High expression of <scp>DARS2</scp> indicates poor prognosis in lung adenocarcinoma

Jiang, Yihui; You, Jianbin; Wu, Chuncai; Kang, Yanli; Chen, Falin; Chen, Liangyuan; Wu, Wenbing

doi:10.1002/jcla.24691

Cited by 9 publications

(8 citation statements)

References 24 publications

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“…DARS2 has been identified as a hepatocellular carcinoma (HCC) oncogene that promotes HCC cell cycle progression and inhibits HCC cell apoptosis (83). In lung adenocarcinoma cells, DARS2 is involved in proliferation, invasion, and apoptosis and shows promise as a therapeutic target (84). MAFF could promote tumor invasion and metastasis through IL11 and STAT3 signaling (85).…”

Section: Discussionmentioning

confidence: 99%

A novel hypoxia- and lactate metabolism-related signature to predict prognosis and immunotherapy responses for breast cancer by integrating machine learning and bioinformatic analyses

Hao²,

Wu³

et al. 2022

Front. Immunol.

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BackgroundBreast cancer is the most common cancer worldwide. Hypoxia and lactate metabolism are hallmarks of cancer. This study aimed to construct a novel hypoxia- and lactate metabolism-related gene signature to predict the survival, immune microenvironment, and treatment response of breast cancer patients.MethodsRNA-seq and clinical data of breast cancer from The Cancer Genome Atlas database and Gene Expression Omnibus were downloaded. Hypoxia- and lactate metabolism-related genes were collected from publicly available data sources. The differentially expressed genes were identified using the “edgeR” R package. Univariate Cox regression, random survival forest (RSF), and stepwise multivariate Cox regression analyses were performed to construct the hypoxia-lactate metabolism-related prognostic model (HLMRPM). Further analyses, including functional enrichment, ESTIMATE, CIBERSORTx, Immune Cell Abundance Identifier (ImmuCellAI), TIDE, immunophenoscore (IPS), pRRophetic, and CellMiner, were performed to analyze immune status and treatment responses.ResultsWe identified 181 differentially expressed hypoxia-lactate metabolism-related genes (HLMRGs), 24 of which were valuable prognostic genes. Using RSF and stepwise multivariate Cox regression analysis, five HLMRGs were included to establish the HLMRPM. According to the medium-risk score, patients were divided into high- and low-risk groups. Patients in the high-risk group had a worse prognosis than those in the low-risk group (P < 0.05). A nomogram was further built to predict overall survival (OS). Functional enrichment analyses showed that the low-risk group was enriched with immune-related pathways, such as antigen processing and presentation and cytokine-cytokine receptor interaction, whereas the high-risk group was enriched in mTOR and Wnt signaling pathways. CIBERSORTx and ImmuCellAI showed that the low-risk group had abundant anti-tumor immune cells, whereas in the high-risk group, immunosuppressive cells were dominant. Independent immunotherapy datasets (IMvigor210 and GSE78220), TIDE, IPS and pRRophetic analyses revealed that the low-risk group responded better to common immunotherapy and chemotherapy drugs.ConclusionsWe constructed a novel prognostic signature combining lactate metabolism and hypoxia to predict OS, immune status, and treatment response of patients with breast cancer, providing a viewpoint for individualized treatment.

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Section: Discussionmentioning

confidence: 99%

A novel hypoxia- and lactate metabolism-related signature to predict prognosis and immunotherapy responses for breast cancer by integrating machine learning and bioinformatic analyses

Hao²,

Wu³

et al. 2022

Front. Immunol.

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“…DARS2 is responsible for producing the enzyme that ensures the correct translation of the genetic code by attaching amino acids to their corresponding tRNA molecules in the mitochondria ( 9 , 11 , 24 ). Liu and colleagues discovered that DARS2 can serve as a prognostic marker for non-adenocarcinomas and promote the proliferation, invasion, and migration of lung adenocarcinoma cells while inhibiting cell apoptosis ( 17 , 25 , 26 ). It suggests that DARS2 may be proposed as a new biomarker to distinguish between multiple myeloma and lung adenocarcinoma ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

“…It suggests that DARS2 may be proposed as a new biomarker to distinguish between multiple myeloma and lung adenocarcinoma ( 27 ). It has been found that DARS2 is an oncogene in hepatocellular carcinoma and can promote the progression of the hepatocellular carcinoma cell cycle while inhibiting apoptosis in HCC cells ( 16 , 17 ). Although Wu’s team discovered that DARS2 can predict overall survival in BLCA and serve as a predictive model for assessing clinical outcomes ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…It reported an upregulation of DARS2 expression in lung adenocarcinoma and highlighted its role in regulating the proliferation, invasion, and apoptosis of lung adenocarcinoma cells. Moreover, DARS2 overexpression was associated with poor prognosis in lung adenocarcinoma ( 17 ). However, the biological role of DARS2 in BLCA has not yet been completely researched.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic biomarker DARS2 correlated with immune infiltrates in bladder tumor

Yang,

Ma,

Deng

et al. 2024

Front. Immunol.

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BackgroundDARS2 is a pivotal member of the Aminoacyl-tRNA synthetases family that is critical for regulating protein translation. However, the biological role of DARS2 in bladder cancer remains elusive.MethodsWe analyzed the correlation between DARS2 expression and prognosis, tumor stage, and immune infiltration in bladder cancer using The Cancer Genome Atlas (TCGA) database. We validated findings in clinical samples from The First Affiliated Hospital of Nanchang University and explored the biological functions of DARS2 using cell and animal models.ResultsWe found DARS2 to be upregulated in bladder cancer, associated with tumor progression and poor prognosis. Immune infiltration analysis suggested that DARS2 may facilitate immune evasion by modulating PD-L1. Cell and animal experiments validated that DARS2 knockdown and overexpress can inhibit or increase cancer cell proliferation, metastasis, tumorigenesis, immune escape, and PD-L1 levels.ConclusionsOur study reveals DARS2 as a potential prognostic biomarker and immunotherapy target in BLCA.

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“…Jiang et al analyzed the TCGA dataset and found that DARS2 was highly expressed in LUAD samples, and its expression level was related to tumor stage, T stage, and M stage. However, the relationship between DARS2 and clinicopathological characteristics was not verified by clinical cohort [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

DARS2 overexpression is associated with PET/CT metabolic parameters and affects glycolytic activity in lung adenocarcinoma

Liu,

Yuan,

Gao

et al. 2023

J Transl Med

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Background This study investigated the correlation between the expression of DARS2 and metabolic parameters of 18F-FDG PET/CT, and explored the potential mechanisms of DARS2 affecting the proliferation and glycolysis of lung adenocarcinoma (LUAD) cells. Methods This study used genomics and proteomics to analyze the difference in DARS2 expression between LUAD samples and control samples. An analysis of 62 patients with LUAD who underwent 18F-FDG PET/CT examinations before surgery was conducted retrospectively. The correlation between DARS2 expression and PET/CT metabolic parameters, including SUVmax, SUVmean, MTV, and TLG, was examined by Spearman correlation analysis. In addition, the molecular mechanism of interfering with DARS2 expression in inhibiting LUAD cell proliferation and glycolysis was analyzed through in vitro cell experiments. Results DARS2 expression was significantly higher in LUAD samples than in control samples (p < 0.001). DARS2 has high specificity (98.4%) and sensitivity (95.2%) in the diagnosis of LUAD. DARS2 expression was positively correlated with SUVmax, SUVmean, and TLG (p < 0.001). At the same time, the sensitivity and specificity of SUVmax in predicting DARS2 overexpression in LUAD were 88.9% and 65.9%, respectively. In vitro cell experiments have shown that interfering with DARS2 expression can inhibit the proliferation and migration of LUAD cells, promote cell apoptosis, and inhibit the glycolytic activity of tumor cells by inhibiting the expression of glycolytic related genes SLC2A1, GPI, ALDOA, and PGAM1. Conclusions Overexpression of DARS2 is associated with metabolic parameters on 18F-FDG PET/CT, which can improve LUAD diagnosis accuracy. DARS2 may be a useful biomarker to diagnose, prognosis, and target treatment of LUAD patients.

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High expression of DARS2 indicates poor prognosis in lung adenocarcinoma

Cited by 9 publications

References 24 publications

A novel hypoxia- and lactate metabolism-related signature to predict prognosis and immunotherapy responses for breast cancer by integrating machine learning and bioinformatic analyses

A novel hypoxia- and lactate metabolism-related signature to predict prognosis and immunotherapy responses for breast cancer by integrating machine learning and bioinformatic analyses

Prognostic biomarker DARS2 correlated with immune infiltrates in bladder tumor

DARS2 overexpression is associated with PET/CT metabolic parameters and affects glycolytic activity in lung adenocarcinoma

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