Exploring the Diagnostic and Predictive Value of Oral Microbiome in Esophageal Cancer: A Systematic Review and Meta-Analysis
Abstract
1. Introduction
2. Methods
2.1. Literature Search
2.2. Study Selection
2.3. Data Extraction
2.4. Meta-Analysis
2.5. Quality Assessment
3. Results
3.1. Literature Search and Study Selection
3.2. Study Characteristics
3.3. Sample Collection
3.4. Alpha-Diversity and Beta-Diversity
3.5. Microbiome Changes in Esophageal Cancer Patients Compared to Healthy Controls
3.6. Meta-Analysis of Microbiome-Based Risk Prediction for ESCC
3.7. Quality Assessment of the Included Studies
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AUC | area under the curve |
CASP | Critical Appraisal Skills Program |
CIs | confidence intervals |
EC | esophageal cancer |
EAC | esophageal adenocarcinoma |
ESCC | esophageal squamous cell carcinoma |
GERD | gastroesophageal reflux disease |
LEfSe | Linear discriminant analysis effect size |
ORs | odds ratios |
OTU | operational taxonomic unit |
PRISMA | Reporting Items for Systematic Reviews and Meta-Analyses |
PROSPERO | International Prospective Register of Systematic Reviews |
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Component | Description |
---|---|
P (Population) | Patients diagnosed with esophageal cancer (including ESCC and EAC) as well as healthy controls. |
I (Intervention/Exposure) | Analysis of oral microbiota composition, primarily via 16S rRNA gene sequencing from saliva or other oral samples (e.g., oral swabs, tongue coating). |
C (Comparison) | Comparison of oral microbiome profiles between esophageal cancer patients and healthy controls. |
O (Outcome) | Differences in microbial diversity (alpha- and beta- diversity), abundance of specific taxa, and diagnostic performance metrics such as sensitivity, specificity, and odds ratios for microbial biomarkers. |
First Author | Year | Country | Study Design | Cancer Type | Participants (Case/Control) | Sex (Male %) (Case/Control) | Age (Case/Control) | Reference |
---|---|---|---|---|---|---|---|---|
Chen, X. | 2015 | China | Case–control study | ESCC | 87/85 | 67.82/72.94 | 64.8/66 a | [29] |
Peters, B.A. | 2017 | USA | Nested case–control study | EAC and ESCC | EAC: 81/160, ESCC: 25/50 | EAC: 92.6/92.5, ESCC: 40/40 | EAC: 68.0/62.4 a ESCC: 66.6/66.8 a | [27] |
Wang, Q. | 2019 | China | Case–control study | ESCC | 20/21 | 70.0/57.14 | 65.9/65.14 a | [24] |
Kageyama, S. | 2019 | Japan | Case–control study | Esophageal cancer | 12/118 | 66.7/71.2 | 68.4/66.4 a | [30] |
Liu, F. | 2020 | China | Nested case–control study | ESCC | 84/168 | 52.38/52.38 | 57/56 b | [31] |
Zhao, Q. | 2020 | China | Case–control study | Esophageal cancer | 39/51 | 59.0/45.1 | 60.39/49.18 a | [32] |
Chen, M. F. | 2021 | Taiwan | Case–control study | ESCC | 34/18 | // | // | [23] |
Li, H. | 2021 | China | Case–control study | ESCC | 33/35 | 84.9/65.7 | 66/61 b | [33] |
Li, Z. | 2021 | China | Case–control study | ESCC | 70/82 | 65.7/58.5 | 63.64/58.51 a | [34] |
Wei, J. | 2022 | China | Case–control study | ESCC | 178/101 | 78.09/49.50 | Screening: 61.71/43.90 a, Verification: 61.41/44.45 a | [35] |
Xiao, P. | 2022 | China | Case–control study | Esophageal Precancerous Lesions | 123/176 | 57.7/54.5 | 59.71/58.99 a | [36] |
Chen, X. | 2022 | China | Case–control study | ESCC | 90/50 | 78.89/54.00 | 60.8/47.7 a | [37] |
Hao, Y. | 2022 | USA | Case–control study | EAC | 19/27 | 94.74/62.96 | 59.9/56.3 a | [38] |
Jiang, Z. | 2023 | China | Case–control study | ESCC | 56/53 | 53.57/49.06 | 54.56/49.32 a | [39] |
Chen, H. | 2024 | China | Case–control study | Early-stage intramucosal ESCC | 31/21 | 61.3/52.4 | 70/64 b | [40] |
Li, M. | 2024 | China | Case–control study | ESCC | 52/52 | // | // | [41] |
Solfisburg, Q.S. | 2024 | USA | Case–control study | EAC | 78/125 | 79.49/36.00 | 65/50 b | [42] |
He, Y. | 2024 | China | Case–control study | ESCC | Before: 79/10, After: 8/10 | Before: 74.6/50.0, After: 50.0/50.0 | Before: 72/70 b After: 75/70 b | [43] |
First Author | Year | Sample Type | 16S Region | Sequencing Platform | Reference |
---|---|---|---|---|---|
Chen, X. | 2015 | Saliva | V3–V4 | 454 Roche FLX Titanium adapters (454 Life Sciences, Branford, CT, USA) | [29] |
Peters, B.A. | 2017 | Oral wash | V4 | Illumina MiSeq (-) | [27] |
Wang, Q. | 2019 | Saliva | V3–V4 | Illumina MiSeq (Illumina, San Diago, CA, USA) | [24] |
Kageyama, S. | 2019 | Saliva | V1–V2 | Ion PGM Hi-Q view (Thermo Fisher Scientific, Waltham, MA, USA) | [30] |
Liu, F. | 2020 | Oral swabs | V3–V4 | Ion S5 XL (Thermo Fisher Scientific, Waltham, MA, USA) | [31] |
Zhao, Q. | 2020 | Saliva | V3–V4 | Illumina MiSeq PE250 (Illumina, San Diago, CA, USA) | [32] |
Chen, M. F. | 2021 | Oral biofilms | Not reported | Illumina MiSeq (Illumina, San Diago, CA, USA) | [23] |
Li, H. | 2021 | Saliva | V3–V4 | Illumina MiSeq 2×300 bp (Illumina, San Diago, CA, USA) | [33] |
Li, Z. | 2021 | Saliva | V4 | Ion S5TM XL (Thermo Fisher Scientific, MA, USA) | [34] |
Wei, J. | 2022 | Saliva | V4 | Illumina HiSeq 2500 (Illumina, San Diago, CA, USA) | [35] |
Xiao, P. | 2022 | Tongue coating | V3–V4 | Illumina MiSeq PE (Illumina, San Diago, CA, USA) | [36] |
Chen, X. | 2022 | Saliva | V4 | Illumina HiSeq2500 (Illumina, San Diago, CA, USA) | [37] |
Hao, Y. | 2022 | Buccal mucosa | V3–V5 | Not reported | [38] |
Jiang, Z. | 2023 | Oral swabs | V3–V4 | Illumina NovaSeq6000 PE250 (Illumina, San Diago, CA, USA) | [39] |
Chen, H. | 2024 | Saliva | V3–V4 | Illumina NovaSeq (Illumina, San Diago, CA, USA) | [40] |
Li, M. | 2024 | Saliva | V4 | Illumina MiniSeq (Illumina, San Diago, CA, USA) | [41] |
Solfisburg, Q.S. | 2024 | Saliva | V3–V4 | Illumina MiSeq (Illumina, San Diago, CA, USA) | [42] |
He, Y. | 2024 | Saliva | V3–V4 | Illumina NovaSeq 6000 (Illumina, San Diago, CA, USA) | [43] |
First Author | Alpha Diversity | Beta Diversity | Reference |
---|---|---|---|
Chen, X. | ↓ Shannon (3.7 → 3.4), Chao1 (147.2 → 120.8) | Significant (p < 0.05, UniFrac) | [29] |
Peters, B.A. | Not significant | Not significant (UniFrac) | [27] |
Wang, Q. | Not significant | Significant (p = 0.037, Bray-Curtis) | [24] |
Kageyama, S. | ↑ Shannon (~3.4 → ~3.6), Chao1 (~200 → ~220) | Significant (p = 0.01, UniFrac) | [30] |
Liu, F. | ↑ Shannon | Not significant (UniFrac) | [31] |
Zhao, Q. | Not significant | Significant (p = 0.001, Bray-Curtis) | [32] |
Chen, M. F. | ↑ Shannon | Significant (p = 0.001) | [23] |
Li, H. | Not significant | Unweighted: significant (p = 0.001), Weighted: not significant | [33] |
Li, Z. | ↓ Shannon (~6.1 → ~5.8) | Significant (p = 0.001, Bray-Curtis) | [34] |
Wei, J. | ↑ S. salivarius, etc. (no Shannon shown) | Not reported | [35] |
Xiao, P. | Not significant | Not reported | [36] |
Chen, X. | ↑ Shannon | Not significant | [37] |
Hao, Y. | ↑ Shannon | Significant (p < 0.01, UniFrac) | [38] |
Jiang, Z. | Not significant | Significant (p < 0.05) | [39] |
Chen, H. | Not significant | Not significant (Bray-Curtis) | [40] |
Li, M. | Not significant | Significant (p < 0.01, UniFrac) | [41] |
Solfisburg, Q.S. | ↓ Shannon, ↓ Simpson | Significant (p < 0.01, UniFrac) | [42] |
He, Y. | ↓ Chao1 | Significant (Bray-Curtis) | [43] |
First Author | Key Microbial Changes | Potential Biomarkers | Sensitivity/Specificity | Notes | Reference | |
---|---|---|---|---|---|---|
Genus | Species | |||||
Chen, X. | Prevotella (↑), Streptococcus (↑), Porphyromonas (↑); Lautropia (↓), Corynebacterium (↓) | - | Prevotella, Streptococcus, Porphyromonas | Not reported | First ESCC saliva study; 454 sequencing | [29] |
Peters, B.A. | - | Porphyromonas gingivalis (↑), Prevotella nanceiensis (↑), Treponema vincentii (↑) | Porphyromonas gingivalis, Prevotella nanceiensis | Not reported | ESCC and EAC separation | [27] |
Wang, Q. | Actinomyces (↑), Atopobium (↑); Fusobacterium (↓), Porphyromonas (↓) | - | Actinomyces, Atopobium | Not reported | Small sample; diversity not significant | [24] |
Kageyama, S. | - | Porphyromonas gingivalis (↑), Fusobacterium nucleatum subsp. vincentii (↑) | Porphyromonas gingivalis, Fusobacterium nucleatum | Not reported | OTU-rich profile in EC | [30] |
Liu, F. | - | Fusobacterium nucleatum (↑), Actinomyces naeslundii (↑), Prevotella intermedia (↑), Treponema vincentii (↑) | Fusobacterium nucleatum, Actinomyces naeslundii | Not reported | Enriched taxa profiled | [31] |
Zhao, Q. | Prevotella (↑); Neisseria (↓) | - | Prevotella, Neisseria | Not reported | Clear Prevotella ↑/Neisseria ↓ pattern | [32] |
Chen, M. F. | - | Porphyromonas gingivalis (↑), Veillonella parvula (↑) | Porphyromonas gingivalis, Veillonella parvula | Not reported | Clinical + mechanistic focus | [23] |
Li, H. | Streptococcus (↑), Prevotella_7 (↑); Neisseria (↓) | - | Streptococcus, Prevotella_7 * | Not reported | Diversity mixed; taxa significant | [33] |
Li, Z. | Parvimonas (↑), Helicobacter (↑), Peptostreptococcus (↑) | - | Parvimonas, Helicobacter | Not reported | Disease progression correlated | [34] |
Wei, J. | - | Streptococcus salivarius (↑), Fusobacterium nucleatum (↑), Porphyromonas gingivalis (↑) | Streptococcus salivarius, Fusobacterium nucleatum, Porphyromonas gingivalis | 69.3–86.4%/58.8–96.1% | qPCR validation used | [35] |
Xiao, P. | Capnocytophaga (↑); Atopobium (↓), Hydrobacter (↓) | Eubacterium yurii (↑) | Eubacterium yurii, Capnocytophaga | Not reported | Focused on pre-cancerous lesion comparison | [36] |
Chen, X. | Leptotrichia (↑), Porphyromonas (↑) | - | Leptotrichia, Porphyromonas | 68.2–86.4%/64.4–86.0% | V4 analysis; genus-level resolution | [37] |
Hao, Y. | - | Actinomyces bowdenii (↑), Atopobium parvulum (↑) | Actinomyces bowdenii, Atopobium parvulum | Not reported | Staged analysis with species detail | [38] |
Jiang, Z. | Leptotrichia (↑) | - | Leptotrichia | Not reported | Genus-focused significant taxa | [39] |
Chen, H. | Shigella (↑), Leptotrichia (↑) | Porphyromonas endodontalis (↑) | Porphyromonas endodontalis, Leptotrichia | Not reported | Species-level marker clarity | [40] |
Li, M. | - | Prevotella histicola (↑), Fusobacterium nucleatum (↑), Prevotella intermedia (↑) | Prevotella spp., Fusobacterium nucleatum | Not reported | Expanded Prevotella panel | [41] |
Solfisburg, Q.S. | Streptococcus spp. (↑) | - | Streptococcus spp. | Not reported | Dysplasia stratification | [42] |
He, Y. | Veillonellaceae (↑) | Prevotella salivae (↑) | Prevotella salivae, Veillonellaceae | Not reported | Pre-/post-treatment comparison | [43] |
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Chen, J.-C.; Hsu, M.-H.; Hu, S.-W.; Lin, Y.-Y. Exploring the Diagnostic and Predictive Value of Oral Microbiome in Esophageal Cancer: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2025, 26, 9457. https://doi.org/10.3390/ijms26199457
Chen J-C, Hsu M-H, Hu S-W, Lin Y-Y. Exploring the Diagnostic and Predictive Value of Oral Microbiome in Esophageal Cancer: A Systematic Review and Meta-Analysis. International Journal of Molecular Sciences. 2025; 26(19):9457. https://doi.org/10.3390/ijms26199457
Chicago/Turabian StyleChen, Jie-Chi, Min-Hsun Hsu, Suh-Woan Hu, and Yuh-Yih Lin. 2025. "Exploring the Diagnostic and Predictive Value of Oral Microbiome in Esophageal Cancer: A Systematic Review and Meta-Analysis" International Journal of Molecular Sciences 26, no. 19: 9457. https://doi.org/10.3390/ijms26199457
APA StyleChen, J.-C., Hsu, M.-H., Hu, S.-W., & Lin, Y.-Y. (2025). Exploring the Diagnostic and Predictive Value of Oral Microbiome in Esophageal Cancer: A Systematic Review and Meta-Analysis. International Journal of Molecular Sciences, 26(19), 9457. https://doi.org/10.3390/ijms26199457