Screening Plasma Exosomal RNAs as Diagnostic Markers for Cervical Cancer: An Analysis of Patients Who Underwent Primary Chemoradiotherapy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Blood Samples and Clinical Data
2.2. Screening Process
2.2.1. Statistical Screening
2.2.2. Biological Screening
2.3. Statistical Analysis of Differential RNA Expression
2.4. Multidimensional Scaling and Heatmap Construction
2.5. Network Analysis
2.6. Ingenuity Pathway Analysis
2.7. Receiver Operative Characteristic Analysis
2.8. Table and Boxplots
3. Results
3.1. Clinical Characteristics
3.2. Statistical Screening
3.3. Biological Screening
3.3.1. miRNA
3.3.2. lncRNA
3.3.3. mRNA
3.3.4. snoRNA
3.3.5. piRNA, snRNA, tRNA, and yRNA
3.4. DEG in snoRNA
3.5. Integration
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Normal | Cancer | DEG in snoRNA | p | ||
---|---|---|---|---|---|
(n = 12) | (n = 30) | No (n = 18) | Yes (n = 12) | ||
Age (years) | 49.2 ± 11.6 | 49.9 ± 10.1 | 47.9 ± 11.4 | 52.8 ± 7.1 | 0.199 |
FIGO stage 2018 | 0.627 | ||||
| 5 (16.7%) | 4 (22.2%) | 1 (8.3%) | ||
| 15 (50.0%) | 9 (50.0%) | 6 (50.0%) | ||
| 7 (23.3%) | 4 (22.2%) | 3 (25.0%) | ||
| 3 (10.0%) | 1 (5.6%) | 2 (16.7%) | ||
Pathology | 0.374 | ||||
| 5 (16.7%) | 4 (22.2%) | 1 (8.3%) | ||
| 1 (3.3%) | 0 (0.0%) | 1 (8.3%) | ||
| 1 (3.3%) | 1 (5.6%) | 0 (0.0%) | ||
| 23 (76.7%) | 13 (72.2%) | 10 (83.3%) | ||
Radiotherapy field | 0.464 | ||||
Pelvis | 21 (70.0%) | 14 (77.8%) | 7 (58.3%) | ||
Pelvis with paraaortic region | 9 (30.0%) | 4 (22.2%) | 5 (41.7%) | ||
Hemoglobin (g/dl) | |||||
Pretreatment | 12.1 ± 1.5 | 12.0 ± 1.5 | 12.2 ± 1.6 | 0.78 | |
Second week during CCRT | 11.1 ± 1.4 | 11.3 ± 1.2 | 10.8 ± 1.7 | 0.336 | |
Absolute lymphocyte count (cells/μL) | |||||
Pretreatment | 1754 ± 470 | 1758 ± 451 | 1747 ± 518 | 0.95 | |
First week after CCRT | 931 ± 393 | 929 ± 281 | 936 ± 546 | 0.966 | |
Second week after CCRT | 511 [371; 632] | 575 [505; 661] | 384 [323; 466] | 0.008 | |
Pretreatment tumor marker (ng/mL) | |||||
Squamous cell carcinoma antigen | 3.7 [0.9; 16.6] | 2.2 [0.8; 4.8] | 13.1 [4.0; 60.6] | 0.016 | |
Cytokeratin fragment 21-1 | 2.5 [1.8; 10.2] | 2.2 [1.2; 2.8] | 8.4 [2.5; 16.6] | 0.031 | |
Pretreatment tumor volume (cm3) | 50.5 [18.1; 94.1] | 40.6 [15.2; 94.1] | 61.0 [30.9; 103.3] | 0.346 |
RNA | Known Biological Functions | Tissue | Suggested Biological Functions | Exosome |
---|---|---|---|---|
miR-142-3p | Tumor suppressor [20] | ↓(CC) [21] | Tumor suppressor | ↓ |
ARL6IP5 | Tumor suppressor (https://bioinfo.uth.edu/TSGene/ accessed on 1 September 2021) | ↓(STT) [22] | Tumor suppressor | ↓ |
CXCL5 | Recruits and activates granulocytes and promotes angiogenesis, tumor growth, and metastasis in the tumor microenvironment [23] | ↑(CC) [24,25] | Tumors with exosome-derived CXCL5 use it to facilitate their progression through infiltration of leukocytes in the tumor microenvironment | ↓ |
KIF2A | Required for cell mitosis [26] | ↑(CC) [27] | Rapid mitosis of cancer cells may promote the absorption of KIF2A from exosomes | ↓ |
RGS18 | Negative regulator of G protein-coupled receptors and controls platelet activation and production [28,29] | ↑(OC) [30] | Tumors may absorb RGS18 present in exosomes, which can promote thrombogenesis. The reduction of exosomal RGS18 by tumors may promote activated platelets around the primary tumor, which can facilitate tumor growth and invasion. Therefore, dysregulation of RGS18 can result in tumorigenesis through persistent platelet activation | ↓ |
DAPP1 | Activation of antigen-specific T cells [31] | NA | This may contribute to tumorigenesis through deficiency of tumor-specific immunity | ↓ |
LINC00989 | Decreases with RGS18 in tumor-educated platelets [32] | ↓(PaC) [32] | The two lncRNAs may facilitate platelet activation in cancer patients via targeting RGS18 | ↓ |
LOC105374768 | NA | NA | ↓ | |
SNORD17 | The derived RNA positively correlates with CD8 T cell infiltration in thymoma and stomach cancer [33] | ↑(COC) [34] | Promotion of these snoRNAs present in exosomes may be related to cancer related-lymphopenia | ↑ |
SCARNA12 | NA | ↑(LC) [35] | ↑ | |
SNORA6 | The derived RNA negatively correlates with CD8 T cell infiltration in LGG, PC, pancreatic cancer, and HNC [33] | ↑(PC) [36] | ↑ | |
SNORA12 | NA | ↓(CC) [37] ↑(LC) [35] | ↑ | |
SCARNA1 | NA | ↑(LC) [35] | ↑ | |
SNORD97 | NA | ↓(CC) [37] | Promotion of these snoRNAs present in exosomes may be related to decreased lymphocyte activity | ↑ |
SNORD62 | NA | NA | ↑ | |
SNORD38A | The derived RNA negatively correlates with CD8 T cell infiltration in HNC, LC, TGCT, and PCPG [33] | ↑(COC) [34] | ↑ |
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Cho, O.; Kim, D.-W.; Cheong, J.-Y. Screening Plasma Exosomal RNAs as Diagnostic Markers for Cervical Cancer: An Analysis of Patients Who Underwent Primary Chemoradiotherapy. Biomolecules 2021, 11, 1691. https://doi.org/10.3390/biom11111691
Cho O, Kim D-W, Cheong J-Y. Screening Plasma Exosomal RNAs as Diagnostic Markers for Cervical Cancer: An Analysis of Patients Who Underwent Primary Chemoradiotherapy. Biomolecules. 2021; 11(11):1691. https://doi.org/10.3390/biom11111691
Chicago/Turabian StyleCho, Oyeon, Do-Wan Kim, and Jae-Youn Cheong. 2021. "Screening Plasma Exosomal RNAs as Diagnostic Markers for Cervical Cancer: An Analysis of Patients Who Underwent Primary Chemoradiotherapy" Biomolecules 11, no. 11: 1691. https://doi.org/10.3390/biom11111691