Construction of a lipid metabolism-based prognostic gene signature in cervical squamous cell carcinoma and validation of LIPG's oncogenic role.

IF 6 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2025-10-14 DOI:10.1186/s12935-025-03991-9

Gaigai Bai, Fanghua Chen, Junjun Qiu, Keqin Hua

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引用次数: 0

Abstract

Background: Cervical cancer, in which cervical squamous cell carcinoma (CSCC) accounts for 60-70% of cases, has a poor prognosis and poses a significant health threat to global patients. Lipid metabolism reprogramming is a key driver of tumor progression and tumor microenvironment (TME) regulation, making it a promising target for improving the efficacy of immunotherapy. This study aimed to construct a lipid metabolism prognostic signature (LMPS) in CSCC and identify key genes involved in tumor progression.

Methods: Through RNA-sequencing and clinical data from TCGA and GTEx databases, we identified differentially expressed lipid metabolism-related genes (DLMGs) and constructed the LMPS using machine learning algorithms. Next, the value of the LMPS was validated using the HTMCP database and the GEO database. Furthermore, the relationship between the LMPS and the TME was analyzed, including immune cell infiltration, immune checkpoint gene expression, and drug sensitivity. The key gene lipase G (LIPG) was identified through machine learning methods and validated through cellular and molecular biology experiments.

Results: A total of 60 DLMGs were identified, with 9 DLMGs showing prognostic value. The LMPS was constructed using 6 genes (ACOT4, PLA2G2D, GAL3ST1, ALOX12B, PLA2G3, and LIPG), which effectively predicted patients' survival (AUC: 0.76, 0.75, 0.68 at 1, 3, 5 years, respectively). High LMPS was correlated with an immune-suppressive TME, reduced immune cell infiltration, lower human leukocyte antigen (HLA) and immune checkpoint gene expression, and higher IC50 values for common chemotherapy drugs. LIPG was identified as a key gene, showing higher expression in advanced cancer stages. As revealed by functional experiments, LIPG promoted lipid accumulation and phosphatidylcholine (PC) hydrolysis in CSCC cells. Additionally, LIPG facilitated tumor progression through activation of the MAPK-p38 signaling pathway.

Conclusions: The LMPS was a valuable prognostic tool and was correlated with the TME and drug sensitivity. LIPG was a key regulator of lipid metabolism and facilitated CSCC development by hydrolyzing PC into lysophosphatidylcholine (LPC) and activating the MAPK-p38 signaling pathway. These findings may highlight the potential of targeting lipid metabolism for therapeutic intervention in CSCC.

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基于脂质代谢的宫颈鳞状细胞癌预后基因标记的构建和LIPG致癌作用的验证。

背景：宫颈癌预后差，对全球患者健康构成重大威胁，其中宫颈鳞状细胞癌（CSCC）占60-70%。脂质代谢重编程是肿瘤进展和肿瘤微环境（tumor microenvironment， TME）调控的关键驱动因素，是提高免疫治疗疗效的一个有希望的靶点。本研究旨在构建CSCC的脂质代谢预后标记（LMPS），并确定参与肿瘤进展的关键基因。方法：通过rna测序和TCGA和GTEx数据库的临床数据，鉴定脂质代谢相关差异表达基因（dlmg），并利用机器学习算法构建LMPS。接下来，使用html数据库和GEO数据库验证LMPS的值。进一步分析LMPS与TME的关系，包括免疫细胞浸润、免疫检查点基因表达和药物敏感性。通过机器学习方法确定关键基因脂肪酶G (LIPG)，并通过细胞和分子生物学实验进行验证。结果：共发现60个dlmg，其中9个dlmg具有预后价值。LMPS使用6个基因（ACOT4、PLA2G2D、GAL3ST1、ALOX12B、PLA2G3和LIPG）构建，有效预测患者的生存（AUC分别为0.76、0.75、0.68，分别为1年、3年和5年）。高LMPS与免疫抑制TME、免疫细胞浸润减少、人白细胞抗原（HLA）和免疫检查点基因表达降低以及常见化疗药物的IC50值升高相关。LIPG被认为是一个关键基因，在癌症晚期表现出更高的表达。功能实验显示，LIPG促进CSCC细胞脂质积累和磷脂酰胆碱（PC）水解。此外，LIPG通过激活MAPK-p38信号通路促进肿瘤进展。结论：LMPS是一种有价值的预后工具，与TME和药物敏感性相关。LIPG是脂质代谢的关键调节因子，通过将PC水解成溶血磷脂酰胆碱（LPC）并激活MAPK-p38信号通路，促进CSCC的发展。这些发现可能突出了针对脂质代谢进行CSCC治疗干预的潜力。

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

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.