Abstract 4768: Differential expression of triptolide gene targets in human papillomavirus positive and negative head and neck squamous cell carcinomas

Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in the US. HPV represents a more recent risk factor for which treatment may be individualized. HPV expresses viral E6 and E7 oncoproteins which downregulate wild type p53 and Rb respectively. Triptolide, a derivative of a traditional Chinese medicinal herb, has been shown to inhibit viral E6, thereby reactivating wild type p53. Therefore, triptolide may target HPV positive HNSCC as a putative treatment. To explore this, we compared mutation, methylation, and expression of triptolide gene targets between HPV positive and HPV negative samples from The Cancer Genome Atlas (TCGA) program. Patient data was queried from the TCGA PanCancer Atlas for HNSCC using cBioPortal. This included a total of 523 patients with 487 meeting inclusion criteria. 415 patients were HPV (-) and 72 were HPV (+).Differences in direct genomic alterations, DNA methylation, mRNA expression, and protein expression of the 34 known triptolide targets were compared between these two groups using the Benjamini-Hochberg Procedure with a significance level of q < 0.05. Significant differences of the studied genes (q < 0.05) are shown in Table 1. There were no significant differences in protein expression. Of the 34 known triptolide targets, HPV positive and negative samples show variable enrichment. Triptolide targets exhibit greater methylation and mRNA expression in HPV positive samples supporting triptolide’s efficacy in these samples. However, other triptolide targets are the differentially expressed and methylated in HPV negative samples, so the compound may have a beneficial effect in this context as well. Further studies are required to test efficacy of triptolide against HPV positive and HPV negative HNSCC in vitro and in vivo models. Table 1. Significant genomic differences between HPV (+) and HPV (-) samples shown. Enriched in HPV (+) Enriched in HPV (-) Gene Log2 ratio q-value Gene Log2 ratio q-value DNA methylation Direct genomic mutations VEGFA 0 5.85E-03 TP53 3.08 4.53E-29 BCL2 0.07 9.78E-18 DNA methylation JUN 0 4.89E-02 RELA 0.07 5.06E-04 CD80 0.06 2.56E-02 STAT3 0.24 3.19E-20 BIRC3 0.01 1.29E-04 TNF 0.07 4.31E-04 CD274 0.07 4.40E-03 XIAP 0.07 8.02E-06 CCR7 0.11 3.56E-08 CXCR4 0.04 3.58E-03 CD1A 0.10 2.36E-05 CD40 0.06 1.00E-05 C3 0.06 6.91E-03 CD14 0.04 8.12E-03 CD86 0.03 2.45E-02 mRNA expression mRNA expression RELA 0.16 1.90E-03 STAT3 0.25 4.22E-03 CDKN1A 0.28 3.00E-02 BCL2 1.95 1.68E-14 PLAU 1.37 3.24E-12 CASP3 0.45 2.55E-07 CXCL8 1.05 1.51E-04 TP53 1.45 3.16E-25 MCL1 0.23 3.59E-04 IL2 0.52 2.13E-06 TGFB1 0.77 3.27E-11 INFG 1.15 2.08E-05 DEFB4A 1.10 1.77E-02 CXCR4 1.18 8.03E-07 BIRC3 1.20 6.14E-06 IL23A 0.77 3.88E-04 CCR7 1.18 2.10E-06 CD40 0.54 2.27E-04 Citation Format: William E. Kamm, Lindsey J. Mortenson, Frank G. Ondrey. Differential expression of triptolide gene targets in human papillomavirus positive and negative head and neck squamous cell carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4768.