Identification of an Anoikis-associated LncRNA Signature to Predict the Clinical Prognosis and Immune Function of Patients with Endometrial Cancer.

IF 3.2 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL
International Journal of Medical Sciences Pub Date : 2025-05-07 eCollection Date: 2025-01-01 DOI:10.7150/ijms.107243
Guanxiao Chen, Ting Zhou, Xiaoyu Shen, Wan Shu, Shuyang Yu, Kejun Dong, Piotr Laudański, Klaudia Gutowska, Shuangshuang Cheng, Hongbo Wang
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引用次数: 0

Abstract

Background: Endometrial cancer is a highly heterogeneous malignancy in women with high mortality, and patients diagnosed with advanced endometrial cancer have a poor prognosis. Anoikis is a form of programmed cell death that is important for cancer development and metastasis. Long non-coding RNAs (lncRNAs) are considered critical regulators of gene expression and key players in cancer biology; however, the effects of anoikis-associated lncRNAs on the prognosis and treatment of patients with endometrial cancer remain unclear. Methods: Using transcriptome sequencing data and clinical information from The Cancer Genome Atlas database, we developed a novel prognostic signature for endometrial cancer based on anoikis-related lncRNAs by combining multivariate regression analysis and least absolute shrinkage and selection operator regression. The signature was validated by receiver operating characteristic (ROC) curve and Kaplan-Meier analyses. After analyzing the relationships between the seven lncRNAs in the signature and tumor progression through gene set enrichment analysis (GSEA), we further explored the differences in immune function and drug sensitivity. Additionally, to investigate the functions of these lncRNAs in the occurrence and development of endometrial cancer, we selected CFAP58-DT to conduct a series of in vitro and in vivo experiments to verify its partial functions. Results: Seven anoikis-associated lncRNAs (CFAP58-DT, AC004585.1, AC103563.9, AL121895.2, AC004596.1, AC010761.4, and AC087564.1) with prognostic value were identified for signature construction. The analysis showed excellent predictive accuracy of the signature (the largest area under the ROC curve = 0.757). GSEA indicated that these lncRNAs may regulate diverse cellular processes, including intercellular interactions, cell proliferation, differentiation, apoptosis, angiogenesis, glucose and fatty acid metabolism, immune responses, and inflammatory regulation. Furthermore, immune analysis revealed a high likelihood of immune evasion and poor immunotherapy efficacy in high-risk patients. However, there were distinct differences in the immune checkpoints and anticancer drug sensitivity between the two patient groups, which may aid in guiding treatment. Finally, our experiments showed that silencing CFAP58-DT significantly affected cell proliferation, promoted apoptosis, and reduced tumor malignancy. Conclusion: Our study highlights the significance of anoikis-associated lncRNAs in endometrial cancer progression and their potential as prognostic markers and therapeutic targets. The signature constructed using these lncRNAs may offer new avenues for endometrial cancer treatment and immunotherapy. The function of CFAP58-DT has been validated in vitro and in vivo, consistent with our previous analysis; however, further research into its upstream and downstream mechanisms is warranted.

鉴定一种anoiki相关LncRNA信号以预测子宫内膜癌患者的临床预后和免疫功能。
背景:子宫内膜癌是一种高度异质性的恶性肿瘤,死亡率高,晚期子宫内膜癌患者预后差。Anoikis是程序性细胞死亡的一种形式,对癌症的发展和转移很重要。长链非编码rna (lncRNAs)被认为是基因表达的关键调控因子和癌症生物学的关键参与者;然而,嗜酸相关lncrna对子宫内膜癌患者预后和治疗的影响尚不清楚。方法:利用来自The Cancer Genome Atlas数据库的转录组测序数据和临床信息,结合多元回归分析、最小绝对收缩和选择算子回归,建立了一种基于anoiks相关lncrna的子宫内膜癌预后新特征。采用受试者工作特征(ROC)曲线和Kaplan-Meier分析对其特征进行验证。通过基因集富集分析(gene set enrichment analysis, GSEA)分析了签名中的7个lncrna与肿瘤进展的关系后,我们进一步探讨了免疫功能和药物敏感性的差异。此外,为了研究这些lncrna在子宫内膜癌发生发展中的功能,我们选择CFAP58-DT进行了一系列体外和体内实验,验证其部分功能。结果:鉴定出7个具有预后价值的抑郁症相关lncrna (CFAP58-DT、AC004585.1、AC103563.9、AL121895.2、AC004596.1、AC010761.4和AC087564.1)用于特征构建。分析结果表明,该特征的预测精度很高(ROC曲线下最大面积= 0.757)。GSEA表明,这些lncrna可能调节多种细胞过程,包括细胞间相互作用、细胞增殖、分化、凋亡、血管生成、葡萄糖和脂肪酸代谢、免疫反应和炎症调节。此外,免疫分析显示高危患者免疫逃避的可能性高,免疫治疗效果差。然而,两组患者在免疫检查点和抗癌药物敏感性方面存在明显差异,这可能有助于指导治疗。最后,我们的实验表明,沉默CFAP58-DT可显著影响细胞增殖,促进细胞凋亡,降低肿瘤恶性程度。结论:我们的研究强调了嗜酸相关lncrna在子宫内膜癌进展中的重要性,以及它们作为预后标志物和治疗靶点的潜力。利用这些lncrna构建的特征可能为子宫内膜癌的治疗和免疫治疗提供新的途径。CFAP58-DT的功能在体外和体内得到验证,与我们之前的分析一致;然而,对其上游和下游机制的进一步研究是必要的。
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
International Journal of Medical Sciences
International Journal of Medical Sciences MEDICINE, GENERAL & INTERNAL-
CiteScore
7.20
自引率
0.00%
发文量
185
审稿时长
2.7 months
期刊介绍: Original research papers, reviews, and short research communications in any medical related area can be submitted to the Journal on the understanding that the work has not been published previously in whole or part and is not under consideration for publication elsewhere. Manuscripts in basic science and clinical medicine are both considered. There is no restriction on the length of research papers and reviews, although authors are encouraged to be concise. Short research communication is limited to be under 2500 words.
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