Liquid-liquid Phase Separation-related Genes Associated with Prognosis, Tumor Microenvironment Characteristics, and Tumor Cell Features in Bladder Cancer

Overview

Journal Clin Transl Oncol

Specialty Oncology

Date 2024 Sep 13

PMID 39269596

Authors

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

Affiliations

Soon will be listed here.

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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