揭示寡糖转移酶STT3B在结直肠癌组织中的作用:临床意义和驱动三级淋巴结构形成的分子机制

IF 2.5 4区 医学 Q3 IMMUNOLOGY
Caixia Zhang , Bin Wang , Xiaofeng Bian , Youcai Zhao , Xiaobing Yang , Wei Zhao
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引用次数: 0

摘要

三级淋巴结构(TLS)在抗肿瘤反应中的作用已引起越来越多的关注;然而,各种TLS亚型的临床意义和调控机制仍然知之甚少。本研究探讨了低聚糖转移酶亚基STT3B在调节结直肠癌(CRC)组织中TLS形成和B细胞活性中的功能。利用空间形态学分析准确识别STT3B在TLS中的表达定位。通过结合临床样本和生物信息学分析,我们检测了STT3B在结直肠癌微环境中的表达水平和分布模式,并评估了其临床意义。转录组测序结合体外验证,用于评估STT3B敲低对B细胞功能的影响。研究结果提示,TLS中STT3B表达密度高的结直肠癌患者预后较好。多色荧光分析进一步证实,STT3B+CD19+ B细胞的密度与结直肠癌患者的病理特征和淋巴结转移状态相关,密度越高,无病生存期越长。转录组测序进一步证明STT3B敲低主要影响B细胞代谢功能。体外实验证实STT3B下调可抑制B细胞的代谢和增殖。这些研究结果表明,STT3B在增强B细胞代谢和促进成熟TLS的发展中起着至关重要的作用,这与CRC患者预后的改善有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unveiling the Role of Oligosaccharyltransferase STT3B in Colorectal Cancer Tissues: Clinical significance and Molecular Mechanisms Driving the Formation of Tertiary Lymphoid Structures
The role of tertiary lymphatic structures (TLS) in anti-tumor response has garnered increasing attention; however, the clinical implications and regulatory mechanisms of various TLS subtypes remain poorly understood. This study investigates the function of the oligosaccharyltransferase subunit STT3B in modulating TLS formation and B cell activity within colorectal cancer (CRC) tissues. Spatial morphology analysis was employed to accurately identify the localization of STT3B expression within TLS. By integrating clinical samples with bioinformatics analyses, we examined the expression levels and distribution patterns of STT3B in the CRC microenvironment and assessed its clinical significance. Transcriptome sequencing, combined with in vitro validation, was utilized to evaluate the effects of STT3B knockdown on B cell functionality. The findings indicated that CRC patients with a high density of STT3B expression in the TLS had a better prognosis. Multicolor fluorescence analysis further demonstrated that the density of STT3B+CD19+ B cells correlated with pathological characteristics and lymph node metastasis status in CRC patients, with higher densities predicting longer disease-free survival. Transcriptome sequencing further demonstrated that STT3B knockdown predominantly impacts B cell metabolic functions. In vitro experiments confirmed that the downregulation of STT3B inhibits the metabolism and proliferation of B cells. These findings suggest that STT3B plays a crucial role in enhancing B cell metabolism and facilitating the development of mature TLS, which is associated with improved prognostic outcomes in patients with CRC.
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来源期刊
Immunobiology
Immunobiology 医学-免疫学
CiteScore
5.00
自引率
3.60%
发文量
108
审稿时长
55 days
期刊介绍: Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.
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