A comprehensive transcriptome based meta-analysis to unveil the aggression nexus of oral squamous cell carcinoma
Lymph node metastasis in oral cancer (OC) complicates management due to its aggressive nature and high risk of recurrence, underscoring the need for biomarkers for early detection and targeted therapies. However, the drivers of this aggressive phenotype remain unclear due to the variability in gene...
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Elsevier
2025-06-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825000883 |
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| author | Soujanya J. Vastrad Ganesan Rajalekshmi Saraswathy Jagadish B. Dasari Gouri Nair Ashok Madarakhandi Dominic Augustine S.V. Sowmya |
| author_facet | Soujanya J. Vastrad Ganesan Rajalekshmi Saraswathy Jagadish B. Dasari Gouri Nair Ashok Madarakhandi Dominic Augustine S.V. Sowmya |
| author_sort | Soujanya J. Vastrad |
| collection | DOAJ |
| description | Lymph node metastasis in oral cancer (OC) complicates management due to its aggressive nature and high risk of recurrence, underscoring the need for biomarkers for early detection and targeted therapies. However, the drivers of this aggressive phenotype remain unclear due to the variability in gene expression patterns. To address this, an integrative meta-analysis of six publicly available transcriptomic profiles, categorized by lymph nodal status, is conducted. Key determinants of disease progression are identified through functional characterization and the TopConfects ranking approach of nodal associated differentially expressed genes (DEGs). To explore the critical nexus between lymph node metastasis and OC recurrence, significant metastatic genes were cross-analysed with literature-derived genes exhibiting aberrant methylation patterns in OC recurrence. Their clinical relevance and expression patterns were then validated in an external dataset from the TCGA head and neck cancer cohort. The analysis identified elevated expression of genes involved in extracellular matrix remodelling and immune response, while the expression of genes related to cellular differentiation and barrier functions was reduced, driving the transition to nodal positivity. The highest-ranked gene, MMP1, showed a log-fold change (LFC) of 4.946 (95 % CI: 3.71, 6.18) in nodal-negative samples, which increased to 5.899 (95 % CI: 4.80, 6.99) in nodal-positive samples, indicating consistent elevation across disease stages. In contrast, TMPRSS11B was significantly downregulated, with an LFC of −5.512 (95 % CI: −6.63, −4.38) in nodal-negative samples and −5.898 (95 % CI: −7.15, −4.64) in nodal-positive samples. Furthermore, MEIS1, down-regulated in nodal-positive status, was found to exhibit hypermethylation at CpG sites associated with OC recurrence. This study represents the first transcriptomic meta-analysis to explore the intersection of lymph node metastasis and OC recurrence, identifying MEIS1 as a potential key contributor. These comprehensive insights into disease trajectories offer potential biomarkers and therapeutic targets for future treatment strategies. |
| format | Article |
| id | doaj-art-7b1d4931b7a74124b112129ee6c84cee |
| institution | DOAJ |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-7b1d4931b7a74124b112129ee6c84cee2025-08-20T03:22:35ZengElsevierBiochemistry and Biophysics Reports2405-58082025-06-014210200110.1016/j.bbrep.2025.102001A comprehensive transcriptome based meta-analysis to unveil the aggression nexus of oral squamous cell carcinomaSoujanya J. Vastrad0Ganesan Rajalekshmi Saraswathy1Jagadish B. Dasari2Gouri Nair3Ashok Madarakhandi4Dominic Augustine5S.V. Sowmya6Department of Pharmacy Practice, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, New BEL Road, M.S.R. Nagar, Bengaluru, IndiaDepartment of Pharmacy Practice, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, New BEL Road, M.S.R. Nagar, Bengaluru, India; Corresponding author.Department of Biology, University of Rome Tor Vergata, Rome, ItalyDepartment of Pharmacology, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bangalore, Karnataka, IndiaDepartment of Pharmaceutical Chemistry, KLE College of Pharmacy, (A Constituent Unit of KAHER-Belagavi), 2nd Block, Rajajinagar, Bangalore, IndiaDepartment of Oral Pathology and Microbiology, Faculty of Dental Sciences, M.S. Ramaiah University of Applied Sciences, New BEL Road, M.S.R. Nagar, Bengaluru, IndiaDepartment of Oral Pathology and Microbiology, Faculty of Dental Sciences, M.S. Ramaiah University of Applied Sciences, New BEL Road, M.S.R. Nagar, Bengaluru, IndiaLymph node metastasis in oral cancer (OC) complicates management due to its aggressive nature and high risk of recurrence, underscoring the need for biomarkers for early detection and targeted therapies. However, the drivers of this aggressive phenotype remain unclear due to the variability in gene expression patterns. To address this, an integrative meta-analysis of six publicly available transcriptomic profiles, categorized by lymph nodal status, is conducted. Key determinants of disease progression are identified through functional characterization and the TopConfects ranking approach of nodal associated differentially expressed genes (DEGs). To explore the critical nexus between lymph node metastasis and OC recurrence, significant metastatic genes were cross-analysed with literature-derived genes exhibiting aberrant methylation patterns in OC recurrence. Their clinical relevance and expression patterns were then validated in an external dataset from the TCGA head and neck cancer cohort. The analysis identified elevated expression of genes involved in extracellular matrix remodelling and immune response, while the expression of genes related to cellular differentiation and barrier functions was reduced, driving the transition to nodal positivity. The highest-ranked gene, MMP1, showed a log-fold change (LFC) of 4.946 (95 % CI: 3.71, 6.18) in nodal-negative samples, which increased to 5.899 (95 % CI: 4.80, 6.99) in nodal-positive samples, indicating consistent elevation across disease stages. In contrast, TMPRSS11B was significantly downregulated, with an LFC of −5.512 (95 % CI: −6.63, −4.38) in nodal-negative samples and −5.898 (95 % CI: −7.15, −4.64) in nodal-positive samples. Furthermore, MEIS1, down-regulated in nodal-positive status, was found to exhibit hypermethylation at CpG sites associated with OC recurrence. This study represents the first transcriptomic meta-analysis to explore the intersection of lymph node metastasis and OC recurrence, identifying MEIS1 as a potential key contributor. These comprehensive insights into disease trajectories offer potential biomarkers and therapeutic targets for future treatment strategies.http://www.sciencedirect.com/science/article/pii/S2405580825000883Oral cancerNodal metastasisRecurrenceTranscriptomic meta-analysisBiomarkersGenomics |
| spellingShingle | Soujanya J. Vastrad Ganesan Rajalekshmi Saraswathy Jagadish B. Dasari Gouri Nair Ashok Madarakhandi Dominic Augustine S.V. Sowmya A comprehensive transcriptome based meta-analysis to unveil the aggression nexus of oral squamous cell carcinoma Biochemistry and Biophysics Reports Oral cancer Nodal metastasis Recurrence Transcriptomic meta-analysis Biomarkers Genomics |
| title | A comprehensive transcriptome based meta-analysis to unveil the aggression nexus of oral squamous cell carcinoma |
| title_full | A comprehensive transcriptome based meta-analysis to unveil the aggression nexus of oral squamous cell carcinoma |
| title_fullStr | A comprehensive transcriptome based meta-analysis to unveil the aggression nexus of oral squamous cell carcinoma |
| title_full_unstemmed | A comprehensive transcriptome based meta-analysis to unveil the aggression nexus of oral squamous cell carcinoma |
| title_short | A comprehensive transcriptome based meta-analysis to unveil the aggression nexus of oral squamous cell carcinoma |
| title_sort | comprehensive transcriptome based meta analysis to unveil the aggression nexus of oral squamous cell carcinoma |
| topic | Oral cancer Nodal metastasis Recurrence Transcriptomic meta-analysis Biomarkers Genomics |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825000883 |
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