Zhang Chang, Wang Yeli, Yu Yao, Pang Yanchao, Xiao Xiao, Hao Leilei
Department of Anorectal, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai City, Shandong Province, China.
Department of General Pediatric Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai City, Shandong Province, China.
Ann Med. 2025 Dec;57(1):2439539. doi: 10.1080/07853890.2024.2439539. Epub 2024 Dec 10.
Rectal adenocarcinoma (READ) involves the dysregulated expression of alpha 2,8-Sialyltransferase1 (ST8Sia1) although its role during READ's progression is unclear.
The mRNA level of ST8Sia1 was analyzed based on The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Tumor Immune Estimation Resource (TIMER) 2.0. Furthermore, the prognostic and significance of ST8Sia1 in READ was assessed through Kaplan-Meier curve, univariate, multivariate Cox regression, and receiver operating characteristic (ROC) methods. The role of ST8Sia1 in the READ immune microenvironment was explored using ESTIMATE analysis and TIMER databases. Furthermore, the expression of ST8Sia1 in tissues was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting (WB), and immunohistochemistry (IHC). Perforin and Granzyme B secretion by CD8 T cells, as well as tumor cell apoptosis, were detected after co-culturing CD8 T cells with READ tumor cells and ST8Sia1-overexpression (ST8Sia1-OE) tumor cells. Furthermore, we examined the interaction between ST8Sia1 and TGF-β1 in READ cells.
ST8Sia1 exhibited excellent diagnostic capability for READ, with positive correlations to immune response and negative correlations to tumor purity. Increased levels of perforin and Granzyme B from CD8 T cells were observed in vitro, enhancing tumor cell apoptosis. ST8Sia1 interacts with TGF-β1, mediating its inhibitory effects on READ development.
ST8Sia1 is a potential diagnostic biomarker and therapeutic target for READ, enhancing CD8 T cell function and possibly improving patient outcomes through cellular immunotherapy.
直肠腺癌（READ）涉及α2,8-唾液酸转移酶1（ST8Sia1）的表达失调，但其在READ进展过程中的作用尚不清楚。
基于癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和肿瘤免疫评估资源（TIMER）2.0分析ST8Sia1的mRNA水平。此外，通过Kaplan-Meier曲线、单变量、多变量Cox回归和受试者工作特征（ROC）方法评估ST8Sia1在READ中的预后及意义。利用ESTIMATE分析和TIMER数据库探索ST8Sia1在READ免疫微环境中的作用。此外，使用实时定量聚合酶链反应（RT-qPCR）、蛋白质免疫印迹（WB）和免疫组织化学（IHC）分析ST8Sia1在组织中的表达。将CD8 T细胞与READ肿瘤细胞和ST8Sia1过表达（ST8Sia1-OE）肿瘤细胞共培养后，检测CD8 T细胞分泌的穿孔素和颗粒酶B以及肿瘤细胞凋亡情况。此外，我们研究了READ细胞中ST8Sia1与转化生长因子-β1（TGF-β1）之间的相互作用。
ST8Sia1对READ具有出色的诊断能力，与免疫反应呈正相关，与肿瘤纯度呈负相关。体外观察到CD8 T细胞分泌的穿孔素和颗粒酶B水平升高，增强了肿瘤细胞凋亡。ST8Sia1与TGF-β1相互作用，介导其对READ发展的抑制作用。
ST8Sia1是READ的潜在诊断生物标志物和治疗靶点，可增强CD8 T细胞功能，并可能通过细胞免疫疗法改善患者预后。
