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二硫键相关长非编码 RNA 特征可预测肾透明细胞癌的预后和免疫反应。

Disulfidptosis-associated LncRNA signature predicts prognosis and immune response in kidney renal clear cell carcinoma.

机构信息

Central Laboratory Department, Binhai County People's Hospital, Clinical Medical College of Yangzhou University, Yancheng, China.

Nephrology Department, Binhai County People's Hospital, Yancheng, China.

出版信息

Biol Direct. 2024 Aug 22;19(1):71. doi: 10.1186/s13062-024-00517-7.

Abstract

BACKGROUND

Kidney renal clear cell carcinoma (KIRC) represents a significant proportion of renal cell carcinomas and is characterized by high aggressiveness and poor prognosis despite advancements in immunotherapy. Disulfidptosis, a novel cell death pathway, has emerged as a critical mechanism in various cellular processes, including cancer. This study leverages machine learning to identify disulfidptosis-related long noncoding RNAs (DRlncRNAs) as potential prognostic biomarkers in KIRC, offering new insights into tumor pathogenesis and treatment avenues.

RESULTS

Our analysis of data from The Cancer Genome Atlas (TCGA) led to the identification of 431 DRlncRNAs correlated with disulfidptosis-related genes. Five key DRlncRNAs (SPINT1-AS1, AL161782.1, OVCH1-AS1, AC131009.3, and AC108673.3) were used to develop a prognostic model that effectively distinguished between low- and high-risk patients with significant differences in overall survival and progression-free survival. The low-risk group had a favorable prognosis associated with a protective immune microenvironment and a better response to targeted drugs. Conversely, the high-risk group displayed aggressive tumor features and poor immunotherapy outcomes. Validation through qRT‒PCR confirmed the differential expression of these DRlncRNAs in KIRC cells compared to normal kidney cells, underscoring their potential functional significance in tumor biology.

CONCLUSIONS

This study established a robust link between disulfidptosis-related lncRNAs and patient prognosis in KIRC, underscoring their potential as prognostic biomarkers and therapeutic targets. The differential expression of these lncRNAs in tumor versus normal tissue further highlights their relevance in KIRC pathogenesis. The predictive model not only enhances our understanding of KIRC biology but also provides a novel stratification tool for precision medicine approaches, improving treatment personalization and outcomes in KIRC patients.

摘要

背景

肾透明细胞癌(KIRC)是肾细胞癌的重要组成部分,尽管免疫疗法取得了进展,但仍具有侵袭性强、预后差的特点。细胞死亡途径二硫键凋亡(disulfidptosis)作为一种关键机制,在包括癌症在内的各种细胞过程中得到了广泛研究。本研究利用机器学习识别与二硫键凋亡相关的长非编码 RNA(DRlncRNAs),作为 KIRC 的潜在预后生物标志物,为肿瘤发病机制和治疗途径提供了新的见解。

结果

我们对来自癌症基因组图谱(TCGA)的数据进行分析,确定了 431 个与二硫键凋亡相关基因相关的 DRlncRNAs。使用五个关键的 DRlncRNAs(SPINT1-AS1、AL161782.1、OVCH1-AS1、AC131009.3 和 AC108673.3)构建了一个预后模型,该模型可以有效地将低风险和高风险患者区分开来,两组患者在总生存期和无进展生存期方面存在显著差异。低风险组患者预后良好,与保护性免疫微环境相关,对靶向药物反应良好。相反,高风险组患者表现出侵袭性肿瘤特征和免疫治疗效果不佳。qRT-PCR 验证证实了这些 DRlncRNAs 在 KIRC 细胞与正常肾细胞中的差异表达,突出了它们在肿瘤生物学中的潜在功能意义。

结论

本研究在 KIRC 中建立了二硫键凋亡相关 lncRNAs 与患者预后之间的紧密联系,强调了它们作为预后生物标志物和治疗靶点的潜力。这些 lncRNAs 在肿瘤与正常组织中的差异表达进一步突出了它们在 KIRC 发病机制中的相关性。该预测模型不仅增强了我们对 KIRC 生物学的理解,还为精准医学方法提供了一种新的分层工具,改善了 KIRC 患者的治疗个性化和预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/681f/11340127/801f0ad1d883/13062_2024_517_Fig1_HTML.jpg

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