Darzi Mohammad, Shokrollahi-Barough Mahdieh, Nazeri Elahe, Majidzadeh-A Keivan, Esmaeili Rezvan
Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
Medical Informatics Research Group, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
Mol Biol Res Commun. 2025;14(3):203-218. doi: 10.22099/mbrc.2025.51329.2050.
Dedifferentiated Liposarcoma (DDLPS) is one of the common subtypes of liposarcoma that is considered a highly malignant category. This study aims to investigate DDLPS through a system biology approach. The gene expression profiles and clinical traits of the DDLPS were acquired from The Cancer Genome Atlas (TCGA). The identification of co-expressed modules was conducted using the weighted gene co-expression network analysis. The immune cell-related gene function was studied by a web-based tool, TIMER, and, the survival analysis was performed at both the module and single-gene levels through Cox Regression analysis. Gene enrichment analysis was also conducted using the DAVID tool. One of the nine co-expressed DDLPS modules was significantly correlated with leukocyte fraction, hyper/hypo methylation, tumor purity, and chromosome instability (CIN). Based on the biological processes used to classify genes, the hub genes in a particular module play important roles in DNA repair, microtubule organizing clusters, mitotic checkpoint dysregulation, and cell proliferation signaling pathways. After screening the genes based on intra-module connectivity, module membership, and gene significance was selected as one of the important hub genes. showed poor prognosis to the overall survival (OS) analysis (HR=1.6, 95% CI=1.1-2.4, p=0.02). No co-expressed modules had relationship with OS. Through DDLPS traits, CIN and hyper/hypo methylation had significant negative relationship with OS. Our achievement confirmed the inverse association between tumor purity for DDLPS gene profiles and leukocyte fraction and negative leukocyte fraction (LF) gene significance in some genes was justified according to the sub-population analyses of immune cells in TIMER.
去分化脂肪肉瘤（DDLPS）是脂肪肉瘤的常见亚型之一，被认为是一种高度恶性的类型。本研究旨在通过系统生物学方法研究DDLPS。DDLPS的基因表达谱和临床特征来自癌症基因组图谱（TCGA）。使用加权基因共表达网络分析进行共表达模块的鉴定。通过基于网络的工具TIMER研究免疫细胞相关基因功能，并通过Cox回归分析在模块和单基因水平上进行生存分析。还使用DAVID工具进行基因富集分析。九个共表达的DDLPS模块之一与白细胞分数、高/低甲基化、肿瘤纯度和染色体不稳定性（CIN）显著相关。基于用于分类基因的生物学过程，特定模块中的枢纽基因在DNA修复、微管组织簇、有丝分裂检查点失调和细胞增殖信号通路中起重要作用。根据模块内连通性、模块成员关系和基因显著性筛选基因后，选择 作为重要的枢纽基因之一。对总生存期（OS）分析显示预后不良（HR=1.6，95%CI=1.1-2.4，p=0.02）。没有共表达模块与OS相关。通过DDLPS特征分析，CIN和高/低甲基化与OS呈显著负相关。我们的研究结果证实了DDLPS基因谱的肿瘤纯度与白细胞分数之间的负相关，并且根据TIMER中免疫细胞的亚群分析，某些基因中白细胞分数（LF）基因显著性为负是合理的。
