Liquid-Liquid Phase Separation in the Prognosis of Lung Adenocarcinoma: An Integrated Analysis.

IF 2.3 4区医学 Q3 ONCOLOGY

Current cancer drug targets Pub Date : 2024-11-06 DOI:10.2174/0115680096345676241001081051

Qilong Wang, Nannan Sun, Jianhao Li, Fengxiang Huang, Zhao Zhang

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引用次数: 0

Abstract

Background: Lung adenocarcinoma (LUAD) is a highly lethal malignancy. Liquid-Liquid Phase Separation (LLPS) plays a crucial role in targeted therapies for lung cancer and in the progression of lung squamous cell carcinoma. However, the role of LLPS in the progression and prognosis of LUAD remains insufficiently explored.

Methods: This study employed a multi-step approach to identify LLPS prognosis-related genes in LUAD. First, differential analysis, univariate Cox regression analysis, Random Survival For-est (RSF) method, and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regres-sion analysis were utilized to identify five LLPS prognosis-related genes. Subsequently, LASSO Cox regression was performed to establish a prognostic score termed the LLPS-related progno-sis score (LPRS). Comprehensive analyses were then conducted based on the LPRS, including survival analysis, clinical feature analysis, functional enrichment analysis, and tumor microenvi-ronment assessment. The LPRS was integrated with additional clinicopathological factors to de-velop a prognostic nomogram for LUAD patients. Immunohistochemical validation was per-formed on clinical tissue samples to further validate the findings. Finally, the relationship be-tween KRT6A, one of the identified genes, and epidermal growth factor receptor (EGFR) muta-tions was investigated.

Results: The LPRS was established using five LLPS-related genes: IGF2BP1, KRT6A, LDHA, PKP2, and PLK1. Higher LPRS was closely associated with poor survival outcomes, gender, progression-free survival (PFS), and advanced TNM stage. Furthermore, LPRS emerged as an independent prognostic factor for LUAD. A nomogram integrating LPRS, TNM stage, and age demonstrated remarkable predictive accuracy for prognosis among patients with LUAD. LLPS likely influences LUAD prognosis through the activity of IGF2BP1, KRT6A, LDHA, PKP2, and PLK1. KRT6A exhibits significant upregulation in LUAD, particularly in patients with EGFR mutations.

Conclusion: This study introduces a novel LPRS model that demonstrates high accuracy in pre-dicting the clinical prognosis of LUAD. Moreover, the findings suggest that KRT6A may play a critical role in the LLPS-mediated malignant progression of LUAD.

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液-液相分离在肺腺癌预后中的应用：综合分析

背景：肺腺癌（LUAD）是一种高度致命的恶性肿瘤：肺腺癌（LUAD）是一种致死率极高的恶性肿瘤。液-液相分离（LLPS）在肺癌的靶向治疗和肺鳞癌的进展中发挥着至关重要的作用。然而，LLPS在LUAD的进展和预后中的作用仍未得到充分探索：本研究采用多步骤方法鉴定 LLPS 在 LUAD 中与预后相关的基因。首先，利用差分分析、单变量 Cox 回归分析、随机存活率法（RSF）和最小绝对收缩和选择操作器（LASSO）Cox 回归分析确定了 5 个 LLPS 预后相关基因。随后，通过 LASSO Cox 回归建立了一个预后评分，称为 LLPS 相关预后评分（LPRS）。然后根据 LPRS 进行综合分析，包括生存分析、临床特征分析、功能富集分析和肿瘤微环境评估。LPRS 与其他临床病理因素相结合，为 LUAD 患者制定了预后提名图。为了进一步验证研究结果，还对临床组织样本进行了免疫组化验证。最后，研究了已确定基因之一 KRT6A 与表皮生长因子受体（EGFR）突变之间的关系：结果：利用五个与 LLPS 相关的基因建立了 LPRS：结果：利用五个 LLPS 相关基因建立了 LPRS，这五个基因是：IGF2BP1、KRT6A、LDHA、PKP2 和 PLK1。较高的LPRS与不良生存结果、性别、无进展生存期（PFS）和晚期TNM分期密切相关。此外，LPRS还是LUAD的一个独立预后因素。一个整合了 LPRS、TNM 分期和年龄的提名图显示了对 LUAD 患者预后的显著预测准确性。LLPS可能通过IGF2BP1、KRT6A、LDHA、PKP2和PLK1的活性影响LUAD的预后。KRT6A在LUAD中表现出明显的上调，尤其是在表皮生长因子受体突变的患者中：本研究介绍了一种新型 LPRS 模型，该模型在预测 LUAD 的临床预后方面具有很高的准确性。此外，研究结果表明，KRT6A可能在LLPS介导的LUAD恶性进展中起着关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current cancer drug targets 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

105

审稿时长

1 months

期刊介绍： Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.