An Eight-CircRNA Assessment Model for Predicting Biochemical Recurrence in Prostate Cancer.

An Eight-CircRNA Assessment Model for Predicting Biochemical Recurrence in Prostate Cancer.
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预测前列腺癌生化复发的八环RNA评估模型

DOI:
10.3389/fcell.2020.599494
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发表时间:
2020
影响因子:
5.5
通讯作者:
Lu J
Lu J
中科院分区:
生物学2区
文献类型:
--
作者:
Wang S;Su W;Zhong C;Yang T;Chen W;Chen G;Liu Z;Wu K;Zhong W;Li B;Mao X;Lu J

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前列腺癌(PCa)是男性发病率较高的恶性肿瘤,手术后可能出现生化复发(BCR)。我们的研究旨在使用前列腺癌的环状 RNA 测序数据建立风险评分模型。该数据集来自 GEO 数据库,使用了加拿大 144 名患者的队列。我们去除了低丰度的 circRNA (FPKM < 1),并获得了 546 个 circRNA 用于下一步。使用“survival”和“survminer”R 包通过逻辑回归选择与 BCR 相关的 circRNA。通过“glmnet”R软件包,采用最小绝对收缩和选择器操作(LASSO)回归以及10倍交叉验证和惩罚来构建风险评分模型。我们的风险评分模型总共涉及八个 circRNA(包括 circ_30029、circ_117300、circ_176436、circ_112897、circ_112897、circ_178252、circ_115617、circ_14736 和 circ_17720)。此外,我们采用了高风险评分组和低风险评分组之间差异表达的 mRNA。以下基因本体 (GO) 分析通过 Omicshare Online 工具进行可视化。 GO分析结果显示,肿瘤免疫微环境相关通路显着丰富。使用“CIBERSORT”和“ESTIMATE”R包检测肿瘤浸润免疫细胞,并比较高风险评分组和低风险评分组之间的微环境评分水平。此外,我们验证了八个 circRNA 中的两个(circ_14736 和 circ_17720)循环特征,并通过 qPCR 和 CCK8 体外测试了它们的生物学功能。在 PCa 患者血浆的外泌体中检测到 circ_14736 和 circ_17720。这是第一个利用circRNA建立前列腺癌预后模型的生物信息学研究。这些 circRNA 与 CD8+ T 细胞活性相关,可作为基于 circRNA 的液体活检组合用于疾病预后。
Prostate cancer (PCa) is a high morbidity malignancy in males, and biochemical recurrence (BCR) may appear after the surgery. Our study is designed to build up a risk score model using circular RNA sequencing data for PCa. The dataset is from the GEO database, using a cohort of 144 patients in Canada. We removed the low abundance circRNAs (FPKM < 1) and obtained 546 circRNAs for the next step. BCR-related circRNAs were selected by Logistic regression using the “survival” and “survminer” R package. Least absolute shrinkage and selector operation (LASSO) regression with 10-fold cross-validation and penalty was used to construct a risk score model by “glmnet” R software package. In total, eight circRNAs (including circ_30029, circ_117300, circ_176436, circ_112897, circ_112897, circ_178252, circ_115617, circ_14736, and circ_17720) were involved in our risk score model. Further, we employed differentially expressed mRNAs between high and low risk score groups. The following Gene Ontology (GO) analysis were visualized by Omicshare Online tools. As per the GO analysis results, tumor immune microenvironment related pathways are significantly enriched. “CIBERSORT” and “ESTIMATE” R package were used to detect tumor-infiltrating immune cells and compare the level of microenvironment scores between high and low risk score groups. What’s more, we verified two of eight circRNA’s (circ_14736 and circ_17720) circular characteristics and tested their biological function with qPCR and CCK8 in vitro. circ_14736 and circ_17720 were detected in exosomes of PCa patients’ plasma. This is the first bioinformatics study to establish a prognosis model for prostate cancer using circRNA. These circRNAs were associated with CD8+ T cell activities and may serve as a circRNA-based liquid biopsy panel for disease prognosis.
环状 RNA 测序确定 CircASAP1 是肝细胞癌转移的关键调节因子。
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