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

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

  • Naunyn Schmiedebergs Arch Pharmacol. 2025 Oct 11. doi: 10.1007/s00210-025-04628-4.
Wei Cheng 1,  Di Gao 2,  Junyu Ren 3,  Jiaxin Liu 4
Affiliations

Affiliations

  • 1 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.
  • 2 College of Foreign Languages, Qingdao City University, Qingdao, 266106, Shandong Province, People's Republic of China.
  • 3 Department of Surgical Oncology, The First Affiliated Hospital of Kunming Medical University, 295 Xichang RoadYunnan Province, Kunming, 650032, People's Republic of China. renjunyu@kmmu.edu.cn.
  • 4 School of Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan Province, People's Republic of China. 20130141@kust.edu.cn.
PMID: 41074964 DOI: 10.1007/s00210-025-04628-4
Abstract

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.

Keywords

Colorectal cancer (CRC); PXDC1; Prognostic biomarkers; Single-cell genomics; Tumor-infiltrating immune cells.

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