Plasma Level of Circular RNA hsa_circ_0000190 Correlates with Tumor Progression and Poor Treatment Response in Advanced Lung Cancers

被引：51

作者：

Luo, Yung-Hung ^{[1
,2
,3
]}

Yang, Yi-Ping ^{[2
,4
,5
]}

Chien, Chian-Shiu ^{[4
,6
]}

Yarmishyn, Aliaksandr A. ^{[4
]}

Ishola, Afeez Adekunle ^{[4
,7
,8
]}

Chien, Yueh ^{[4
]}

Chen, Yuh-Min ^{[1
,2
,3
]}

Huang, Tsai-Wang ^{[9
]}

Lee, Kang-Yun ^{[10
,11
,12
]}

Huang, Wen-Chien ^{[13
,14
]}

Tsai, Ping-Hsing ^{[4
]}

Lin, Tzu-Wei ^{[4
]}

Chiou, Shih-Hwa ^{[4
,6
]}

Liu, Chao-Yu ^{[2
,15
]}

Chang, Cheng-Chang ^{[16
]}

Chen, Ming-Teh ^{[2
,17
]}

Wang, Mong-Lien ^{[2
,4
,6
,18
]}

机构：

[1] Taipei Vet Gen Hosp, Dept Chest Med, Taipei 112, Taiwan

[2] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan

[3] Natl Yang Ming Univ, Inst Clin Med, Taipei 112, Taiwan

[4] Taipei Vet Gen Hosp, Dept Med Res, Taipei 112, Taiwan

[5] Natl Yang Ming Univ, Sch Pharmaceut Sci, Taipei 112, Taiwan

[6] Natl Yang Ming Univ, Inst Pharmacol, Taipei 112, Taiwan

[7] Natl Yang Ming Univ, Taiwan Int Grad Program Mol Med, Taipei 112, Taiwan

[8] Acad Sinica, Taipei 112, Taiwan

[9] Triserv Gen Hosp, Div Thorac Surg, Dept Surg, Natl Def Med Ctr, Taipei 114, Taiwan

[10] Taipei Med Univ, Taipei Canc Ctr, Taipei 110, Taiwan

[11] Shuang Ho Hosp, Div Pulm Med, Dept Internal Med, New Taipei 235, Taiwan

[12] Taipei Med Univ, Sch Med, Div Pulm Med, Dept Internal Med,Coll Med, Taipei 110, Taiwan

[13] MacKay Mem Hosp, Div Thorac Surg, Dept Surg, Taipei 104, Taiwan

[14] MacKay Med Coll, Dept Med, Taipei 104, Taiwan

[15] Far Eastern Mem Hosp, Div Thorac Surg, Dept Surg, New Taipei 220, Taiwan

[16] Triserv Gen Hosp, Dept Obstet & Gynecol, Natl Def Med Ctr, Taipei 114, Taiwan

[17] Taipei Vet Gen Hosp, Neurol Inst, Dept Neurosurg, Taipei 112, Taiwan

[18] Natl Yang Ming Univ, Inst Food Safety & Hlth Risk Assessment, Taipei 112, Taiwan

来源：

CANCERS | 2020年 / 12卷 / 07期

关键词：

lung cancer; circular RNA; liquid biopsy; droplet digital PCR; programmed death-ligand 1; EXPRESSION; BIOMARKER; ADENOCARCINOMA; HETEROGENEITY; APOPTOSIS; DIAGNOSIS;

D O I：

10.3390/cancers12071740

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Lung cancer (LC) causes the majority of cancer-related deaths. Circular RNAs (circRNAs) were reported to play roles in cancers by targeting pro- and anti-oncogenic miRNAs. However, the mechanisms of circRNAs in LC progression and their prognostic value of treatment response remain unclear. By using next generation sequencing (NGS) of LC cell lines' transcriptomes, we identified highly overexpressed hsa_circ_0000190 and hsa_circ_000164 as potential biomarkers. By using the highly sensitive RT-ddPCR method, these circRNAs were shown to be secreted by cell lines and were detected in human blood. Clinical validation by RT-ddPCR was carried out on 272 (231 LC patients and 41 controls) blood samples. Higher hsa_circ_0000190 levels were associated with larger tumor size (p< 0.0001), worse histological type of adenocarcinoma (p= 0.0028), later stage (p< 0.0001), more distant metastatic organs (p= 0.0039), extrathoracic metastasis (p= 0.0004), and poor survival (p= 0.047) and prognosis. Using liquid biopsy-based RT-ddPCR, we discovered the correlation between increased hsa_circ_0000190 plasma level (p< 0.0001) and higher programmed death-ligand 1 (PD-L1) level in tumor (p= 0.0283). Notably, long-term follow-up of the immunotherapy treated cases showed that upregulated plasma hsa_circ_0000190 level correlated with poor response to systemic therapy and immunotherapy (p= 0.0002, 0.0058, respectively). Secretory circRNAs are detectable in blood by LB-based RT-ddPCR and may serve as blood-based biomarkers to monitor disease progression and treatment efficacy.

引用

页码：1 / 20

页数：22