Novel Therapies for Tongue Squamous Cell Carcinoma Patients with High-Grade Tumors
Abstract
:1. Introduction
2. Material and Methods
2.1. Data Processing and Differential Expression Analysis
2.2. Selection of Grade-Associated Genes
2.3. Functional Enrichment Analysis
2.4. Identification of Survival Analysis of Hub Genes
2.5. Enrichment Scores of Immune Cell Types
2.6. Structure-Based Virtual Screening
2.7. ADMET (Adsorption, Distribution, Metabolism, Excretion, and Toxicity) Prediction
2.8. Statistical Analysis and Ethics Statement
3. Results
3.1. Identification of DEGs and Grade-Associated Genes
3.2. Enrichment Analysis on Grade-Associated Genes
3.3. Protein–Protein Interaction (PPI) and Hub Proteins
3.4. Validation of Hub Genes in Independent Data Sets
3.5. Correlation of Hub Genes with Immune Cell Enrichment Scores
3.6. Virtual Screening of Compounds
3.7. Pharmacologic Properties of Compounds
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
TSCC | Tongue squamous cell carcinoma |
OSCC | oral squamous cell carcinoma |
TCGA | The Cancer Genome Atlas |
CDKs | cyclin-dependent kinases |
DEGs | differentially expressed genes |
PPI | protein–protein interaction |
ORR | objective response rate |
KEGG | Kyoto Encyclopedia of genes and Genomes |
GO | Gene Ontology |
BP | biological process |
CC | cellular component |
MF | molecular function |
OS | overall survival |
ssGSEA | single sample gene set enrichment analysis |
PDB | Protein Data Bank |
ADMET | adsorption, distribution, metabolism, excretion, and toxicity |
DTP | developmental toxicity potential |
BUB1 | budding uninhibited by benzimidazoles 1 |
CCNB2 | cyclin B2 |
CDC6 | cell division cycle 6 |
CDC20 | cell division cycle 20 |
CDK1 | cyclin dependent kinase 1 |
MCM2 | minichromosome maintenance complex component 2 |
TMB | tumor mutational burden |
EMT | epithelial-to-mesenchymal transition |
HIV | human immunodeficiency virus |
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ID | Term | p-Value | Count |
---|---|---|---|
KEGG:hsa04110 | Cell Cycle | <0.01 | 15 |
KEGG:hsa04810 | Regulation of Actin Cytoskeleton | <0.01 | 14 |
KEGG:hsa04510 | Focal Adhesion | <0.01 | 13 |
KEGG:hsa04512 | ECM-Receptor Interaction | <0.01 | 11 |
KEGG:hsa04914 | Progesterone-mediated Oocyte Maturation | <0.01 | 11 |
GO_BP:0048285 | Organelle Fission | <0.01 | 48 |
GO_BP:0000280 | Nuclear Division | <0.01 | 47 |
GO_BP:0007059 | Chromosome Segregation | <0.01 | 45 |
GO_BP:0140014 | Mitotic Nuclear Division | <0.01 | 42 |
GO_BP:0043062 | Extracellular Structure Organization | <0.01 | 40 |
GO_CC:0031012 | Extracellular Matrix | <0.01 | 41 |
GO_CC:0005819 | Spindle | <0.01 | 38 |
GO_CC:0062023 | Collagen-containing Extracellular Matrix | <0.01 | 38 |
GO_CC:0098687 | Chromosomal Region | <0.01 | 33 |
GO_CC:0000775 | Chromosome, Centromeric Region | <0.01 | 28 |
GO_MF:0048037 | Cofactor Binding | <0.01 | 28 |
GO_MF:0003779 | Actin Binding | <0.01 | 24 |
GO_MF:0050662 | Coenzyme Binding | <0.01 | 22 |
GO_MF:0005201 | Extracellular Matrix Structural Constituent | <0.01 | 19 |
GO_MF:1901681 | Sulfur Compound Binding | <0.01 | 18 |
Datasets\Genes | BUB1 | CCNB2 | CDC6 | CDC20 | CDK1 | MCM2 |
---|---|---|---|---|---|---|
TSCC (TCGA) | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 |
GSE30784 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 | p < 0.01 |
GSE9844 | 0.23 | 0.019 | p < 0.01 | p < 0.01 | 0.033 | p < 0.01 |
GSE13601 | p < 0.01 | p < 0.01 | 0.14 | p < 0.01 | p < 0.01 | p < 0.01 |
Protein | ZincID | Libdock Score |
---|---|---|
CDC20 | ZINC3799072 | 116.1 |
CDC20 | ZINC100052685 | 105.9 |
CDC20 | ZINC3785268 | 105.6 |
CDK1 | ZINC8214703 | 126.7 |
CDK1 | ZINC21297660 | 113.4 |
CDK1 | ZINC601250 | 111.8 |
MCM2 | ZINC28232755 | 171.2 |
MCM2 | ZINC85537014 | 166.8 |
MCM2 | ZINC28639340 | 161.7 |
Compounds | Solubility Level | BBB Level | CYP2D6 | Hepatotoxicity | Absorption Level | PPB Level |
---|---|---|---|---|---|---|
ZINC3799072 | 3 | 2 | 1 | 0 | 0 | 1 |
ZINC100052685 | 2 | 4 | 0 | 0 | 1 | 1 |
ZINC3785268 | 3 | 2 | 1 | 0 | 0 | 1 |
ZINC8214703 | 3 | 4 | 0 | 0 | 0 | 1 |
ZINC21297660 | 3 | 3 | 0 | 0 | 0 | 1 |
ZINC601250 | 1 | 0 | 1 | 1 | 1 | 1 |
ZINC28232755 | 1 | 4 | 0 | 0 | 3 | 0 |
ZINC85537014 | 3 | 4 | 1 | 1 | 2 | 0 |
ZINC28639340 | 3 | 4 | 0 | 1 | 2 | 1 |
Compounds | Mouse NTP (Female) | Mouse NTP (Male) | Rat NTP (Female) | Rat NTP (Male) | Ames | DTP |
---|---|---|---|---|---|---|
ZINC3799072 | 0 | 0 | 0 | 0 | 0 | 1 |
ZINC100052685 | 0 | 0 | 0 | 0 | 0 | 0 |
ZINC3785268 | 0 | 0 | 0 | 0 | 0 | 1 |
ZINC8214703 | 0 | 0 | 0 | 0 | 0 | 0 |
ZINC21297660 | 0 | 1 | 0 | 1 | 0 | 1 |
ZINC601250 | 0 | 1 | 0 | 0 | 0 | 1 |
ZINC28232755 | 0 | 0 | 0 | 0 | 0 | 1 |
ZINC85537014 | 0 | 0 | 0 | 0 | 0 | 0 |
ZINC28639340 | 0 | 0 | 0 | 0 | 0 | 1 |
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Li, Y.; Lin, H.; Chen, L.; Chen, Z.; Li, W. Novel Therapies for Tongue Squamous Cell Carcinoma Patients with High-Grade Tumors. Life 2021, 11, 813. https://doi.org/10.3390/life11080813
Li Y, Lin H, Chen L, Chen Z, Li W. Novel Therapies for Tongue Squamous Cell Carcinoma Patients with High-Grade Tumors. Life. 2021; 11(8):813. https://doi.org/10.3390/life11080813
Chicago/Turabian StyleLi, Yinghua, Hao Lin, Lu Chen, Zihao Chen, and Weizhong Li. 2021. "Novel Therapies for Tongue Squamous Cell Carcinoma Patients with High-Grade Tumors" Life 11, no. 8: 813. https://doi.org/10.3390/life11080813