A genetic database can be utilized to identify potential biomarkers for biphenotypic hepatocellular carcinoma-cholangiocarcinoma

Mok, Shaffer; Mohan, Sachin; Grewal, Navjot; Elfant, Adam B.; Judge, Thomas A.

doi:10.21037/jgo.2016.04.01

Cited by 8 publications

(6 citation statements)

References 46 publications

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“…EDNRB, a tumor suppressor, is very frequently methylated in hepatocellular carcinoma tissues (14). EDNRB was previously identified as a biomarker for hepatocellular carcinoma (38). This suggested that hsa-miR-10b-3p may serve a crucial role in the process of hepatocellular carcinoma by regulating EDNRB.…”

Section: Discussionmentioning

confidence: 96%

Uncovering the potential differentially expressed miRNAs as diagnostic biomarkers for hepatocellular carcinoma based on machine learning in The Cancer Genome Atlas database

et al. 2020

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The present study aimed to identify novel diagnostic differentially expressed microRNAs (miRNAs/miRs) in order to understand the molecular mechanisms underlying hepatocellular carcinoma. The expression data of miRNA and mRNA were downloaded for differential expression analysis. Optimal diagnostic differentially expressed miRNA biomarkers were identified via a random forest algorithm. Classification models were established to distinguish patients with hepatocellular carcinoma and normal individuals. A regulatory network between optimal diagnostic differentially expressed miRNA and differentially expressed mRNAs was then constructed. The GSE63046 dataset and in vitro experiments were used to validate the expression of the optimal diagnostic differentially expressed miRNAs identified. In addition, diagnostic and prognostic analyses of optimal diagnostic differentially expressed miRNAs were performed. In total, 14 differentially expressed miRNAs (all upregulated) and 2,982 differentially expressed mRNAs (1,989 upregulated and 993 downregulated) were identified. hsa-miR-10b-5p, hsa-miR-10b-3p, hsa-miR-224-5p, hsa-miR-183-5p and hsa-miR-182-5p were considered as the optimal diagnostic biomarkers for hepatocellular carcinoma. The mRNAs targeted by these five miRNAs included secreted frizzled related protein 1 (SFRP1), endothelin receptor type B (EDNRB), nuclear receptor subfamily 4 group A member 3 (NR4A3), four and a half LIM domains 2 (FHL2), NK3 homeobox 1 (NKX3-1), interleukin 6 signal transducer (IL6ST) and forkhead box O1 (FOXO1). 'Bile acid biosynthesis and cholesterol' was the most enriched signaling pathways of these target mRNAs. The expression validation of the five miRNAs was consistent with the present bioinformatics analysis. Notably, hsa-miR-10b-5p and hsa-miR-10b-3p had a significant prognosis value for patients with hepatocellular carcinoma. In conclusion, the five differentially expressed miRNAs may be considered as diagnostic biomarkers for patients with hepatocellular carcinoma. In addition, the differential expression levels of the targets of these five mRNAs, including SFRP1, EDNRB, NR4A3, FHL2, NKX3-1, IL6ST and FOXO1, may be involved in hepatocellular carcinoma tumorigenesis.

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Section: Discussionmentioning

confidence: 96%

Uncovering the potential differentially expressed miRNAs as diagnostic biomarkers for hepatocellular carcinoma based on machine learning in The Cancer Genome Atlas database

et al. 2020

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“…The targets for colorectal cancer (CRC) were obtained from four databases, namely Drugbank ( https://go.drugbank.com/ ) ( 36 ), GeneCards ( https://genecards.weizmann.ac.il/v3/ ) ( 37 ), TTD ( https://db.idrblab.net/ttd/ ) ( 38 ), and Dis-GeNET ( https://www.disgenet.org/ ) ( 39 ). The search results from these databases were integrated, and any duplicate targets were eliminated.…”

Section: Methodsmentioning

confidence: 99%

Mechanism of Bazhen decoction in the treatment of colorectal cancer based on network pharmacology, molecular docking, and experimental validation

Lu,

Sun,

Zhou

et al. 2023

Front. Immunol.

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ObjectiveBazhen Decoction (BZD) is a common adjuvant therapy drug for colorectal cancer (CRC), although its anti-tumor mechanism is unknown. This study aims to explore the core components, key targets, and potential mechanisms of BZD treatment for CRC.MethodsThe Traditional Chinese Medicine Systems Pharmacology (TCMSP) was employed to acquire the BZD’s active ingredient and targets. Meanwhile, the Drugbank, Therapeutic Target Database (TTD), DisGeNET, and GeneCards databases were used to retrieve pertinent targets for CRC. The Venn plot was used to obtain intersection targets. Cytoscape software was used to construct an “herb-ingredient-target” network and identify core targets. GO and KEGG pathway enrichment analyses were conducted using R language software. Molecular docking of key ingredients and core targets of drugs was accomplished using PyMol and Autodock Vina software. Cell and animal research confirmed Bazhen Decoction efficacy and mechanism in treating colorectal cancer.ResultsBZD comprises 173 effective active ingredients. Using four databases, 761 targets related to CRC were identified. The intersection of BZD and CRC yielded 98 targets, which were utilized to construct the “herb-ingredient-target” network. The four key effector components with the most targets were quercetin, kaempferol, licochalcone A, and naringenin. Protein-protein interaction (PPI) analysis revealed that the core targets of BZD in treating CRC were AKT1, MYC, CASP3, ESR1, EGFR, HIF-1A, VEGFR, JUN, INS, and STAT3. The findings from molecular docking suggest that the core ingredient exhibits favorable binding potential with the core target. Furthermore, the GO and KEGG enrichment analysis demonstrates that BZD can modulate multiple signaling pathways related to CRC, like the T cell receptor, PI3K-Akt, apoptosis, P53, and VEGF signaling pathway. In vitro, studies have shown that BZD dose-dependently inhibits colon cancer cell growth and invasion and promotes apoptosis. Animal experiments have shown that BZD treatment can reverse abnormal expression of PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53 genes. BZD also increases the ratio of CD4+ T cells to CD8+ T cells in the spleen and tumor tissues, boosting IFN-γ expression, essential for anti-tumor immunity. Furthermore, BZD has the potential to downregulate the PD-1 expression on T cell surfaces, indicating its ability to effectively restore T cell function by inhibiting immune checkpoints. The results of HE staining suggest that BZD exhibits favorable safety profiles.ConclusionBZD treats CRC through multiple components, targets, and metabolic pathways. BZD can reverse the abnormal expression of genes such as PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53, and suppresses the progression of colorectal cancer by regulating signaling pathways such as PI3K-AKT, P53, and VEGF. Furthermore, BZD can increase the number of T cells and promote T cell activation in tumor-bearing mice, enhancing the immune function against colorectal cancer. Among them, quercetin, kaempferol, licochalcone A, naringenin, and formaronetin are more highly predictive components related to the T cell activation in colorectal cancer mice. This study is of great significance for the development of novel anti-cancer drugs. It highlights the importance of network pharmacology-based approaches in studying complex traditional Chinese medicine formulations.

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“…Targets associated with CRC were collected from Drugbank [ 30 ] ( https://www.drugbank.ca ), TTD [ 31 ] ( http://db.idrblab.net/ttd/ ), DisGeNET [ 32 ] ( http://www.disgenet.org/ ), and GeneCards [ 33 ] ( https://www.genecards.org ). Then the retrieval results of these databases were merged, and only one repeated target was reserved.…”

Section: Methodsmentioning

confidence: 99%

Molecular Targets and Mechanisms of Hedyotis diffusa-Scutellaria barbata Herb Pair for the Treatment of Colorectal Cancer Based on Network Pharmacology and Molecular Docking

Yang

Lü

Tang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective: Hedyotis diffusa-Scutellaria barbata herb pair (HS) has therapeutic effects on a variety of cancers, and this study aims to systematically explore the multiple mechanisms of HS in the treatment of colorectal cancer (CRC). Methods. The active ingredients of HS were obtained from TCMSP, and the potential targets related to these ingredients were screened from the STITCH, SuperPred, and Swiss TargetPrediction databases. Targets associated with CRC were retrieved by Drugbank, TTD, DisGeNET, and GeneCards. We used a Venn diagram to screen the intersection targets and used Cytoscape to construct the herb-ingredient-target-disease network, and the core targets were selected. The Go analysis and KEGG pathway annotation were performed by R language software. We used PyMol and Autodock Vina to achieve molecular docking of core ingredients and targets. Results: A total of 33 active ingredients were obtained from the HS, and 762 CRC-related targets were reserved from the four databases. We got 170 intersection targets to construct the network and found that the four ingredients with the most targets were quercetin, luteolin, baicalein, and dinatin, which were the core ingredients. The PPI analysis showed that the core targets were STAT3, TP53, MAPK3, AKT1, JUN, EGFR, MYC, VEGFA, EGF, and CTNNB1. Molecular docking results showed that these core ingredients had good binding potential with core targets, especially the docking of each component with MAPK obtained the lowest binding energy. HS acts simultaneously on various signaling pathways related to CRC, including the PI3K-Akt signaling pathway, proteoglycans in cancer, and the MAPK signaling pathway. Conclusions: This study systematically analyzed the active ingredients, core targets, and central mechanisms of HS in the treatment of CRC. It reveals the role of HS targeting PI3K-Akt signaling and MAPK signaling pathways in the treatment of CRC. We hope that our research could bring a new perspective to the therapy of CRC and find new anticancer drugs.

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A genetic database can be utilized to identify potential biomarkers for biphenotypic hepatocellular carcinoma-cholangiocarcinoma

Cited by 8 publications

References 46 publications

Uncovering the potential differentially expressed miRNAs as diagnostic biomarkers for hepatocellular carcinoma based on machine learning in The Cancer Genome Atlas database

Uncovering the potential differentially expressed miRNAs as diagnostic biomarkers for hepatocellular carcinoma based on machine learning in The Cancer Genome Atlas database

Mechanism of Bazhen decoction in the treatment of colorectal cancer based on network pharmacology, molecular docking, and experimental validation

Molecular Targets and Mechanisms of Hedyotis diffusa-Scutellaria barbata Herb Pair for the Treatment of Colorectal Cancer Based on Network Pharmacology and Molecular Docking

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