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Variation in lymphovascular invasion associated genes reflects nodal stage differences in oral squamous cell carcinoma
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DOI：10.1007/s12672-026-05754-y.png)
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Abstract
En 中文
Lymphovascular invasion (LVI) is a critical prognostic factor in oral squamous cell carcinoma (OSCC), however its molecular mechanisms remain poorly defined. This study aimed to identify somatic mutations and mRNA expression profiles associated with LVI and nodal metastasis in OSCC. Analysis of whole-exome sequencing (WES) data from LVI-positive and LVI-negative OSCC tumors in our institutional cohort was conducted, and findings were integrated with WES and RNA sequencing data from The Cancer Genome Atlas and GSE41613 datasets. Patients were stratified by pathologic N stage (pN0, pN1, pN2) and findings were validated. Nine LVI associated genes were identified across nodal stages. PCDHA9, SLC2A3, SEC31B, KIF13B, TRPM4, and RANBP2 were associated with pN2 status, NF1 with pN1, and CPT1A and ATP1A2 with pN0. All nine genes demonstrated prognostic relevance, based on either DNA mutation or RNA expression, in independent validation cohorts. Gene set enrichment analysis identified pathways including mitotic spindle, MYC targets, mTORC1 signaling, and interferon response. Immune deconvolution analysis showed higher CD8 + T cells and T follicular helper (Tfh) cells in LVI-positive tumors at pN0, with reduced CD8 + T cells, Tfh cells, and M1 macrophages at pN2. These findings suggest that LVI-associated molecular features vary across nodal stages and may provide hypothesis-generating insight into metastatic progression in OSCC. Further functional validation is required to confirm their biological relevance.
Keywords:
Oral squamous cell carcinoma
Lymphovascular invasion
Nodal stage
Whole exome sequencing
mRNA expression
Prognosis
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