背景：谷胱甘肽S-转移酶kappa 1（GSTK1）对肉瘤和乳腺癌（BRCA）的发展至关重要。然而，GSTK1在头颈鳞状细胞癌（HNSC）中的临床意义仍不清楚。本研究是对GSTK1在HNSC中作用的首次研究。 方法：所有原始数据均从癌症基因组图谱（TCGA）数据集下载，并通过R Base Package 4.2.0验证。使用TIMER和TCGA数据库探索了GSTK1在各种癌症中的表达。使用Kaplan-Meier绘图仪和Human Protein Atlas数据库以及Cox回归分析来分析GSTK1的预后价值。通过Wilcoxon符号秩检验和logistic回归分析评估了GSTK1与临床特征的关联。进一步探讨了GSTK1与免疫浸润和甲基化水平之间的关系。使用免疫组化染色（IHC）验证了GSTK1的表达及其与免疫细胞浸润的相关性。 结果：HNSC，BRCA，肺鳞状细胞癌和甲状腺癌中的GSTK1低于癌旁组织。低GSTK1表达与膀胱泌尿上皮癌，肾小管细胞癌，BRCA和HNSC患者的全身预后较差有关。然而，只有在BRCA和HNSC中，肿瘤中的GSTK1表达低于正常组织。Cox回归分析证实GSTK1是HNSC患者总体生存的独立预后因子。HNSC中GSTK1表达下降显著与高T期和吸烟史有关。IHC显示，HNSC中GSTK1的表达水平低于癌旁组织。此外，GSEA显示与免疫浸润有关的三条通路与GSTK1的表达呈正相关，而与DNA甲基化有关的两条通路与GSTK1的表达呈负相关。进一步的分析显示，GSTK1与T细胞和细胞毒性细胞的浸润水平有中度正相关，这也得到了IHC的进一步证实。GSTK1的甲基化水平与HNSC患者的预后有关。 结论：低GSTK1表达可能是HNSC患者不良预后的潜在分子标记，并为诊断标记或治疗靶点的开发提供新的见解。 版权所有©2023 Feng, Zhou, Zhao, Su, Chen, Zhao, Ye, Hu, Ou-Yang, Zhong, Yang, Han, Guo和Feng。

Background: 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. Methods: 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 via 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). Results: 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. Conclusion: 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.Copyright © 2023 Feng, Zhou, Zhao, Su, Chen, Zhao, Ye, Hu, Ou-Yang, Zhong, Yang, Han, Guo and Feng.