' offers a valuable platform for the publication of high-quality original research into the mechanisms underlying human disease. Aiming to serve as a bridge between basic biomedical research and clinical medicine, the journal welcomes articles from scientific areas such as pathology, oncology, anatomy, virology, internal medicine, surgery, cell and molecular biology, and immunology. Published bimonthly, ''Pathobiology'' features original research papers and reviews on translational research. The journal offers the possibility to publish proceedings of meetings dedicated to one particular topic.