Alexander Philipe Maas (Bonn), Melina Rücker (Bonn), Simon Fietz (Bonn), Luka de Vos-Hillebrand (Bonn), Joëlle Cäcilia Mischer (Bonn), Sebastian Strieth (Bonn), Dimo Dietrich (Bonn)
Introduction:
Androgen-inducible gene 1 (AIG1), located in cytogenic band 6q24.2, encodes for a hydrophobic protein highly expressed in liver tissue. AIG1 overexpressing cells show increased nuclear factor of activated T cells (NFAT) dependent gene transcription, suggesting a role of AIG1 in oncogenesis and lymphocyte activation. Further, AIG1 interacts with Pirh2, which ubiquitylates p53, leading to its proteasomal degradation. In hepatocellular carcinoma AIG1 expression positively correlates with survival.
Material and methods:
We analyzed mRNA expression data obtained from bulk tumor samples of head and neck squamous cell carcinoma (HNSCC) patients (N = 499) from The Cancer Genome Atlas (TCGA). Survival analyses were performed to investigate the prognostic value of AIG1 mRNA expression in human papillomavirus (HPV)-positive and -negative HNSCC. We analyzed immune cell signatures and tumor-infiltrating leukocyte fraction of the TCGA samples with regard to AIG1 expression. Correlative analyses were performed to identify co-expressed genes. Single cell mRNA sequencing data of tongue tissue was analyzed to examine AIG1 expression levels in normal tissue of the oral cavity.
Results:
Higher AIG1 mRNA expression was associated with unfavorable overall survival in HPV-negative as well as in HPV-positive HNSCC. Correlation analysis revealed a significant positive correlation of AIG1 mRNA expression with genes located on chromosome 6q21-27. In tongue tissue AIG1 mRNA is highly expressed in suprabasal keratinocytes.
Discussion:
AIG1 is a prognostic biomarker in HNSCC independent of HPV-status, having high AIG1 mRNA levels correlating negatively with overall survival. Deletion of chromosome 6q21-27 might impact HNSCC tumors biologically.
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