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

Abstract

<jats:p>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 &lt; 0.0001), worse histological type of adenocarcinoma (p = 0.0028), later stage (p &lt; 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 &lt; 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.</jats:p>

Review on circular RNAs and new insights into their roles in cancer

“…DdPCR can overcome this shortcoming and be used instead of qPCR for the quantification of circRNA [207] . In addition, it has been shown that plasma levels of secretory circRNAs are detectable by RT-ddPCR in advanced lung cancers [208] .…”

Circular RNAs: Emerging Role in Cancer Diagnostics and Therapeutics

“…Knockdown of circ_0061140 suppressed proliferation and migration in GC cells (Chen Q. et al, 2018). CDR1as expression is upregulated in OC tissues and it correlated with poor prognosis for TNM stages, lymph node metastasis, and reduced OS (Luo Y. H. et al, 2020). CDR1as sponges miR-641 causing up-regulation of ZEB1 and MDM2 expression to promote OC (Luo Y. H. et al, 2020).…”

“…CircRNA_0056616 was upregulated in tissues and plasma of LUAD patients and it was correlated with TNM stage and lymph node metastasis (He F. et al, 2020). Circ_0000190 and circ_000164 were overexpressed in plasma and tissues from LC patients and expression of circ_0000190 was associated with latestage, extra-thoracic metastasis, poor survival, and prognosis (Luo Y. H. et al, 2020). These exosomal circRNAs are easily detectable in liquid biopsy and may serve as potential biomarkers for LC (Luo Y. H. et al, 2020).…”

“…CDR1as expression is upregulated in OC tissues and it correlated with poor prognosis for TNM stages, lymph node metastasis, and reduced OS (Luo Y. H. et al, 2020). CDR1as sponges miR-641 causing up-regulation of ZEB1 and MDM2 expression to promote OC (Luo Y. H. et al, 2020). A large number of circRNAs are misexpressed in primary and metastatic sites of epithelial ovarian carcinoma and their expression exhibits an inverse trend as compared to their linear counterparts in many cancer-related pathways and signaling pathways like NFkB, PI3k/AKT, and TGF-β (Ahmed et al, 2016).…”

The Role of lncRNAs in the Pathobiology and Clinical Behavior of Multiple Myeloma

“…NEAT1 is also upregulated in MM, lung cancer and HCC, but is downregulated in acute promyelocytic leukemia [ 105 ]. Finally, Circ_0000190 is downregulated in MM and gastric cancer, whereas it displays overexpression in lung cancer [ 36 , 37 , 38 ]. These results highlight the cell- and tissue- specificity of lncRNAs, showing that their deregulation—and thus, their potential function—needs to be addressed in each tumor.…”