DDX10 and BYSL as the potential targets of chondrosarcoma and glioma

Quan, Xuemin; Zhao, Changsong; Gao, Zhengrong; Zhang, Yao; Zhao, Rugang; Wang, Jingjing; Zhang, Qiang

doi:10.1097/md.0000000000027669

Cited by 5 publications

(5 citation statements)

References 42 publications

(86 reference statements)

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“…[12] There have been many studies on DM from chondrosarcoma. For example, DDX10 and BYSL are presumed to be potential targets for chondrosarcoma, [20] in addition to IDH1/2 and COL2A1 as possible therapeutic targets for chondrosarcoma. [21] However, these studies are based on the molecular level and not on clinical features.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for distant metastasis of chondrosarcoma: A population-based study

Deng,

Wang,

Tan

et al. 2023

Medicine

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Chondrosarcoma is the second largest bone malignancy after osteosarcoma and mainly affects middle-aged adults, where patients with distant metastasis (DM) often have a poor prognosis. Although nomograms have been widely used to predict distant tumor metastases, there is a lack of large-scale data studies for the diagnostic evaluation of DM in chondrosarcoma. Data on patients diagnosed with chondrosarcoma from 2004 to 2015 were obtained from the Surveillance, Epidemiology, and End Results database. Independent risk factors for having DM from chondrosarcoma were screened using univariate and multivariate logistics regression analysis. A nomogram was created to predict the probability of DM from the screened independent risk factors. The nomogram was then validated using receiver operating characteristic curves and calibration curves. A total of 1870 chondrosarcoma patients were included in the study after data screening, of which 157 patients (8.40%) had DM at the time of diagnosis. Univariate and multivariate logistic regression analysis screened four independent risk factors, including grade, tumor number, T stage, and N stage. receiver operating characteristic curves and calibration curves showed good accuracy of the nomogram in both training and validation sets. The current study screened for independent risk factors for DM from chondrosarcoma, which will help clinicians evaluate patients.

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Section: Discussionmentioning

confidence: 99%

Risk factors for distant metastasis of chondrosarcoma: A population-based study

Deng,

Wang,

Tan

et al. 2023

Medicine

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“…This study was done regarding MIQE recommendation 23. The expression of IGFBP4 and TAGLN was detected by RT-qPCR 18 , 20 . GAPDH was used as the control gene.…”

Section: Methodsmentioning

confidence: 99%

“…Bioinformatics studies biological problems using the methods of applied mathematics, informatics, statistics, and computer science. Some studies have researched the expression profile of RNA in osteosarcoma by using bioinformatics methods and found that bioinformatics analysis might be one valuable tool for the research of osteosarcoma 18 , 19 .…”

Section: Introductionmentioning

confidence: 99%

Low expression of IGFBP4 and TAGLN accelerate the poor overall survival of osteosarcoma

Liu

Shen

2022

Sci Rep

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Osteosarcoma is a common malignant bone tumor characterized by the production of osteoid stroma by the tumor. However, effect of IGFBP4 and TAGLN on the survival of osteosarcoma is unclear. The GEO database was used to identify the differentially expressed genes (DEGs) between control samples and osteosarcoma. Genes for biological process (BP), cellular composition (CC), and molecular function (MF) were examined using DAVID, Metascape, and GSEA. GSE14359 and GSE36001 were downloaded in the GEO database. GEO2R was used to find DEGs between control samples and osteosarcoma. The cytoHubb also found the hub genes of IGFBP4 and TAGLN. The Kaplan–Meier method was used to analyze overall survival. A total of 134 patients with osteosarcoma were enrolled in this study. The RNA levels of IGFBP4 and TAGLN were evaluated by RT-qPCR. The correlation between IGFBP4 and TAGLN expression and their associations with clinical indicators were analyzed using Spearman's rho test and Pearson's Chi-squared test. Univariate and multivariate Cox regression analyses were used to determine the potential prognostic factors. And the animal model was used to verify the role of hub genes on the osteosarcoma by the RT-qPCR and immunofluorescence. Support Vector Machine (SVM) was performed to construct the correlation among the expression of IGFBP4, TAGLN, and osteosarcoma. Through bioinformatics, IGFBP4 and TAGLN were identified as the hub genes of osteosarcoma. And osteosarcoma patients with high expression levels of IGFBP4 (HR = 0.56, P = 0.013) and TAGLN (HR = 0.52, P = 0.012) had better overall survival times than those with low expression levels. The results showed that pathologic grade (P = 0.017), tumor metastasis (P < 0.001), and enneking stage (P < 0.001) were significantly correlated with IGFBP4. Also, pathologic grade (P = 0.002), tumor metastasis (P < 0.001), and enneking stage (P < 0.001) were significantly related to the TAGLN. Spearman’s correlation coefficient displayed that IGFBP4 were significantly correlated with the tumor metastasis (ρ = − 0.843, P < 0.001), enneking stage (ρ = − 0.500, P < 0.001), and TAGLN (ρ = 0.821, P < 0.001). IGFBP4 (HR = 0.252, 95% CI 0.122–0.517, P < 0.001) and TAGLN (HR = 0.155, 95% CI 0.089–0.269, P < 0.001) were significantly associated with overall survival. Based on the qPCR and immunofluorescence, IGFBP4 and TAGLN were down-regulated in the osteosarcoma tissue than the control group. And the SVM presented that there exists strong relationship among the expression of IGFBP4, TAGLN, and osteosarcoma. IGFBP4 and TAGLN may be attractive molecular targets for osteosarcoma, opening a new avenue for research into the disease.

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“…Another exciting prospect is to identify SL and SDL partners that have already been implicated in cell apoptosis in a cancer-specific manner or whose DEAD/H-box helicase partners, when overexpressed, have a putative apoptotic nature. An elevated expression of DDX10 in cancer leads to a poor survival rate in chondrosarcoma patients ( 78 ). Additionally, inhibition of α-synuclein displays tumor growth suppression in melanoma cells ( 189 ).…”

Section: Exploiting Dead/h-box Helicases For Synthetic Lethality Appr...mentioning

confidence: 99%

Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy

et al. 2023

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DEAD/H-box helicases are implicated in virtually every aspect of RNA metabolism, including transcription, pre-mRNA splicing, ribosomes biogenesis, nuclear export, translation initiation, RNA degradation, and mRNA editing. Most of these helicases are upregulated in various cancers and mutations in some of them are associated with several malignancies. Lately, synthetic lethality (SL) and synthetic dosage lethality (SDL) approaches, where genetic interactions of cancer-related genes are exploited as therapeutic targets, are emerging as a leading area of cancer research. Several DEAD/H-box helicases, including DDX3, DDX9 (Dbp9), DDX10 (Dbp4), DDX11 (ChlR1), and DDX41 (Sacy-1), have been subjected to SL analyses in humans and different model organisms. It remains to be explored whether SDL can be utilized to identity druggable targets in DEAD/H-box helicase overexpressing cancers. In this review, we analyze gene expression data of a subset of DEAD/H-box helicases in multiple cancer types and discuss how their SL/SDL interactions can be used for therapeutic purposes. We also summarize the latest developments in clinical applications, apart from discussing some of the challenges in drug discovery in the context of targeting DEAD/H-box helicases.

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DDX10 and BYSL as the potential targets of chondrosarcoma and glioma

Cited by 5 publications

References 42 publications

Risk factors for distant metastasis of chondrosarcoma: A population-based study

Risk factors for distant metastasis of chondrosarcoma: A population-based study

Low expression of IGFBP4 and TAGLN accelerate the poor overall survival of osteosarcoma

Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy

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