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Author
Prasidda Khadka -
Discovery PI
Paul Boutros
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Project Co-Author
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Abstract Title
Genomic analysis of lymph node evolution in head and neck squamous cell carcinomas
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Discovery AOC Petal or Dual Degree Program
Basic, Clinical, & Translational Research
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Abstract
Title: Genomic analysis of lymph node evolution in head and neck squamous cell carcinomas
Author: Prasidda Khadka, Paul Boutros
Area of Concentration (Petal): BCTR
Specialty (if any): Cancer genomics
Keywords: Head and neck cancer, genomics, cancer evolution
Background: Accurate characterization of regional lymph node involvement in Head and Neck Squamous Cell Carcinomas (HNSC) is critical for staging. However, temporal pattern of lymph node evolution in HNSC is not well understood. Two potential routes of lymph node spread from the primary tumor include parallel (lower and higher tiers of lymph nodes seeded at the same time) and sequential (first tier lymph nodes seeded first followed sequentially by higher tiers).
Objective: To characterize transcriptomic differences between node positive vs node negative HNSC to gain further insight into genomic evolution of HNSC.
Methods: We compared the transcriptomic profiles of node positive vs node negative HNSC from the publicly available TCGA-HNSC dataset. STAR gene counts were downloaded from GDC portal using TCGAbiolinks. These counts were used for downstream analysis using DESeq2 pipeline. Pathway enrichment analysis was performed using GO and GSEA.
Results: Overall, we found 370 genes to be differentially expressed between node positive vs node negative tumors (|LFC|>1 and adjusted p-value<0.1). In particular, genes belonging to the FGF signaling pathways (FGF3, FGF4, FGF19, FGF23) were significantly upregulated in node positive samples compared to node negative samples. Furthermore, GSEA revealed 11/50 hallmark gene sets, including epithelial to mesenchymal transition (EMT) gene set, to be significantly enriched (FDR<0.1) in node positive tumors.
Conclusions: There are transcriptomic differences between node positive vs negative HNSC. This suggests that there are differences in gene expression that can predict nodal status of HNSC. Correlation of these findings with proteomics and methylation analyses will be important to further delineate differences based on nodal status.