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利用与衰老相关的长非编码 RNA 特征的肾透明细胞肾细胞癌预后模型确定 THBS1-IT1 为多种癌症的潜在预后生物标志物。

Prognostic model of kidney renal clear cell carcinoma using aging-related long noncoding RNA signatures identifies THBS1-IT1 as a potential prognostic biomarker for multiple cancers.

机构信息

Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.

Department of Urology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.

出版信息

Aging (Albany NY). 2023 Sep 13;15(17):8630-8663. doi: 10.18632/aging.204949.

Abstract

Aging is responsible for the main intrinsic triggers of cancers; however, the studies of aging risk factors in cancer animal models and cancer patients are rare and insufficient to be represented in cancer clinical trials. For a better understanding of the complex regulatory networks of aging and cancers, 8 candidate aging related long noncoding RNAs (CarLncs) identified from the healthy aging models, centenarians and their offsprings, were selected and their association with kidney renal clear cell carcinoma (KIRC) was explored by series of cutting edge analyses such as support vector machine (SVM) and random forest (RF) algorithms. Using data downloaded from TCGA and GTEx databases, a regulatory network of CarLncs-miRNA-mRNA was constructed and five genes within the network were screened out as aging related feature genes for developing KIRC prognostic models. After a strict filtering pipeline for modeling, a formula using the transcript per million (TPM) values of feature genes "LncAging_score = 0.008* MMP11 + 0.066* THBS1-IT1 + (-0.014)* DYNLL2 + (-0.030)* RMND5A+ 0.008* PEG10" was developed. ROC analysis and nomogram suggest our model achieves a great performance in KIRC prognosis. Among the 8 CarLncs, we found that was significantly dysregulated in 12 cancer types. A comprehensive pan-cancer analysis demonstrated that is a potential prognostic biomarker in not only KIRC but also multiple cancers, such as LUSC, BLCA, GBM, LGG, MESO, PAAD, STAD and THCA, it was correlated with tumor microenvironment (TME) and tumor immune cell infiltration (TICI) and its high expression was related with poor survival.

摘要

衰老是癌症主要内在触发因素的原因;然而,癌症动物模型和癌症患者的衰老风险因素研究很少且不足以在癌症临床试验中体现。为了更好地理解衰老和癌症的复杂调控网络,从健康衰老模型、百岁老人及其后代中鉴定了 8 个候选衰老相关长非编码 RNA(CarLnc),并通过支持向量机(SVM)和随机森林(RF)算法等一系列前沿分析方法探索了它们与肾透明细胞癌(KIRC)的关联。使用从 TCGA 和 GTEx 数据库下载的数据,构建了 CarLnc-miRNA-mRNA 调控网络,并从网络中筛选出 5 个基因作为与衰老相关的特征基因,用于开发 KIRC 预后模型。经过严格的建模筛选流程,使用特征基因“LncAging_score = 0.008MMP11 + 0.066THBS1-IT1 - (-0.014)*DYNLL2 - (-0.030)RMND5A + 0.008PEG10”的转录本每百万(TPM)值的公式。ROC 分析和列线图表明,我们的模型在 KIRC 预后中表现出色。在这 8 个 CarLnc 中,我们发现在 12 种癌症类型中显著失调。全面的泛癌症分析表明,不仅在 KIRC 中,而且在多种癌症中,如 LUSC、BLCA、GBM、LGG、MESO、PAAD、STAD 和 THCA,都是潜在的预后生物标志物,它与肿瘤微环境(TME)和肿瘤免疫细胞浸润(TICI)相关,其高表达与预后不良相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eec/10522375/8d3121591f40/aging-15-204949-g001.jpg

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