Liquid–liquid phase separation-related genes associated with prognosis, tumor microenvironment characteristics, and tumor cell features in bladder cancer

Clinical and Translational Oncology Pub Date : 2024-09-13 DOI:10.1007/s12094-024-03719-7

Xiao-Hui Wu, Xu-Yun Huang, Qi You, Jun-Ming Zhu, Qian-Ren-Shun Qiu, Yun-Zhi Lin, Ning Xu, Yong Wei, Xue-Yi Xue, Ye-Hui Chen, Shao-Hao Chen, Qing-Shui Zheng

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Abstract

Objective

This study aimed to explore the Liquid–liquid phase separation (LLPS)-related genes associated with the prognosis of bladder cancer (BCa) and assess the potential application of LLPS-related prognostic signature for predicting prognosis in BCa patients.

Methods

Clinical information and transcriptome data of BCa patients were extracted from the Cancer Genome Atlas-BLCA (TCGA-BLCA) database and the GSE13507 database. Furthermore, 108 BCa patients who received treatment at our institution were subjected to a retrospective analysis. The least absolute shrinkage and selection operator (LASSO) analysis was performed to develop an LLPS-related prognostic signature for BCa. The CCK8, wound healing and Transwell assays were performed.

Results

Based on 62 differentially expressed LLPS-related genes (DELRGs), three DELRGs were screened by LASSO analysis including kallikrein-related peptidase 5 (KLK5), monoacylglycerol O-acyltransferase 2 (MOGAT2) and S100 calcium-binding protein A7 (S100A7). Based on three DELRGs, a novel LLPS-related prognostic signature was constructed for individualized prognosis assessment. Kaplan–Meier curve analyses showed that LLPS-related prognostic signature was significantly correlated with overall survival (OS) of BCa. ROC analyses demonstrated the LLPS-related prognostic signature performed well in predicting the prognosis of BCa patients in the training group (the area under the curve (AUC) = 0.733), which was externally verified in the validation cohort 1 (AUC = 0.794) and validation cohort 2 (AUC = 0.766). Further experiments demonstrated that inhibiting KLK5 could affect the proliferation, migration, and invasion of BCa cells.

Conclusions

In this study, a novel LLPS-related prognostic signature was successfully developed and validated, demonstrating strong performance in predicting the prognosis of BCa patients.

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与膀胱癌预后、肿瘤微环境特征和肿瘤细胞特征相关的液相-液相分离基因

方法从癌症基因组图谱-BLCA（TCGA-BLCA）数据库和GSE13507数据库中提取BCa患者的临床信息和转录组数据。此外，还对在本院接受治疗的108例BCA患者进行了回顾性分析。通过最小绝对缩小和选择算子（LASSO）分析，建立了与LLPS相关的BCa预后特征。结果基于62个差异表达的LLPS相关基因（DELRGs），通过LASSO分析筛选出3个DELRGs，包括allikrein相关肽酶5（KLK5）、单酰甘油O-酰基转移酶2（MOGAT2）和S100钙结合蛋白A7（S100A7）。根据三个 DELRGs，构建了一个新的 LLPS 相关预后特征，用于个体化预后评估。Kaplan-Meier曲线分析表明，LLPS相关预后特征与BCa的总生存期（OS）显著相关。ROC分析表明，LLPS相关预后特征在预测训练组BCa患者的预后方面表现良好（曲线下面积（AUC）=0.733），这在验证组1（AUC=0.794）和验证组2（AUC=0.766）中得到了外部验证。进一步的实验表明，抑制 KLK5 可影响 BCa 细胞的增殖、迁移和侵袭。

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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Clinical and Translational Oncology

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