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GXYLT2:透明细胞肾细胞癌中抗PD-1疗效的新兴治疗靶点和预测生物标志物。

GXYLT2: an emerging therapeutic target and predictive biomarker for anti-PD-1 efficacy in clear cell renal cell carcinoma.

作者信息

Guo Tuanjie, Chen Jinyuan, Tan Xiangyin, Tang Heting, Wang Xuan, Chen Siteng, Wang Xiang

机构信息

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Genes Immun. 2025 Feb;26(1):27-35. doi: 10.1038/s41435-024-00312-4. Epub 2024 Dec 5.

Abstract

There are studies reporting that glucoside xylosyltransferase 2 (GXYLT2) has a role in promoting tumor progression, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, RT-qPCR and western blotting were employed to detect the expression level of GXYLT2. RNA interference assays were used to knock down GXYLT2. CCK-8, wound healing assays, clone formation assays, and Transwell assays were utilized to investigate the function of GXYLT2. Bioinformatics analysis was used to explore the tumor microenvironment and potential biological mechanisms. We found that the expression level of GXYLT2 in ccRCC was higher than that in adjacent normal renal tissues. Patients with high GXYLT2 expression have worse clinical outcomes. Knockdown of GXYLT2 inhibits the proliferation, invasion, migration, and clone formation ability of ccRCC cells. Enrichment analysis uncovered that GXYLT2 participates in Wnt, cell cycle, and actin cytoskeleton regulation signaling pathways. After receiving anti-PD-1 therapy, patients with high GXYLT2 expression had longer progression-free survival compared with those with low GXYLT2 expression. In conclusion, GXYLT2 is a novel potential therapeutic target for ccRCC. Meanwhile, GXYLT2 can be used as a novel marker for predicting immunotherapeutic response.

摘要

有研究报道葡萄糖苷木糖基转移酶2(GXYLT2)在促进肿瘤进展中起作用,但其在透明细胞肾细胞癌(ccRCC)中的作用仍不清楚。在本研究中,采用RT-qPCR和蛋白质免疫印迹法检测GXYLT2的表达水平。利用RNA干扰实验敲低GXYLT2。采用CCK-8、伤口愈合实验、克隆形成实验和Transwell实验研究GXYLT2的功能。运用生物信息学分析探索肿瘤微环境和潜在生物学机制。我们发现,ccRCC中GXYLT2的表达水平高于相邻正常肾组织。GXYLT2高表达的患者临床预后较差。敲低GXYLT2可抑制ccRCC细胞的增殖、侵袭、迁移和克隆形成能力。富集分析发现,GXYLT2参与Wnt、细胞周期和肌动蛋白细胞骨架调节信号通路。接受抗PD-1治疗后,GXYLT2高表达的患者无进展生存期比GXYLT2低表达的患者更长。总之,GXYLT2是ccRCC一种新的潜在治疗靶点。同时,GXYLT2可作为预测免疫治疗反应的新标志物。

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