Identification of CDK6 and RHOU in Serum Exosome as Biomarkers for the Invasiveness of Non-functioning Pituitary Adenoma

Yu Shan; Wang Xiaoshuang; Cao Kaican; Bao Xinjie; Yu Jia

doi:10.24920/003585

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Identification of CDK6 and RHOU in Serum Exosome as Biomarkers for the Invasiveness of Non-functioning Pituitary Adenoma

Chinese Medical Sciences Journal Vol. 34, Issue 3, Pages: 168-176(2019)

Original Article | Updated：2024-04-10

- Identification of CDK6 and RHOU in Serum Exosome as Biomarkers for the Invasiveness of Non-functioning Pituitary Adenoma
- Affiliations：
  
  1. 1 State Key Laboratory of Medical Molecular Biology & Key Laboratory of RNA and Hematopoietic Regulation & Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
  2. 2 Department of Thoracic Surgery, Nanfang Hospital, Guangzhou 510515, China
  3. 3 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
- Author bio：
  
  *Xinjie Bao, Tel: 86-18001182406, E-mail: xinjieabao@163.com;
  Jia Yu, Tel: 86-10-69156423, E-mail: j-yu@ibms.pumc.edu.cn
- Funds：
- DOI：10.24920/003585
  CLC：
- Received：22 May 2019，
  
  Published Online：22 May 2019，
  
  Published：22 May 2019
- Accepted：
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Yu Shan, Wang Xiaoshuang, Cao Kaican, et al. Identification of CDK6 and RHOU in Serum Exosome as Biomarkers for the Invasiveness of Non-functioning Pituitary Adenoma[J]. Chinese medical sciences journal, 2019, 34(3): 168-176.
DOI：

Yu Shan, Wang Xiaoshuang, Cao Kaican, et al. Identification of CDK6 and RHOU in Serum Exosome as Biomarkers for the Invasiveness of Non-functioning Pituitary Adenoma[J]. Chinese medical sciences journal, 2019, 34(3): 168-176. DOI： 10.24920/003585.

摘要

目的

探索无功能垂体腺瘤（non-functioning pituitary adenomas

NF-PAs）侵袭性的循环分子标志物。

方法

提取侵袭性NF-PAs（invasive NF-PAs

INF-PAs）和非侵袭性NF-PAs（noninvasive NF-PAs

NNF-PAs）患者外周血血清外泌体RNA

采用数字PCR检测候选基因的表达

检验分析其表达差异。同时利用基因表达值建立受试者工作特征曲线（receiver operating characteristic

ROC）

找出阈值

并计算该阈值区分INF-PAs的正确率、灵敏度、特异度和精度

以评估目的基因对侵袭性的诊断效果。

结果

CDK6和RHOU mRNA在INF-PAs中显著上调。ROC曲线显示:CDK6的曲线下面积为0.772（95%

:0.600-0.943

=0.005）

区分INF-PAs的准确率为77.27%

灵敏度为83.33%

特异度为75.00%

精度为55.56%。RHOU的AUC为0.757（95%

:0.599-0.915

=0.007）

区分准确率为72.73%

灵敏度为83.33%

特异度为68.75%

精度为50.00%。CDK6和RHOU mRNA在NF-PAs患者血清外泌体中的含量呈正相关（

=0.935

0.001）。同时用两个基因的阈值作为预测指标

得到的区分准确率为81.82%

灵敏度为83.33%

特异度为81.25%

精度为62.50%。

结论

血清外泌体中的CDK6和RHOU mRNA分子可作为诊断NF-PA侵袭性的标志物

使用两基因的双阈值诊断可提高准确率、特异度和精度。该结果提示了NF-PAs侵袭性的分子机制

并对侵袭性NF-PAs的早期临床诊断和预后具有重要意义。

Abstract

Objective

To explore circulating biomarkers for screening the invasiveness of non-functioning pituitary adenomas (NF-PAs).

Methods

The exosomal RNAs were extracted from serum of patients with invasive NF-PA (INF-PA) or noninvasive NF-PA (NNF-PA). Droplet digital PCR was adapted to detect the mRNA expression of candidate genes related to tumor progression or invasion

such as cyclin dependent kinase 6 (CDK6)

ras homolog family member U (RHOU)

and spire type actin nucleation factor 2 (SPIRE2). Student’s

-test was used to analyze the statistical difference in the mRNA expression of candidate genes between the two groups. Receiver operating characteristic (ROC) curve was used to establish a model for predicting the invasiveness of NF-PAs. The accuracy

sensitivity

specificity and precision of the model were then obtained to evaluate the diagnostic performance.

Results

CDK6 (0.2600±0.0912

. 0.1789±0.0628

=3.431

=0.0013) and RHOU mRNA expressions (0.2696±0.1118

. 0.1788±0.0857

=2.946

=0.0052) were upregulated in INF-PAs patients’ serum exosomes as compared to NNF-PAs. For CDK6

the area under the ROC curve (AUC) was 0.772 (95%

: 0.600-0.943

=0.005)

the accuracy

sensitivity

specificity and precision were 77.27%

83.33%

75.00% and 55.56% to predict the invasiveness of NF-PAs. For RHOU

the AUC was 0.757 (95%

: 0.599-0.915

=0.007)

the accuracy

sensitivity

specificity and precision were 72.73%

83.33%

68.75% and 50.00%. In addition

the mRNA levels of CDK6 and RHOU in serum exosomes were significantly positively correlated (

=0.935

0.001). After combination of the cut-off scores of the two genes

the accuracy

sensitivity

specificity and precision were 81.82%

83.33%

81.25% and 62.50%.

Conclusions

CDK6 and RHOU mRNA in serum exosomes can be used as markers for predicting invasiveness of NF-PAs. Combination of the two genes performs better in distinguishing INF-PAs from NNF-PAs. These results indicate CDK6 and RHOU play important roles in the invasiveness of NF-PAs

and the established diagnostic method is valuable for directing the clinical screening and postoperative treatment.

关键词

Keywords

references

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