Perturbation Analysis of a Prognostic DDX3X-Mediated Gene Expression Signature Identifies the Antimetastatic Potential of Chaetocin in Hepatocellular Carcinoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. TCGA Dataset Analysis
2.2. Ingenuity Pathway Analysis
2.3. Cell Culture
2.4. Lentivirus-Based shRNA Production and Infection
2.5. Cell Migration and Invasion Assay
2.6. Wound Healing Assay
2.7. Western Blot Analysis
2.8. Statistical Analysis
3. Results
3.1. DDX3X Expression Is Significantly Correlated with Poor Outcomes in Liver Cancer, and the Significantly Differential Gene Signature Was Identified after Comparison between Patient Groups with High and Low DDX3X Levels
3.2. Knowledge-Based Analysis of Gene Signatures Reveals the Potential for Triggering Cancer Metastasis and Progression
3.3. Knockdown of DDX3X Expression Inhibits Cell Migration and Invasion in a Liver Cancer Cell Line
3.4. Chaetocin Reverses the High DDX3X Expression-Mediated Gene Signature and Suppresses Liver Cancer Cell Migration
4. Conclusions
5. Discussion
Supplementary Materials
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Symbol | Cancer Type | Prognosis | Endpoint | p Value | Case | Dataset | Method | Probe ID |
---|---|---|---|---|---|---|---|---|
DDX3X | Glioma | - | Overall survival | N.S. | 153 | TCGA | RNA Seq | |
DDX3X | Thyroid Cancer | - | Overall survival | N.S. | 501 | TCGA | RNA Seq | |
DDX3X | Lung Cancer | - | Overall survival | N.S. | 994 | TCGA | RNA Seq | |
DDX3X | Colorectal Cancer | Good | Overall survival | 0.008 | 597 | TCGA | RNA Seq | |
DDX3X | Head and Neck Cancer | - | Overall survival | N.S. | 499 | TCGA | RNA Seq | |
DDX3X | Stomach Cancer | - | Overall survival | N.S. | 354 | TCGA | RNA Seq | |
DDX3X | Liver Cancer | Poor | Overall survival | 0.0012 | 365 | TCGA | RNA Seq | |
DDX3X | Pancreatic Cancer | Poor | Overall survival | 0.033 | 176 | TCGA | RNA Seq | |
DDX3X | Renal Cancer | - | Overall survival | N.S. | 877 | TCGA | RNA Seq | |
DDX3X | Urothelial Cancer | Good | Overall survival | 0.029 | 406 | TCGA | RNA Seq | |
DDX3X | Prostate Cancer | - | Overall survival | N.S. | 494 | TCGA | RNA Seq | |
DDX3X | Testis Cancer | - | Overall survival | N.S. | 134 | TCGA | RNA Seq | |
DDX3X | Breast cancer | Poor | Overall survival | 0.024 | 1075 | TCGA | RNA Seq | |
DDX3X | Cervical Cancer | - | Overall survival | N.S. | 291 | TCGA | RNA Seq | |
DDX3X | Endometrial Cancer | - | Overall survival | N.S. | 541 | TCGA | RNA Seq | |
DDX3X | Ovarian Cancer | - | Overall survival | N.S. | 373 | TCGA | RNA Seq | |
DDX3X | Melanoma | - | Overall survival | N.S. | 102 | TCGA | RNA Seq | |
DDX3X | Breast cancer | Poor | Relapse-free survival | <0.001 | 4929 | E-MTAB-365, E-TABM-43, GSE: 11121, 12093, | Array | 201210_at |
12276, 1456, 16391, 16446, 16716, 17705, 17907, | ||||||||
18728, 19615, 20194, 20271, 2034, 20685, 20711, | ||||||||
21653, 22093, 25066, 2603, 26971, 29044, 2990, | ||||||||
31448, 31519, 32646, 3494, 36771, 37946, 41998, | ||||||||
42568, 43358, 43365, 45255, 4611, 46184, 48390, | ||||||||
50948, 5327, 58812, 61304, 65194, 6532, 69031, | ||||||||
7390, 76275, 78958, 9195 | ||||||||
DDX3X | Ovarian cancer | Poor | Progression-free survival | <0.001 | 1435 | GSE: 14764, 15622, 18520, 19829, 23554, 26193, | Array | 201210_at |
26712, 27651, 30161, 3149, 51373, 63885, 65986, | RNA Seq | |||||||
9891, TCGA (N = 565) | ||||||||
DDX3X | Lung cancer | Good | Overall survival | <0.001 | 1925 | CAARRAY, GSE: 14814, 19188, 29013, 30219, | Array | 201210_at |
31210, 3141, 31908, 37745, 43580, 4573, 50081, | RNA Seq | |||||||
8894, TCGA (N = 133) | ||||||||
DDX3X | Gastric cancer | Good | Post progression survival | <0.001 | 498 | GSE: 14210, 15459, 22377, 29272, 51105, 62254 | Array | 201210_at |
Variable | Comparison | HR (95% CI) | p Value |
---|---|---|---|
Sex | M:F | 0.800 (0.562–1.141) | 0.218 |
Stage | 3–4:1–2 | 2.485 (1.714–3.603) | <0.001 |
T | T3–4:T1–2 | 2.578 (1.812–3.667) | <0.001 |
N | N1:N0 | 2.012 (0.493–8.212) | 0.330 |
M | M1:M0 | 4.055 (1.274–12.906) | 0.018 |
DDX3X | High:Low | 1.485 (1.050–2.099) | 0.025 |
Ranking | Categories | Diseases/Functions Annotation | Predicted Activation State | Activation z-Score |
---|---|---|---|---|
1 | Cellular Movement | Cell movement | Increased | 9.208 |
2 | Cellular Movement | Migration of cells | Increased | 8.506 |
3 | Cellular Assembly and Organization, Cellular Function and Maintenance | Organization of cytoplasm | Increased | 8.472 |
4 | Cellular Assembly and Organization, Cellular Function and Maintenance | Organization of cytoskeleton | Increased | 8.43 |
5 | Cellular Movement | Cell movement of tumor cell lines | Increased | 8.254 |
6 | Tissue Morphology | Quantity of cells | Increased | 8.25 |
7 | Cell Morphology, Cellular Assembly and Organization, Cellular Function and Maintenance | Formation of cellular protrusions | Increased | 8.077 |
8 | Cellular Assembly and Organization, Cellular Function and Maintenance | Microtubule dynamics | Increased | 7.699 |
9 | Cellular Development, Cellular Growth and Proliferation, Nervous System Development and Function, Tissue Development | Development of neurons | Increased | 6.967 |
10 | Cellular Movement | Homing of cells | Increased | 6.705 |
11 | Cellular Function and Maintenance | Cellular homeostasis | Increased | 6.55 |
12 | Cellular Movement | Invasion of cells | Increased | 6.461 |
13 | Cardiovascular System Development and Function | Development of vasculature | Increased | 6.43 |
14 | Cardiovascular System Development and Function, Organismal Development | Angiogenesis | Increased | 6.418 |
15 | Cellular Movement | Chemotaxis | Increased | 6.411 |
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Lin, T.-C. Perturbation Analysis of a Prognostic DDX3X-Mediated Gene Expression Signature Identifies the Antimetastatic Potential of Chaetocin in Hepatocellular Carcinoma. Cells 2023, 12, 1628. https://doi.org/10.3390/cells12121628
Lin T-C. Perturbation Analysis of a Prognostic DDX3X-Mediated Gene Expression Signature Identifies the Antimetastatic Potential of Chaetocin in Hepatocellular Carcinoma. Cells. 2023; 12(12):1628. https://doi.org/10.3390/cells12121628
Chicago/Turabian StyleLin, Tsung-Chieh. 2023. "Perturbation Analysis of a Prognostic DDX3X-Mediated Gene Expression Signature Identifies the Antimetastatic Potential of Chaetocin in Hepatocellular Carcinoma" Cells 12, no. 12: 1628. https://doi.org/10.3390/cells12121628