Tryptophan 2, 3‑dioxygenase promotes proliferation, migration and invasion of ovarian cancer cells

Zhao, Yuemei; Tao, Fengxing; Jiang, Jiayu; Chen, Lina; Du, Jizao; Cheng, Xiaoxiao; He, Qiaojun; Zhong, Shouhui; Chen, Wei; Wu, Xiaoli; Ou, Rongying; Xu, Yunsheng; Tang, Kai-Fu

doi:10.3892/mmr.2021.12084

Cited by 11 publications

(16 citation statements)

References 45 publications

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“…In the present study, we identified that TDO2 is highly expressed in 20 types of cancer, including BLCA, BRCA, CESC, COAD, ESCA, GBM, HNSC, KIRC, LUAD, LUSC, OV, PAAD, PRAD, READ, SKCM, STAD, TGCT, THCA, UCEC, and UCS, which are in line with previous findings [8][9][10][24][25][26][27][28]. However, Wu et al found that TDO2 was overexpressed in HCC, and their overexpression was correlated with tumor progression and poor prognosis [29,30], which contradicts our current results.…”

Section: Discussionsupporting

confidence: 93%

Pancancer Analysis of Revealed TDO2 as a Biomarker of Prognosis and Immunotherapy

et al. 2022

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Background. Tryptophan 2,3-dioxygenase (TDO) encoded by TDO2, a rate-limiting enzyme in the kynurenine pathway, catabolizes tryptophan to kynurenine, evades immune surveillance, and promotes tumor growth. Although accumulating evidence suggests a crucial role of TDO2 during tumor formation and development, systematic evaluation of TDO2 across human cancers has rarely been reported. Methods. To shed more light on the role of TDO2 in human cancer, we explored the expression profiles of TDO2 and identified its prognostic value in pancancer analysis through TCGA, CCLE, and GTEx databases. We further utilized TCGA data to evaluate the association between TDO2 and tumor immunological features, such as mismatch repair (MMR), tumor immune infiltration, immune checkpoint-related genes, tumor mutational burden (TMB), microsatellite instability (MSI), and DNA methyltransferase (DNMT). Results. TDO2 exhibited different expression levels in various cancer cell lines. Frequently, TDO2 was detected to be highly expressed in the majority of cancers. In addition, high TDO2 expression was correlated with an unfavorable prognosis for patients in KIRP, LGG, TGCT, and UVM. Moreover, high TDO2 expression level positively correlated with higher immune infiltration, especially dendritic cells. Additionally, there is a close relationship between TDO2 and immune checkpoint-related gene markers, such as LAIR1, CD276, NRP1, CD80, and CD86. Finally, correlation analysis has demonstrated a high-correlation between TDO2 and TMB, MSI, MMR, and DNMT of multiple cancer types. Conclusion. Therefore, our results suggest that TDO2 can function as a potential prognostic biomarker due to its role in tumor immunity regulation.

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Section: Discussionsupporting

confidence: 93%

Pancancer Analysis of Revealed TDO2 as a Biomarker of Prognosis and Immunotherapy

et al. 2022

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“…The IDO1 expression pattern in our OCCC cohort was different from that in ovarian serous carcinoma, previously reported to range from 59% to 71%. 32,41 Efforts should be made to validate our findings.…”

Section: T a B L E 3 Relations Between Expression Of Trp Catabolising...mentioning

confidence: 81%

“…In line with this, high IDO expression in ovarian cancer cells was found to be correlated with lower levels of tumour‐infiltrating lymphocytes, advanced surgical stage and decreased survival 13 . Similarly, TDO2 catabolises the degradation of Trp to Kyn and is upregulated in ovarian cancer tissues compared with normal ovarian tissues, promoting the proliferation, migration and invasion of ovarian cancer cells 32 . Recently, overexpression of IL4I1 was shown to activate AHR and promote tumour progression 22 .…”

Section: Introductionmentioning

confidence: 77%

Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma

Zhang,

Gao,

Wang

et al. 2023

Cancer Medicine

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AimAs the second most prevalent subtype of epithelial ovarian cancers, ovarian clear cell carcinoma (OCCC) is known for its chemoresistance to conventional platinum‐based therapy. In this work, we examined the tryptophan (Trp) metabolism enzymes' differential expression in patients with OCCC to assess the potential for personalised treatment.MethodsA total of 127 OCCC tissues were used to construct tissue microarrays, and immunohistochemistry (IHC) staining of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 was performed. The correlations between Trp enzyme expression and clinical characteristics were analysed.ResultsPositive IDO1, IDO2, TDO2 and IL4I1 staining was identified in 26.8%, 94.5%, 75.6% and 82.7% of OCCC respectively. IDO1‐positive samples were more common in the chemoresistant group than in the platinum‐sensitive group (46.7% vs. 19.8%). Moreover, positive expression of IDO1, TDO2 and IL4I1 was related to advanced stage, metastasis, bilateral tumours, endometriosis and tumour rupture (p < 0.05) respectively. Univariate analysis revealed a significant association between bilateral tumours, lymph node metastasis, advanced stage, distant metastasis and aberrant cytology with a poor prognosis for OCCC, while the absence of residual tumour was correlated with a favourable outcome (p < 0.05). However, only bilateral tumours and lymph node metastases were related to a poor prognosis after multivariate analysis.ConclusionThis is the first study to investigate the expression of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 in OCCC tissues. IDO2, TDO2 and IL4I1 were detected in the majority of OCCC. Clinical traits were correlated with IDO1, IDO2, TDO2 and IL4I1 expression. IDO1 may be used as a therapeutic target given the large percentage of chemoresistant cases with IDO1 expression. These results will aid the development of personalised therapies for OCCC.

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“…It is reported that TDO2 is highly expressed in many tumors and promotes tumor progression, and as a promising cancer treatment target, it has attracted more and more attention. Reports revealed that inhibition of TDO2 can repress the proliferation, migration and invasion of ovarian cancer and colorectal cancer ( 44 , 45 ). The prognostic signature was probably associated with TDO2 expression and TDO2 checkpoint pathway in ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Construction of a prognostic signature for serous ovarian cancer based on lactate metabolism-related genes

Xiang

et al. 2022

Front. Oncol.

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Background:The key biochemical feature of malignant tumor is the conversion of energy metabolism from oxidative phosphorylation to glycolysis, which provides sufficient capacity and raw materials for tumor cell rapid growth. Our study aims to construct a prognostic signature for ovarian cancer based on lactate metabolism-related genes (LMRGs).Methods: Data of ovarian cancer and non-diseased ovarian data were downloaded from TCGA and the GTEx database, respectively. LMRGs were obtained from GeneCards and MSigDB databases, and the differentially expressed LMRGs were identified using limma and DESeq2 R packages. Cox regression analysis and LASSO were performed to determine the LMRGs associated with OS and develop the prognostic signature. Then, clinical significance of the prognostic signature in ovarian cancer was assessed.Results: A total of 485 differentially expressed LMRGs in ovarian tissue were selected for subsequent analysis, of which 324 were up-regulated and 161 were down regulated. We found that 22 LMRGs were most significantly associated with OS by using the univariate regression analysis. The prognostic scoring model was consisted of 12 LMRGs (SLCO1B3, ERBB4, SLC28A1, PDSS1, BDH1, AIFM1, TSFM, PPARGC1A, HGF, FGFR1, ABCC8, TH). Kaplan-Meier survival analysis indicated that poorer overall survival (OS) in the high-risk group patients (P<0.0001). This prognostic signature could be an independent prognostic indicator after adjusting to other clinical factors. The calibration curves of nomogram for the signature at 1, 2, and 3 years and the ROC curve demonstrated good agreement between the predicted and observed survival rates of ovarian cancer patients. Furthermore, the high-risk group patients have much lower expression level of immune checkpoint-TDO2 compared with the low-risk group (P=0.024). Conclusions:We established a prognostic signature based on LMRGs for ovarian cancer, and highlighted emerging evidence indicating that this Frontiers in Oncology frontiersin.org 01

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Tryptophan 2, 3‑dioxygenase promotes proliferation, migration and invasion of ovarian cancer cells

Cited by 11 publications

References 45 publications

Pancancer Analysis of Revealed TDO2 as a Biomarker of Prognosis and Immunotherapy

Pancancer Analysis of Revealed TDO2 as a Biomarker of Prognosis and Immunotherapy

Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma

Construction of a prognostic signature for serous ovarian cancer based on lactate metabolism-related genes

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