Du Yali, Lan Ting, Liu Mengyuan, Wu Weiyan, Ma Jinqi
Department of Obstetrics and Gynecology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China.
Transl Cancer Res. 2025 Aug 31;14(8):5045-5058. doi: 10.21037/tcr-2025-1405. Epub 2025 Aug 28.
Uterine sarcoma constitutes approximately 3-7% of all uterine cancers, with adenosarcoma and leiomyosarcoma being the major subtypes. This neoplasm is characterized by poor clinical outcomes, with frequent recurrence and metastasis, underscoring the urgent need for early detection strategies. Cyclin-dependent kinase regulatory subunit 2 () is markedly overexpressed in uterine sarcoma. Preliminary data suggest that overexpression correlates with advanced tumor staging, yet its mechanistic link to immune evasion via natural killer T (NKT)-cell regulation remains unexplored. This study aimed to explore how regulates the immune response in uterine sarcoma.
Through the integration of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, a systematic analysis was conducted on the correlation between expression levels, tumor prognostic staging, and immune cell infiltration. Stable -knockdown cell lines were constructed, and the expression changes of were detected via quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot techniques. Through colony formation assays, TUNEL staining, invasion and migration assays, and Western blot analysis, the mechanism related to the regulatory effect of on the malignant progression of uterine sarcoma cells was clarified in depth. Additionally, the specific mechanism by which regulates NKT cell activity was verified at the tissue level via multiplex immunofluorescence.
In uterine sarcoma, expression was found to be significantly upregulated and closely associated with poor prognosis, advanced tumor stage, and a distinct negative correlation with NKT cell activity. experiments indicated that knockdown of significantly inhibited the proliferation, migration, and invasion of sarcoma cells and promoted apoptosis. Mechanistically, activated the signaling, reduced major histocompatibility complex (MHC) class I chain-related protein A () expression, and inhibited NKT cell activity, resulting in immune escape, which was effectively mitigated by inhibitors.
The findings suggest that can serve as a valuable biomarker and an effective target for the prevention and screening of uterine sarcoma and can modify the antitumor immune response in uterine sarcoma.
子宫肉瘤约占所有子宫癌的3 - 7%，腺肉瘤和平滑肌肉瘤是主要亚型。这种肿瘤的临床预后较差，复发和转移频繁，凸显了早期检测策略的迫切需求。细胞周期蛋白依赖性激酶调节亚基2（）在子宫肉瘤中显著过表达。初步数据表明，过表达与肿瘤晚期分期相关，但其通过自然杀伤T（NKT）细胞调节与免疫逃逸的机制联系仍未被探索。本研究旨在探讨如何调节子宫肉瘤中的免疫反应。
通过整合癌症基因组图谱（TCGA）和基因表达综合数据库（GEO），对表达水平、肿瘤预后分期和免疫细胞浸润之间的相关性进行了系统分析。构建了稳定的敲低细胞系，并通过定量逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹技术检测的表达变化。通过集落形成试验、TUNEL染色、侵袭和迁移试验以及蛋白质免疫印迹分析，深入阐明了对子宫肉瘤细胞恶性进展的调节作用相关机制。此外，通过多重免疫荧光在组织水平验证了调节NKT细胞活性的具体机制。
在子宫肉瘤中，发现表达显著上调，与不良预后、肿瘤晚期密切相关，与NKT细胞活性呈明显负相关。实验表明，敲低显著抑制肉瘤细胞的增殖、迁移和侵袭，并促进细胞凋亡。机制上，激活信号通路，降低主要组织相容性复合体（MHC）I类链相关蛋白A（）的表达，并抑制NKT细胞活性，导致免疫逃逸，而抑制剂可有效减轻这种情况。
研究结果表明，可作为子宫肉瘤预防和筛查的有价值生物标志物和有效靶点，并可改变子宫肉瘤中的抗肿瘤免疫反应。
