Clinicopathologic features of TDO2 overexpression in renal cell carcinoma

Pham, Quoc Thang; Taniyama, Daiki; Sekino, Yohei; Akabane, Shintaro; Babasaki, Takashi; Kobayashi, Go; Sakamoto, Naoya; Sentani, Kazuhiro; Oue, Naohide; Yasui, Wataru

doi:10.1186/s12885-021-08477-1

Cited by 6 publications

(5 citation statements)

References 32 publications

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“…In ccRCC, interference with TIM-3 protein expression can attenuate the invasion ability by aggravating anoikis ( Yu et al, 2017 ). Knockdown of anoikis-related protein Tryptophan 2,3-dioxygenase (TDO2) inhibits the proliferation and invasion of RCC cells and may be a promising marker for RCC targeted therapy ( Pham et al, 2021 ). Quinazolines trigger anoikis in RCC by targeting the focal adhesion survival signaling, resulting in potent antitumor effects ( Sakamoto et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

A novel anoikis-related prognostic signature associated with prognosis and immune infiltration landscape in clear cell renal cell carcinoma

Chen

Liu²,

Zhu³

et al. 2022

Front. Genet.

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Background: Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma (RCC). Anoikis plays an essential function in tumourigenesis, whereas the role of anoikis in ccRCC remains unclear.Methods: Anoikis-related genes (ARGs) were collected from the MSigDB database. According to univariate Cox regression analysis, the least absolute shrinkage and selection operator (LASSO) algorithm was utilized to select the ARGs associated with the overall rate (OS). Multivariate Cox regression analysis was conducted to identify 5 prognostic ARGs, and a risk model was established. The Kaplan-Meier survival analysis was used to evaluate the OS rate of ccRCC patients. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Gene set enrichment analysis (GSVA) were utilized to investigate the molecular mechanism of patients in the low- and high-risk group. ESTIMATE, CIBERSOT, and single sample gene set enrichment analysis (ssGSEA) algorithms were conducted to estimate the immune infiltration landscape. Consensus clustering analysis was performed to divide the patients into different subgroups.Results: A fresh risk model was constructed based on the 5 prognostic ARGs (CHEK2, PDK4, ZNF304, SNAI2, SRC). The Kaplan-Meier survival analysis indicated that the OS rate of patients with a low-risk score was significantly higher than those with a high-risk score. Consensus clustering analysis successfully clustered the patients into two subgroups, with a remarkable difference in immune infiltration landscape and prognosis. The ESTIMATE, CIBERSORT, and ssGSEA results illustrated a significant gap in immune infiltration landscape of patients in the low- and high-risk group. Enrichment analysis and GSVA revealed that immune-related signaling pathways might mediate the role of ARGs in ccRCC. The nomogram results illustrated that the ARGs prognostic signature was an independent prognostic predictor that distinguished it from other clinical characteristics. TIDE score showed a promising immunotherapy response of ccRCC patients in different risk subgroups and cluster subgroups.Conclusion: Our study revealed that ARGs play a carcinogenic role in ccRCC. Additionally, we firstly integrated multiple ARGs to establish a risk-predictive model. This study highlights that ARGs could be implemented as a stratification factor for individualized and precise treatment in ccRCC patients.

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Section: Introductionmentioning

confidence: 99%

A novel anoikis-related prognostic signature associated with prognosis and immune infiltration landscape in clear cell renal cell carcinoma

Chen

Liu²,

Zhu³

et al. 2022

Front. Genet.

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“…Recently, experimental evidence suggested a direct effect of TDO on tumor cell survival and proliferation. Moreover, we and others have shown that it promotes growth, migration, and invasiveness of cancer cells, including melanomas ( Pham QT. et al, 2021 ; Cecchi et al, 2021 ).…”

Section: Discussionmentioning

confidence: 94%

“…In Pham’s study ( Pham Q. T. et al, 2021 ), TDO was shown to be up regulated in bladder cancer cells, stimulating their growth and invasiveness. Interestingly, TDO was found to be necessary for spheroid formation in these cells, suggesting that it could be a potential marker for targeted therapy in bladder cancer ( Pham QT. et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells via Tryptophan 2,3 Dioxygenase

Cecchi

Mannini²,

Lapucci³

et al. 2022

Front. Pharmacol.

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In addition to its well-established immunosuppressive actions, tryptophan 2,3-dioxygenase (TDO) appears to elicit direct effects on tumor cell function. Although TDO has been associated with cancer stemness, its involvement in melanoma stem cell biology remains largely unknown. Since we showed that by upregulating TDO, dexamethasone (dex) promotes proliferation and migration of SK-Mel-28 human melanoma cells, we sought to investigate dex effects on melanoma spherogenesis and stemness, and whether these events are mediated by TDO. We demonstrate here that dex significantly upregulates TDO in A375, a more aggressive melanoma cell line, confirming that dex effects are not limited to SK-Mel-28 cells. Moreover, dex stimulates spherogenesis of both cell lines, which is mediated by TDO, evident by its suppression with 680C91, a TDO inhibitor. The formed melanospheres appear to be enriched with embryonic stem cell marker mRNAs, the expression of which is potentiated by dex. Expression of cancer stem cell markers (CD133, CD44, ganglioside GD2) was significantly increased in A375 spheres, as detected by flow cytometry. Taken together, our results suggest that TDO could represent a promising target in the management of melanoma and that dex, routinely used as a co-medication also in advanced melanoma, may stimulate melanoma cell function/tumor-supporting properties, a rather debilitating and undesired side effect.

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“…In addition, TDO2 was shown to overexpress in liver metastases from UVM and may be related to metastatic potential [33]. TDO2 expression was upregulated in renal cell carcinoma and was associated with worse outcomes [34]. These results imply that aberrant TDO2 expression plays a vital role in the development of cancer.…”

Section: Discussionmentioning

confidence: 95%

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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Clinicopathologic features of TDO2 overexpression in renal cell carcinoma

Cited by 6 publications

References 32 publications

A novel anoikis-related prognostic signature associated with prognosis and immune infiltration landscape in clear cell renal cell carcinoma

A novel anoikis-related prognostic signature associated with prognosis and immune infiltration landscape in clear cell renal cell carcinoma

Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells via Tryptophan 2,3 Dioxygenase

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

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