Identification of Prognostic Factors in Cholangiocarcinoma Based on Integrated ceRNA Network Analysis

Jin, Haili; Liu, Wei; Xü, Wei; Zhou, Liping; Luo, Huarong; Xu, Cheng; Chen, Xi; Chen, Wenbin

doi:10.1155/2022/7102736

Cited by 3 publications

(3 citation statements)

References 46 publications

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“…These substrates can serve as potential biomarkers of LDHD deficiency, providing differential diagnostic criteria for D-lactic acidosis patients with LDHD mutations or with short bowel syndrome. In addition to D-lactic acidosis, down-regulation of LDHD expression is related to poor prognosis of many tumors such as cholangiocarcinoma and renal cell carcinoma 58 , 59 . Besides, elevated LDHD expression is found in prostate cancer cells, which exhibit higher mitochondrial D-lactate metabolism than normal cells 60 .…”

Section: Discussionmentioning

confidence: 99%

Lactate dehydrogenase D is a general dehydrogenase for D-2-hydroxyacids and is associated with D-lactic acidosis

Jin,

Chen,

Yang

et al. 2023

Nat Commun

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Mammalian lactate dehydrogenase D (LDHD) catalyzes the oxidation of D-lactate to pyruvate. LDHD mutations identified in patients with D-lactic acidosis lead to deficient LDHD activity. Here, we perform a systematic biochemical study of mouse LDHD (mLDHD) and determine the crystal structures of mLDHD in FAD-bound form and in complexes with FAD, Mn2+ and a series of substrates or products. We demonstrate that mLDHD is an Mn2+-dependent general dehydrogenase which exhibits catalytic activity for D-lactate and other D-2-hydroxyacids containing hydrophobic moieties, but no activity for their L-isomers or D-2-hydroxyacids containing hydrophilic moieties. The substrate-binding site contains a positively charged pocket to bind the common glycolate moiety and a hydrophobic pocket with some elasticity to bind the varied hydrophobic moieties of substrates. The structural and biochemical data together reveal the molecular basis for the substrate specificity and catalytic mechanism of LDHD, and the functional roles of mutations in the pathogenesis of D-lactic acidosis.

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Section: Discussionmentioning

confidence: 99%

Lactate dehydrogenase D is a general dehydrogenase for D-2-hydroxyacids and is associated with D-lactic acidosis

Jin,

Chen,

Yang

et al. 2023

Nat Commun

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“…A previous study highlighted the critical involvement of ELF4 in the cancer immune response ( 40 ). It has also been reported to be associated with immune cell infiltration and immune-related feature genes (CD14, CD163, CD33) in cholangiocarcinoma ( 41 ). Similarly, the present study revealed that ELF4 expression in ccRCC was closely related to the infiltration levels of multiple immune cell types compared with ELF3 and ELF5.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of E47‑like factors and verification of ELF4 in clear cell renal cell carcinoma

Lü

Zhang

et al. 2023

Oncol Lett

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Clear cell renal cell carcinoma (ccRCC) is the most prominent subtype of renal cancer and E47-like factors (ELFs) are important in tumorigenesis; however, the specific role of key ELFs in ccRCC remains unclear. The present study comprehensively analyzed RNA sequencing and clinical data from multiple databases, and identified differentially expressed ELFs (ELF3-5) in ccRCC. The DNA promoter methylation, genetic variation and clinical significance of ELF3-5 in ccRCC were analyzed using the cBioPortal and UALCAN databases. The association between ELF3-5 and multiple immune cell infiltration was analyzed using Tumor Immune Estimation Resource. Subsequently, ELF4 was selected and its association with biological functions was assessed. Cell counting kit-8 (CCK-8), colony formation, Transwell, macrophage chemotaxis and polarization assays were conducted to validate the functions of ELF4. Notably, the mRNA expression levels of ELF4 were significantly upregulated in ccRCC, whereas ELF3 and ELF5 mRNA expression levels were significantly downregulated. Clinical significance analysis revealed that ELF4 showed a high clinical significance with tumor grade, clear cell type A and B subtypes, and incidence rates of amplification in genetic variation. Further analyses indicated that ELF4 may be involved in multiple immune cell differentiation. Additionally, cell experiments revealed that ELF4 inhibition downregulated 769-P and 786-O proliferation, migration and invasion. Knockdown of ELF4 in cancer cells also inhibited M2 macrophage polarization and chemotaxis towards 769-P and 786-O cells. Conclusively, the present findings indicated the clinical significance of ELF4 in ccRCC, and verified its key role in driving cell proliferation, migration and invasion, and promoting M2 macrophage polarization and chemotaxis in ccRCC.

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“…The relationship between the DEmiRNAs and DElncRNAs was predicted using DIANA-LncBasev2 [ 18 , 19 ], and the correlation of DEmiRNAs and mRNA using starBase (Version 2.0) [ 20 ]. Subsequently, we retained the negative regulation among DEmiRNAs, DElncRNAs and mRNA.…”

Section: Methodsmentioning

confidence: 99%

A risk model based on lncRNA-miRNA-mRNA gene signature for predicting prognosis of patients with bladder cancer

Zhao,

Cao,

Wang

et al. 2024

Cancer Biomarkers

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OBJECTIVES: We aimed to analyze lncRNAs, miRNAs, and mRNA expression profiles of bladder cancer (BC) patients, thereby establishing a gene signature-based risk model for predicting prognosis of patients with BC. METHODS: We downloaded the expression data of lncRNAs, miRNAs and mRNA from The Cancer Genome Atlas (TCGA) as training cohort including 19 healthy control samples and 401 BC samples. The differentially expressed RNAs (DERs) were screened using limma package, and the competing endogenous RNAs (ceRNA) regulatory network was constructed and visualized by the cytoscape. Candidate DERs were screened to construct the risk score model and nomogram for predicting the overall survival (OS) time and prognosis of BC patients. The prognostic value was verified using a validation cohort in GSE13507. RESULTS: Based on 13 selected. lncRNAs, miRNAs and mRNA screened using L1–penalized algorithm, BC patients were classified into two groups: high-risk group (including 201 patients ) and low risk group (including 200 patients). The high-risk group’s OS time ( hazard ratio [HR], 2.160; 95% CI, 1.586 to 2.942; P= 5.678e-07) was poorer than that of low-risk groups’ (HR, 1.675; 95% CI, 1.037 to 2.713; P= 3.393 e-02) in the training cohort. The area under curve (AUC) for training and validation datasets were 0.852. Younger patients (age ⩽ 60 years) had an improved OS than the patients with advanced age (age > 60 years) (HR 1.033, 95% CI 1.017 to 1.049; p= 2.544E-05). We built a predictive model based on the TCGA cohort by using nomograms, including clinicopathological factors such as age, recurrence rate, and prognostic score. CONCLUSIONS: The risk model based on 13 DERs patterns could well predict the prognosis for patients with BC.

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Identification of Prognostic Factors in Cholangiocarcinoma Based on Integrated ceRNA Network Analysis

Cited by 3 publications

References 46 publications

Lactate dehydrogenase D is a general dehydrogenase for D-2-hydroxyacids and is associated with D-lactic acidosis

Lactate dehydrogenase D is a general dehydrogenase for D-2-hydroxyacids and is associated with D-lactic acidosis

Comprehensive analysis of E47‑like factors and verification of ELF4 in clear cell renal cell carcinoma

A risk model based on lncRNA-miRNA-mRNA gene signature for predicting prognosis of patients with bladder cancer

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