γ-谷氨酰環轉移酶做為人類乳癌新穎臨床病理學的生物標記以及其腫瘤免疫微環境角色

γ-glutamylcyclotransferase as a Novel Clinicopathological Biomarker and Its Implication in Tumor Immune Microenvironment of Human Breast Cancer

乳癌是最常見的惡性腫瘤，也是全世界女性患者癌症相關死亡率的主要原因。癌細胞與其腫瘤免疫微環境之間的關係對於腫瘤的生長、擴散和治療反應至關重要。γ-谷氨酰環轉移酶（GGCT）在穀胱甘肽代謝循環和腫瘤生長中起核心作用。然而，GGCT在乳癌中GGCT的臨床病理學和腫瘤免疫微環境的意義尚待闡明。本研究使用DriverDB的多組學分析用於篩選GGCT在乳癌隊列中的意義。分別使用TNMplot入口網站和KM Plotter確定GGCT基因表達的診斷和預後意義分析。通過使用臨床蛋白質組腫瘤分析聯盟存儲庫和免疫組織化學數據存儲庫進行蛋白質表達比較。通過TISIDB和TIMER評估GGCT與人乳癌腫瘤中免疫細胞含量的相關性。訓練集和驗證集包含在上述分析中。結果顯示在多麥克風總結小組中注意到GGCT表達水平的上調及其作為乳癌患者生存風險因素的作用。與正常組織相比，在乳癌中注意到遺傳和蛋白質水平的GGCT表達增加。高GGCT顯示與不利的總生存期（OS）和無復發生存期（RFS）相關。此外，GGCT表達水平與自然殺手（NK）細胞、細胞毒性T細胞、記憶B細胞和樹突狀細胞（DC）呈負相關。高GGCT水平被確定為乳癌診斷和預後的遺傳和臨床病理學生物標誌物。高GGCT與免疫抑制腫瘤免疫微環境的關聯可能為開發新的治療方法提供了可能的途徑。

Breast cancer (BRCA) is the most prevalent malignancy and a leading cause cancer-related mortality among female patients globally. The interplay between cancer cells and their Tumor immune microenvironment (TIME) is crucial for tumor growth, spread, and therapeutic response.γ-glutamylcyclotransferase (GGCT) plays a pivotal role in the glutathione metabolism cycle and tumor growth. However, the implication of GGCT in clinicopathology and tumor immune microenvironment (TIME) of GGCT in BRCA has yet to be clarified. In this study, multi-omics analysis using DriverDB was used to screen the significance of GGCT in BRCA cohort. Analysis on the diagnostic and prognostic significance of GGCT gene expression was determined using TNMplot web portal and KM Plotter, respectively. The protein expression comparison was conducted utilizing Clinical Proteomic Tumor Analysis Consortium (CPTAC) repository and immunohistochemical (IHC) data repository. The correlation of GGCT with immune cell content in human BRCA tumor was evaluated by TISIDB and TIMER. Both training and validation sets were included in the aforementioned analysis. Upregulation of GGCT expression levels and its role as a risk factor in BRCA patients’survival were noted in multi-mics summary panel. Increased GGCT expression at the genetic and protein level was observed in BRCA compared to normal tissue. High GGCT showed an association with unfavorable overall survival (OS) and relapse-free survival (RFS). Furthermore, GGCT expression levels correlated negatively with natural killer (NK) cell, cytotoxic T cell, memory B cell and dendritic cell (DC). In summary, high GGCT levels was identified as a genetic and clinicopathological biomarker in BRCA diagnosis and prognosis. The association of high GGCT with immunosuppressive TIME may render a possible path to the development of new therapeutic approaches.