CNV Analysis of the Correlation between Preoperative Lymph Node Metastasis and Prognosis of Early Tongue Cancer

Objective: To investigate the relationship between preoperative concealed lymph node metastasis (LNM) and prognosis in patients with early tongue cancer. Methods: According to preoperative lymph node dissection, 41 patients with tongue cancer were divided into the LNM group (n=19) and the non-LNM group (n=22). Analysis of single nucleotide variation (SNV), tumor mutation burden (TMB), mutant allele tumor heterogeneity (MATH), aneuploidy and copy number variation (CNV) was performed to identify differentially expressed genes (DEGs) related to LNM. While KEGG analysis was conducted to reveal the CNV differentially expressed genes and main enriched pathways, the correlation between pathways and genes was analyzed by hierarchical clustering. The clinical information of LNM and data on overall survival (OS) rate were obtained from The Cancer Genome Atlas (TCGA), and survival analysis was performed based on combined LNM information. Results: We observed significant correlations for the mTOR signaling pathway, Hippo signaling pathway and Wnt signaling pathway with the LNM group, while leukocyte transendothelial migration and cytokine-cytokine receptor interaction were markedly correlated with the non-LNM group. Moreover, TNFRSF10C was identified as the main DEG in the leukocyte transendothelial migration pathway. TCGA-based validation revealed that the disease-free survival (DFS) of the non-LNM group was significantly higher than that of the LNM group (P<0.005) when TNFRSF10C CNV was set to a log2 ratio>-0.163. Conclusion: The differential expression of TNFRSF10C in leukocyte transendothelial migration, an immune-related pathway, is associated with LNM and DFS. The TNFRSF10C CNV log2 ratio could potentially serve as an indicator of good prognosis for tongue cancer patients with non-LNM after neck dissection.