Expression Characteristics and Prognostic Study of PPP1R13L in Brain Metastases of Lung Adenocarcinoma.

Background and objective Lung adenocarcinoma is prone to brain metastasis, and the prognosis of patients is extremely poor. The inhibitor of apoptosis-stimulating protein of p53 (iASPP) protein, encoded by the protein phosphatase 1 regulatory subunit 13-like (PPP1R13L) gene, is a key inhibitor of th...

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Published in:Chinese Journal of Lung Cancer Vol. 28; no. 11; pp. 818 - 831
Main Authors: LIU, Luyao, FAN, Peiwen, CHANG, Cheng, WANG, Ruozheng
Format: pictorial research tables/charts Journal Article
Published: Chinese Journal of Lung Cancer Nov2025
Online Access:View this record in EBSCOhost
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        10093419
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      jtl: Chinese Journal of Lung Cancer
      issn: 10093419
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    pubinfo:
      dt: Nov2025
      vid: 28
      iid: 11
      pid: 54191
      pub: Chinese Journal of Lung Cancer
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        191474571
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        191474571
        10.3779/j.issn.1009-3419.2025.106.32
        191474571
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      tig:
        atl: Expression Characteristics and Prognostic Study of PPP1R13L in Brain Metastases of Lung Adenocarcinoma.
      aug:
        au:
          LIU, Luyao
          FAN, Peiwen
          CHANG, Cheng
          WANG, Ruozheng
        affil: Key Laboratory of Xinjiang Oncology, Third Clinical Medical College, Xinjiang Medical University, Urumqi 830011, China
      sug:
        subj:
          Brain Neoplasms
          Neoplasm Metastasis
          Adenocarcinoma of Lung Prognosis
          Disease Attributes
          Gene Expression
          Cell Line, Tumor
          Sequence Analysis
          Human
          Adult
          Middle Age
          Aged
          Aged, 80 and Over
          Male
          Female
          China
          Exploratory Research
          Tissue
          Glioma
          Academic Medical Centers
          Immunohistochemistry
          Adenocarcinoma of Lung Symptoms
          Comparative Studies
          Epithelial Cells
          Phosphorylation
          Signal Transduction
          Cell Differentiation
          Collagen
          Descriptive Statistics
          Confidence Intervals
          Survival Analysis
          RNA
          Cell Viability
          Chi Square Test
          Fisher's Exact Test
          Kaplan-Meier Estimator
          Log-Rank Test
          Univariate Statistics
          Cox Proportional Hazards Model
          Data Analysis Software
          Overall Survival
          Adult: 19-44 years
          Middle Aged: 45-64 years
          Aged: 65+ years
          Aged, 80 & over
          Male
          Female
      ab: Background and objective Lung adenocarcinoma is prone to brain metastasis, and the prognosis of patients is extremely poor. The inhibitor of apoptosis-stimulating protein of p53 (iASPP) protein, encoded by the protein phosphatase 1 regulatory subunit 13-like (PPP1R13L) gene, is a key inhibitor of the p53 pathway and promotes carcinogenesis in various tumors, but its role in brain metastasis of lung adenocarcinoma is unknown. This study aims to analyze the tumor microenvironment characteristics of patients with brain metastasis of lung adenocarcinoma and explore the expression of PPP1R13L in brain metastasis tissues and its clinical significance by single-cell sequencing and clinical sample analysis. Methods Brain tissues from 4 patients with lung adenocarcinoma brain metastasis and 2 patients with oligodendroglioma (ODG) were collected from the Affiliated Tumor Hospital of Xinjiang Medical University from January 2014 to December 2024 for single-cell sequencing. The tumor microenvironment was analyzed by combining single-cell sequencing data from 4 lung adenocarcinoma samples and 4 normal lung tissue samples from public databases. Additionally, clinical data and paraffin sections of 50 patients with lung adenocarcinoma brain metastasis in this hospital were collected, and immunohistochemistry was used to assess iASPP expression and its association with clinicopathologic features and patient outcome. Results Compared with the ODG and lung adenocarcinoma groups, the specific epithelial cells in the lung adenocarcinoma brain metastasis group were mainly enriched in oxidative phosphorylation, apoptosis, hypoxia, and p53 pathways. PPP1R13L, as an upregulated differential gene, was highly expressed in the specific epithelial cell subpopulation of the brain metastasis group; the interaction between PPP1R13L-positive cells and fibroblasts was significant, activating cell-matrix adhesion related pathways, with the key ligand-receptor pair being collagen type I alpha 1 chain-cluster of differentiation 44 (COL1A1-CD44). Statistical evaluation revealed that smoking (HR=2.543, 95%CI: 1.159-5.583, P=0.020) and high expression of iASPP (HR=3.351, 95%CI: 1.310-8.575, P=0.012) were independent predictors of poor prognosis in lung adenocarcinoma patients with brain metastases. Conclusion This study revealed the interaction between epithelial cells and fibroblasts in the microenvironment of lung adenocarcinoma brain metastasis and implicate PPP1R13L as a potential prognostic indicator and actionable target, offering rationale for precision therapy against lung adenocarcinoma brain metastases.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: Chinese
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