Abstract：
BACKGROUND: 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.
CONCLUSIONS: Our data show that TDO2 might be a crucial marker for predicting prognosis and targeted therapy 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.
CONCLUSIONS: Our data show that TDO2 might be a crucial marker for predicting prognosis and targeted therapy in GC.
摘要：
背景：色氨酸代谢已被证明与肿瘤的发展有关。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），可以有效促进不同类型癌症的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）的独立预后因素。这项工作旨在揭示TDO2在GC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和两个不同GC队列的公开数据中评估了TDO2的表达。研究了TDO2与免疫细胞浸润以及PD-L1肿瘤染色之间的相关性。用MTT检查TDO2的生物功能，菌落形成,和通过RNA干扰的球体形成测定。
结果：TDO2表达与疾病进展和临床结局相关，其表达是GC预后的独立预测因子。TDO2表达与免疫细胞浸润和肿瘤PD-L1表达相关。抑制TDO2表达抑制细胞增殖，菌落形成,和GC细胞的细胞侵袭。此外,TDO2表达的抑制抑制了GC类器官的球状体形成和活力。
结论：我们的数据表明，TDO2可能是预测GC预后和靶向治疗的关键指标。
方法：在癌症基因组图谱队列STAD和两个不同GC队列的公开数据中评估了TDO2的表达。研究了TDO2与免疫细胞浸润以及PD-L1肿瘤染色之间的相关性。用MTT检查TDO2的生物功能，菌落形成,和通过RNA干扰的球体形成测定。
结果：TDO2表达与疾病进展和临床结局相关，其表达是GC预后的独立预测因子。TDO2表达与免疫细胞浸润和肿瘤PD-L1表达相关。抑制TDO2表达抑制细胞增殖，菌落形成,和GC细胞的细胞侵袭。此外,TDO2表达的抑制抑制了GC类器官的球状体形成和活力。
结论：我们的数据表明，TDO2可能是预测GC预后和靶向治疗的关键指标。
