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

## TL;DR

This study explores the role of PPP1R13L in lung adenocarcinoma brain metastases and identifies it as a potential prognostic marker and treatment target.

## Contribution

The study is the first to investigate the role of PPP1R13L in lung adenocarcinoma brain metastases and its clinical significance.

## Key findings

- PPP1R13L is upregulated in brain metastatic epithelial cells and linked to p53 pathway activation.
- PPP1R13L interacts with fibroblasts via COL1A1-CD44, promoting cell-matrix adhesion.
- Smoking history and high iASPP expression are independent risk factors for poor prognosis.

## Abstract

肺腺癌易发生脑转移，患者预后极差。蛋白磷酸酶1调节亚基13样（protein phosphatase 1 regulatory subunit 13-like, PPP1R13L）基因编码的p53凋亡刺激蛋白家族抑制成员（inhibitor of apoptosis-stimulating protein of p53, iASPP）蛋白是p53通路的关键抑制因子，在多种肿瘤中促癌，但其在肺腺癌脑转移中的作用未知。本研究通过单细胞测序数据整合与临床样本分析，旨在分析肺腺癌脑转移患者的肿瘤微环境特征，并探讨PPP1R13L在脑转移组织中的表达情况及其临床意义。

收集2014年1月至2024年12月新疆医科大学附属肿瘤医院就诊的4例肺腺癌脑转移和2例少突胶质细胞瘤患者的脑组织进行单细胞测序，并结合公共数据库中4例肺腺癌样本和4例正常肺组织样本的单细胞测序数据解析肿瘤微环境；另收集此医院50例肺腺癌脑转移患者的临床资料及石蜡切片，采用免疫组化技术检测iASPP蛋白表达，分析其与临床特征及预后的关系。

相较于胶质瘤和肺腺癌组，肺腺癌脑转移组特异的上皮细胞主要富集于氧化磷酸化、细胞凋亡、缺氧和p53通路；PPP1R13L作为上调差异基因，在脑转移组特异上皮细胞亚群高表达；PPP1R13L阳性细胞与成纤维细胞交互作用显著，激活细胞-基质黏附相关通路，关键配体-受体对为I型胶原蛋白α1链-白细胞分化抗原44（collagen type I alpha 1 chain-cluster of differentiation 44, COL1A1-CD44）。临床数据分析显示，吸烟史（HR=2.543, 95%CI: 1.159-5.583, P=0.020）和iASPP高表达（HR=3.351, 95%CI: 1.310-8.575, P=0.012）为肺腺癌脑转移患者预后的独立危险因素。

本研究阐明了肺腺癌脑转移微环境中上皮细胞与成纤维细胞的相互作用，提示PPP1R13L可作为潜在预后标志物及治疗靶点，为肺腺癌脑转移的精准治疗提供依据。

Baseline characteristics and prognostic factors of 50 patients with LCBM (n=50)