Integration of Machine Learning and Experimental Validation to Identify Anoikis-Related Prognostic Signature for Predicting the Breast Cancer Tumor Microenvironment and Treatment Response.

Journal: Genes
PMID: 39596658

Abstract

Anoikis-related genes (ANRGs) are crucial in the invasion and metastasis of breast cancer (BC). The underlying role of ANRGs in the prognosis of breast cancer patients warrants further study. The anoikis-related prognostic signature (ANRS) was generated using a variety of machine learning methods, and the correlation between the ANRS and the tumor microenvironment (TME), drug sensitivity, and immunotherapy was investigated. Moreover, single-cell analysis and spatial transcriptome studies were conducted to investigate the expression of prognostic ANRGs across various cell types. Finally, the expression of ANRGs was verified by RT-PCR and Western blot analysis (WB), and the expression level of PLK1 in the blood was measured by the enzyme-linked immunosorbent assay (ELISA). The ANRS, consisting of five ANRGs, was established. BC patients within the high-ANRS group exhibited poorer prognoses, characterized by elevated levels of immune suppression and stromal scores. The low-ANRS group had a better response to chemotherapy and immunotherapy. Single-cell analysis and spatial transcriptomics revealed variations in ANRGs across cells. The results of RT-PCR and WB were consistent with the differential expression analyses from databases. NU.1025 and imatinib were identified as potential inhibitors for SPIB and PLK1, respectively. Additionally, findings from ELISA demonstrated increased expression levels of PLK1 in the blood of BC patients. The ANRS can act as an independent prognostic indicator for BC patients, providing significant guidance for the implementation of chemotherapy and immunotherapy in these patients. Additionally, PLK1 has emerged as a potential blood-based diagnostic marker for breast cancer patients.

Authors

  • Longpeng Li
    Department of Anesthesiology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
  • Longhui Li
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Vision Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, Guangdong, China.
  • Yaxin Wang
    Institute of Physical Education and Sport, Shanxi University, Taiyuan, China.
  • Baoai Wu
    Institute of Physical Education and Sport, Shanxi University, Taiyuan 030006, China.
  • Yue Guan
    Institute for Medical Imaging Technology, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Yinghua Chen
    National Clinical Research Centre of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
  • Jinfeng Zhao
    Institute of Physical Education and Sport, Shanxi University, Taiyuan, China.

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