Periodontitis-Associated Transcriptional Signatures and Their Correspondence with Oral Mucosal Responses to Radiotherapy: A Cross-Cohort Analysis
- 1Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou Avenue, Guangzhou 510515, China
- 2Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
- 3Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
Abstract
The extent to which periodontitis-associated transcriptional patterns correspond to oral mucosal responses to radiotherapy remains unclear. We integrated three human transcriptomic cohorts to characterize this correspondence and its analytical stability using differential-expression, signature-score, and gene-set analyses. In GSE10334, a patient-blocked analysis of 247 gingival profiles identified 111 differentially expressed genes, of which 104 retained significance across sensitivity analyses. In the independent GSE173078 cohort, 95 of 97 mapped genes showed concordant effect directions (Spearman ρ = 0.824). Twenty-three genes met replication criteria in the fully adjusted model, compared with none in the batch-only model. The signature score was higher in periodontitis than in healthy gingiva (β = 1.66; 95% confidence interval, 0.40–2.93). In GSE103412, comprising eight patients with seven post-treatment observations, neither the 18 mapped replicated periodontal genes nor longitudinal signature scores met significance criteria. CAMERA detected enrichment of the periodontitis-upregulated set during and after radiotherapy with intergene correlation fixed at 0.01 (false discovery rate [FDR] = 0.00124 and 4.70 × 10−6), but not with data-estimated correlation (FDR = 0.360 and 0.177). Expression-matched random-set comparisons indicated signals exceeding the specified background without establishing disease specificity. Twenty-one overlapping Gene Ontology terms showed concordant cross-cohort enrichment under the original analytical specification. Cellular-proxy analyses suggested contributions from tissue composition or cellular state, while exploratory associations with mucositis severity were nonsignificant after correction. These findings identify partial, analytically dependent transcriptional correspondence without establishing that periodontitis increases susceptibility to radiation-induced mucositis or provides clinical predictive value. Prospective studies incorporating periodontal assessment and concurrent molecular and clinical measurements are needed.
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BibTeX
@article{liu2026periodontitisassociated,
title = {{Periodontitis-Associated Transcriptional Signatures and Their Correspondence with Oral Mucosal Responses to Radiotherapy: A Cross-Cohort Analysis}},
author = {Ziqiang Liu and Ronghan Huang and Feiyuan Xue and Xiaodan Feng and Shichun Gao and Zhendong Gong and Lin Liu and Runting Wang and Yanni Wu and Guozhu Xie and Lanfang Zhang},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219976},
url = {https://www.mdpi.com/1422-0067/27/21/9976},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Periodontitis-Associated Transcriptional Signatures and Their Correspondence with Oral Mucosal Responses to Radiotherapy: A Cross-Cohort Analysis
AU - Ziqiang Liu
AU - Ronghan Huang
AU - Feiyuan Xue
AU - Xiaodan Feng
AU - Shichun Gao
AU - Zhendong Gong
AU - Lin Liu
AU - Runting Wang
AU - Yanni Wu
AU - Guozhu Xie
AU - Lanfang Zhang
PY - 2026
DA - 2026/11/07
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219976
UR - https://www.mdpi.com/1422-0067/27/21/9976
AB - The extent to which periodontitis-associated transcriptional patterns correspond to oral mucosal responses to radiotherapy remains unclear. We integrated three human transcriptomic cohorts to characterize this correspondence and its analytical stability using differential-expression, signature-score, and gene-set analyses. In GSE10334, a patient-blocked analysis of 247 gingival profiles identified 111 differentially expressed genes, of which 104 retained significance across sensitivity analyses. In the independent GSE173078 cohort, 95 of 97 mapped genes showed concordant effect directions (Spearman ρ = 0.824). Twenty-three genes met replication criteria in the fully adjusted model, compared with none in the batch-only model. The signature score was higher in periodontitis than in healthy gingiva (β = 1.66; 95% confidence interval, 0.40–2.93). In GSE103412, comprising eight patients with seven post-treatment observations, neither the 18 mapped replicated periodontal genes nor longitudinal signature scores met significance criteria. CAMERA detected enrichment of the periodontitis-upregulated set during and after radiotherapy with intergene correlation fixed at 0.01 (false discovery rate [FDR] = 0.00124 and 4.70 × 10−6), but not with data-estimated correlation (FDR = 0.360 and 0.177). Expression-matched random-set comparisons indicated signals exceeding the specified background without establishing disease specificity. Twenty-one overlapping Gene Ontology terms showed concordant cross-cohort enrichment under the original analytical specification. Cellular-proxy analyses suggested contributions from tissue composition or cellular state, while exploratory associations with mucositis severity were nonsignificant after correction. These findings identify partial, analytically dependent transcriptional correspondence without establishing that periodontitis increases susceptibility to radiation-induced mucositis or provides clinical predictive value. Prospective studies incorporating periodontal assessment and concurrent molecular and clinical measurements are needed.
SN - 1422-0067
ER -