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前列腺癌患者中与预后和放射敏感性相关的衰老相关长链非编码RNA预后指数的鉴定。

Identification of senescence-related lncRNA prognostic index correlating with prognosis and radiosensitivity in prostate cancer patients.

作者信息

Feng Dechao, Li Li, Shi Xu, Zhu Weizhen, Wang Jie, Wu Ruicheng, Li Dengxiong, Wei Wuran, Han Ping

机构信息

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Aging (Albany NY). 2023 Sep 23;15(18):9358-9376. doi: 10.18632/aging.204888.

Abstract

BACKGROUND

An increasing number of studies are shown how crucial a role cellular senescence plays in tumor development. In this study, we developed a senescence-related lncRNA prognostic index (SRLPI) to forecast radiosensitivity and the probability of biochemical recurrence (BCR) in patients with prostate cancer (PCa).

METHODS

PCa cohorts in TCGA and GEO databases were downloaded. Senescence-and prognosis-related lncRNA with differential expression in tumor and normal samples were identified and used to establish the SRLPI score. Mutation landscape, function pathway, tumor stemness and heterogeneity and tumor immune microenvironment were also analyzed. We performed the analysis using R 3.6.3 and the appropriate tools.

RESULTS

A SRLPI score was constructed based on SNHG1 and MIAT in the TCGA cohort. Our classification of PCa patients into high- and low-risk groups was based on the median SRLPI score. When compared to the low-SRLPI group, the high-SRLPI group was more vulnerable to BCR (HR: 3.33). In terms of BCR-free survival and metastasis-free survival, the GSE116918 showed similar findings. Surprisingly, the SRLPI score demonstrated a high level of radiosensitivity for diagnosis (AUC: 0.98). Age, Gleason score, T stage, N stage, positive lymph nodes, and residual tumor were all significantly greater in patients with high SRLPI scores. Furthermore, this score was significantly related to markers of senescence. Protein secretion and androgen response were found to be substantially enriched in the low-SRLPI group, whereas E2F targets were found to be strongly enriched in the high-SRLPI group for pathway analysis. For the tumor microenvironment assessment, B cells, CD8+ T cells, immune score and TIDE score were positively related to SRLPI score while endothelial level was negatively associated with SRLPI score with statistical significance.

CONCLUSIONS

We developed a SRLPI score that was related to prognosis and radiosensitivity and might be helpful in clinical practice.

摘要

背景

越来越多的研究表明细胞衰老在肿瘤发展中起着至关重要的作用。在本研究中,我们开发了一种衰老相关lncRNA预后指数(SRLPI),以预测前列腺癌(PCa)患者的放射敏感性和生化复发(BCR)概率。

方法

下载了TCGA和GEO数据库中的PCa队列。鉴定出在肿瘤和正常样本中差异表达的衰老与预后相关lncRNA,并用于建立SRLPI评分。还分析了突变图谱、功能途径、肿瘤干性和异质性以及肿瘤免疫微环境。我们使用R 3.6.3和适当的工具进行了分析。

结果

基于TCGA队列中的SNHG1和MIAT构建了SRLPI评分。我们根据SRLPI评分中位数将PCa患者分为高风险组和低风险组。与低SRLPI组相比,高SRLPI组更容易发生BCR(HR:3.33)。在无BCR生存期和无转移生存期方面,GSE116918显示出类似的结果。令人惊讶的是,SRLPI评分在诊断方面显示出较高的放射敏感性(AUC:0.98)。高SRLPI评分患者的年龄、Gleason评分、T分期、N分期、阳性淋巴结和残留肿瘤均显著更高。此外,该评分与衰老标志物显著相关。在通路分析中,发现低SRLPI组中蛋白质分泌和雄激素反应显著富集,而高SRLPI组中E2F靶点强烈富集。对于肿瘤微环境评估,B细胞、CD8 + T细胞、免疫评分和TIDE评分与SRLPI评分呈正相关,而内皮水平与SRLPI评分呈负相关,具有统计学意义。

结论

我们开发了一种与预后和放射敏感性相关的SRLPI评分,可能有助于临床实践。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475f/10564441/bb4d806d3836/aging-15-204888-g001.jpg

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