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铁死亡相关基因的综合分析表明,ABHD12是一种新型的预后生物标志物,并促进肝细胞癌的肿瘤发生。

Integrative analysis of ferroptosis-related genes reveals that ABHD12 is a novel prognostic biomarker and facilitates hepatocellular carcinoma tumorigenesis.

作者信息

Mao Tiantao, Zhang Maosong, Peng Zupei, Tang Min, Li Tianyu, Liang Chengshu

机构信息

Department of Oncology, Wuxi County People's Hospital, No. 100 Wantong Road, Baiyang Street, Chongqing, 405899, China.

出版信息

Discov Oncol. 2024 Aug 2;15(1):330. doi: 10.1007/s12672-024-01211-w.

Abstract

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, making the prognostic prediction challenging. Ferroptosis, an iron-dependent form of cell death, is a key regulator in the initiation, progression, and metastasis of HCC. However, the expression and function of ferroptosis-related genes (FRGs) in HCC remained largely unclear. In this study, we analyzed TCGA datasets and identified 58 survival-related deferentially expressed FRGs (DE-FRGs). Then, based on the results of LASSO analysis, we developed a novel prognostic model based on 12 survival-related DE-FRGs. Survival assays indicated a strong prognostic ability of this new model in predicting clinical prognosis of HCC patients. In addition, we conducted an exploration of molecular subtypes related to HCC and delved into the associated immune characteristics and gene expression patterns. Among the 12 survival-related DE-FRGs, our attention focused on ABHD12 (abhydrolase domain containing 12) which was highly expressed in HCC and associated with advanced clinical stages. Multivariate assays confirmed that ABHD12 was a significant prognostic factor for HCC patients. Immune analysis revealed that ABHD12 may play an important role in tumor microenvironment. Finally, we performed RT-PCR and confirmed that ABHD12 was highly expressed in HCC cells. Functional experiments revealed that ABHD12 knockdown may suppress the proliferation and migration of HCC cells. These findings emphasized the significance of ABHD12 as a potential prognostic marker for HCC and its crucial role in the field of tumor biology. Additionally, the study introduces a novel survival model that holds promise for enhancing prognostic predictions in HCC patients. Overall, this research provided valuable insights for a deeper comprehension of the complexity of HCC and the development of personalized treatment strategies.

摘要

肝细胞癌(HCC)是一种高度异质性疾病,使得预后预测具有挑战性。铁死亡是一种铁依赖性细胞死亡形式,是HCC发生、发展和转移的关键调节因子。然而,HCC中铁死亡相关基因(FRGs)的表达和功能仍不清楚。在本研究中,我们分析了TCGA数据集,鉴定出58个与生存相关的差异表达FRGs(DE-FRGs)。然后,基于LASSO分析结果,我们构建了一个基于12个与生存相关的DE-FRGs的新型预后模型。生存分析表明,该新模型在预测HCC患者临床预后方面具有很强的预后能力。此外,我们对与HCC相关的分子亚型进行了探索,并深入研究了相关的免疫特征和基因表达模式。在12个与生存相关的DE-FRGs中,我们重点关注了ABHD12(含水解酶结构域12),其在HCC中高表达并与晚期临床阶段相关。多变量分析证实,ABHD12是HCC患者的一个重要预后因素。免疫分析显示,ABHD12可能在肿瘤微环境中发挥重要作用。最后,我们进行了RT-PCR并证实ABHD12在HCC细胞中高表达。功能实验表明,敲低ABHD12可能抑制HCC细胞的增殖和迁移。这些发现强调了ABHD12作为HCC潜在预后标志物的重要性及其在肿瘤生物学领域的关键作用。此外,该研究引入了一种新型生存模型,有望提高HCC患者的预后预测。总体而言,本研究为深入理解HCC的复杂性和制定个性化治疗策略提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9edb/11297018/70da2dbc7a04/12672_2024_1211_Fig1_HTML.jpg

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