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结直肠癌中 PXDC1 表达升高与不良预后及 PD-L1 调控、NK 细胞功能异常相关

英文原题:Elevated PXDC1 expression linked to poor prognosis and abnormalities in PD-L1 regulation and NK cell function in colorectal cancer.

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Elevated PXDC1 expression linked to poor prognosis and abnormalities in PD-L1 regulation and NK cell function in colorectal cancer.

PubMed 2025/10/11(内容时间) Naunyn Schmiedebergs Arch Pharmacol Q2 · IF 4(JCR 2025)

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中文摘要

结直肠癌(CRC)仍是常见恶性肿瘤,治疗结局尚不理想,亟需新的预后和治疗生物标志物。本研究首次探索PXDC1在CRC中的作用,通过转录组、空间转录组和单细胞基因组学分析其差异表达、预后意义及与肿瘤浸润免疫细胞的关系。免疫组化(IHC)证实,CRC组织中的PXDC1表达明显高于正常组织,提示其可能参与CRC进展。CCK8、克隆形成、划痕实验和流式细胞术等功能实验显示,敲低CRC细胞中的PXDC1可抑制增殖和迁移,并诱导凋亡。生物信息学、蛋白质印迹、共培养实验、分子对接及免疫荧光分析进一步发现,PXDC1与PD-L1表达呈正相关。敲低PXDC1可增强NK-92细胞的肿瘤杀伤能力并促进细胞因子释放。

结果表明,PXDC1对CRC进展具有关键作用,其表达升高与预后不良、肿瘤生长、免疫细胞浸润及NK细胞功能受损相关。这提示PXDC1有望成为CRC重要预后生物标志物和有吸引力的治疗靶点,为更精准、靶向的治疗策略提供机会。

展开英文摘要原文

Colorectal cancer (CRC) remains a prevalent malignancy with suboptimal treatment outcomes, underscoring the need for novel prognostic and therapeutic biomarkers. This research is the initial exploration into the role of PXDC1 in CRC, analyzing its differential expression, prognostic significance, and correlation with tumor-infiltrating immune cells through transcriptomics, spatial transcriptomics, and single-cell genomics. Immunohistochemistry (IHC) staining confirmed that PXDC1 expression was notably higher in CRC tissues compared to normal tissues, highlighting its potential role in CRC progression. Functional assays, including CCK8, colony formation, scratch assays, and flow cytometry, showed that PXDC1 knockdown in CRC cells inhibited proliferation, migration, and induced apoptosis.

Additional analyses utilizing bioinformatics, Western blotting, co-culture experiments, molecular docking, and immunofluorescence revealed a positive correlation between PXDC1 and PD-L1 expression. Knockdown of PXDC1 enhanced the tumor-killing capacity of NK-92 cells and promoted increased cytokine release.

These results indicate that PXDC1 is pivotal in CRC progression, where its elevated levels are linked to poor prognosis, tumor growth, immune cell infiltration, and NK cell impairment. This highlights PXDC1's potential as a significant prognostic biomarker and an attractive therapeutic target for CRC, offering opportunities for more precise and targeted treatment approaches.

论文信息

作者
Cheng W、Gao D、Ren J、Liu J
第一作者单位
Chongqing Key Laboratory of New Drug Screening From Traditional Chinese Medicine, Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City & Southwest University, SWU-TAAHC Medicinal Plant Joint R&D Centre, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, People's Republic of China.China
通讯作者单位
School of Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan Province, People's Republic of China. 20130141@kust.edu.cn.China
期刊
Naunyn-Schmiedeberg's archives of pharmacology2026 Feb
原文标识
PubMed 41074964 · DOI 10.1007/s00210-025-04628-4