AUTHOR=Feng Yao , Zhou Ying-Hui , Zhao Jie , Su Xiao-Lin , Chen Ning-Xin , Zhao Ya-Qiong , Ye Qin , Hu Jing , Ou-Yang Ze-Yue , Zhong Meng-Mei , Yang Yi-Fan , Han Peng-Ju , Guo Yue , Feng Yun-Zhi 

TITLE=Prognostic biomarker GSTK1 in head and neck squamous cell carcinoma and its correlation with immune infiltration and DNA methylation

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1041042

DOI=10.3389/fgene.2023.1041042

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Glutathione S-transferase kappa 1 (GSTK1) is critical in sarcoma and breast cancer (BRCA) development. However, the clinical significance of GSTK1 in head and neck squamous cell carcinoma (HNSC) remains unclear. This study is the first investigation into the role of GSTK1 in HNSC.</p><p><bold>Methods:</bold> All original data were downloaded from the Cancer Genome Atlas (TCGA) dataset and verified by R Base Package 4.2.0. The expression of GSTK1 in various cancers was explored with TIMER and TCGA databases. Prognostic value of GSTK1 was analyzed <italic>via</italic> survival module of Kaplan-Meier plotter and Human Protein Atlas database and Cox regression analysis. The association between GSTK1 and clinical features was evaluated by Wilcoxon signed-rank test and logistic regression analysis. The relationship between GSTK1 and immune infiltration and methylation level was further explored. The expression of GSTK1 and its correlation with immune cell infiltration was verified by Immunohistochemical staining (IHC).</p><p><bold>Results:</bold> GSTK1 was lower in HNSC, BRCA, Lung squamous cell carcinoma, and Thyroid carcinoma than in para-carcinoma. Low GSTK1 expression was associated with worse overall survival in Bladder urothelial carcinoma, Kidney renal papillary cell carcinoma, BRCA, and HNSC. However, only in BRCA and HNSC, GSTK1 expression in tumors was lower than that in normal tissues. Cox regression analyses confirmed that GSKT1 was an independent prognostic factor of overall survival in HNSC patients. The decrease in GSTK1 expression in HNSC was significantly correlated with high T stage and smoker history. IHC showed that the expression level of GSTK1 in HNSC was lower than that in para-carcinoma. In addition, GSEA showed that three pathways related to immune infiltration were positively correlated, while two pathways related to DNA methylation were negatively correlated with expression of GSTK1. Further analysis showed that GSTK1 was moderately positively correlated with the infiltration level of T cells and Cytotoxic cells, which was further confirmed by IHC. The methylation level of GSTK1 was associated with prognosis in patients with HNSC.</p><p><bold>Conclusion:</bold> Low GSTK1 expression may be a potential molecular marker for poor prognosis in HNSC and provide new insight for the development of diagnostic marker or therapeutic target.</p>