Association Between Glycosyltransferase Expression and Survival in Head and Neck Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Head and neck cancer is the sixth most common tumor type worldwide, but despite advances in treatment, the 5-year survival rate is only ∼50%. Glycosylation, a common post-translational modification, is frequently altered in cancer. Changes in glycosyltransferase expression in cancer are associated with cellular invasion, tumor growth, and metastasis. However, the role of glycosyltransferase expression in head and neck cancer survival is poorly understood. Here, we examine the association between glycosyltransferase expression and survival in head and neck squamous cell carcinoma (HNSCC). <h3>Materials/Methods</h3> A retrospective cohort study was performed with data from the Cancer Genome Atlas (TCGA) HNSCC dataset (n=499), containing expression (mRNA) level data, generated via high-throughput sequencing, of primary tumor tissue from patients with a diagnosis of HNSCC (deidentified). A set of glycosyltransferase genes: FUT1-FUT11, POFUT1-2, ST3Gal1-6, ST6Gal1-2, ST6GalNac1-6, ST8Sia1-6, GALNT2-3, C1GALT1, B4GALT4, GCNT2 were considered. Median expression was used to delineate high and low expression groups. Univariate Kaplan-Meier analyses and logrank tests were conducted. Multivariate analyses were performed via Cox proportional hazards regression to adjust for covariates (HPV status, age at initial diagnosis, sex, alcohol history, tobacco usage, and primary site). <h3>Results</h3> Based on the Kaplan-Meier analysis of FUT2, the median survival time (MST) of the high FUT2-expressing group was 4.7 years, while low expression was associated with an MST of 2.7 years. Cox regression analysis yielded adjusted hazard ratio (aHR) of 0.72 (CI = 0.54-0.95). The MST of the FUT6 high expression group was 4.7 years versus 2.9 years for low expression, with an aHR of 0.62 (CI = 0.47-0.83). The MST of the high-FUT7 expressing group was 4.7 years versus 3.5 years for the low level group, with an aHR of 0.72 (CI = 0.54-0.95). GALNT3 showed the opposite effect, with high expression yielding an MST of 3.1 years versus 4.9 years for the low-expressing group, with aHR of 1.47 (1.11-1.95). An aHR of <1 indicates a protective effect from high expression. <h3>Conclusion</h3> Overexpression of FUT2, FUT6, and FUT7 were associated with increased overall survival, while overexpression of GALNT3 was associated with decreased overall survival in HNSCC. FUT2 is expressed in endoderm-derived epithelial tissue including the digestive tract and salivary glands, while FUT6 and FUT7 are prominently expressed in immune cells. Thus, FUT6 and FUT7 expression may indicate immune cell infiltration into tumor tissue. Future studies will seek to sort tumor tissue based on cell type, to gain a better understanding of the cell-type specific glycosyltransferase expression in HNSCC tumors. The glycosyltransferase genes associated with survival in this study may serve as future drug targets in head and neck cancer.