Department of Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Department of Geriatrics, Affiliated Provincial Hospital of Anhui Medical University, Hefei, 230001, China.
Reprod Sci. 2024 Feb;31(2):532-549. doi: 10.1007/s43032-023-01363-0. Epub 2023 Oct 5.
Poor neoplastic differentiation contributes to the rapid progression of uterine corpus endometrial carcinoma (UCEC). Thus, it is essential to identify candidate genes, clarifying the carcinogenesis and progression of UCEC.
We screened genes that affect differentiation and prognosis in UCEC. Least absolute selection and shrinkage operator (LASSO) regression, univariate Cox, and multivariate Cox proportional risk regression analyses were performed to screen out γ-glutamyl hydrolase (GGH) as the candidate gene. The clinical value of GGH on prognosis was evaluated. The relationship between GGH and immune infiltration was assessed by CIBERSORT, EPIC, ssGSEA, unsupervised clustering and immunohistochemistry (IHC). Additionally, we investigated the effect of GGH knockdown in vitro.
Among the GGH, CDKN2A, and SIX1 genes, the impact of GGH was predominant on immune infiltration in UCEC. A nomogram containing GGH and other clinical features showed good predictive performance via curve analysis (DCA). In the functional analysis, GGH affected differentiation, tumour proliferation, and immune regulation. The immunosuppressive components were enriched in the GGH-high group, with poor immunotherapy efficacy. The study suggests that GGH may influence the progression of UCEC by regulating the glycolytic process.
GGH is closely associated with various immune cell infiltrations. Our study demonstrates the prognostic role of GGH in carcinogenesis in UCEC.
不良的肿瘤分化导致了子宫体子宫内膜癌（UCEC）的快速进展。因此，识别候选基因对于阐明 UCEC 的发生和进展至关重要。
我们筛选了影响 UCEC 分化和预后的基因。采用最小绝对选择和收缩算子（LASSO）回归、单因素 Cox 分析和多因素 Cox 比例风险回归分析筛选出γ-谷氨酰水解酶（GGH）作为候选基因。评估 GGH 对预后的临床价值。通过 CIBERSORT、EPIC、ssGSEA、无监督聚类和免疫组织化学（IHC）评估 GGH 与免疫浸润的关系。此外，我们还研究了 GGH 体外敲低的效果。
在 GGH、CDKN2A 和 SIX1 基因中，GGH 对 UCEC 中的免疫浸润影响最为显著。包含 GGH 和其他临床特征的列线图通过曲线分析（DCA）显示出良好的预测性能。在功能分析中，GGH 影响了分化、肿瘤增殖和免疫调节。在 GGH 高表达组中富集了免疫抑制成分，免疫治疗效果较差。研究表明，GGH 可能通过调节糖酵解过程影响 UCEC 的进展。
GGH 与各种免疫细胞浸润密切相关。本研究表明 GGH 在 UCEC 发生过程中具有预后作用。
