Abstract
Plasma exosomal miRNAs are key regulators of cell-cell interactions associated with several biological functions in patients with cancer. This pilot study aimed to investigate the log2 fold change (log2FC) of the expression of exosomal miRNAs and related mRNAs in the blood of patients with cervical cancer to identify prognostic markers better than those currently available. We sequenced plasma exosomal RNA from 56 blood samples collected from 28 patients with cervical cancer, who had been treated with concurrent chemoradiotherapy (CCRT). Changes in the expression of miRNAs and mRNAs before and after CCRT were represented as log2FC. Their biological functions were studied by miRNA-mRNA network analysis, using ingenuity pathway analysis, after the selection of two groups of miRNAs, each associated with early progression (EP) and metastasis, also described as initial stage. Seven patients experienced EP, three of whom died within four months after progression. Reduced levels of miR-1228-5p, miR-33a-5p, miR-3200-3p, and miR-6815-5p and increased levels of miR-146a-3p in patients with EP revealed unresolved inflammation, with accompanying increased expression of PCK1 and decreased expression of FCGR1A. Increased levels of miR-605-5p, miR-6791-5p, miR-6780a-5p, and miR-6826-5p and decreased levels of miR-16-1-3p (or 15a-3p) were associated with the degree of metastasis and led to the systemic activation of myeloid, endothelial, and epithelial cells, as well as neurons, phagocytes, and platelets. Log2FCs in the expression of miRNAs and mRNAs from plasma exosomes after CCRT are associated with EP and metastasis, reflecting unresolved inflammation and systemic microenvironmental factors, respectively. However, this study, supported by preliminary data insufficient to reach clear conclusions, should be verified in larger prospective cohorts.
Highlights
The prognosis of cervical cancer is estimated based on the initial clinical stage; occasionally, patients with cervical cancer proceed to death earlier than expected.This may occur after three major cancer treatments: surgery, chemotherapy, and radiotherapy (RT) [1,2,3]
early progression (EP) was defined as the observation of new tumor(s) outside the RT field within a year after diagnosis; tumor progression within the RT field or after one year of diagnosis was not defined as EP
Our findings clearly suggested that the log2 fold change (log2 FC) of miRNAs contained within plasma exosomes are associated with EP and metastasis in patients with cervical cancer
Summary
The prognosis of cervical cancer is estimated based on the initial clinical stage; occasionally, patients with cervical cancer proceed to death earlier than expected This may occur after three major cancer treatments: surgery, chemotherapy, and radiotherapy (RT) [1,2,3]. Non-homeostatic states are associated with the co-existence of pro-inflammatory and anti-inflammatory signals, which may result in the abundant secretion of growth factors, high blood glucose levels, and inactivated cell-mediated immunity. Such a systemic environment can be favorable for cancer progression; the association between unresolved inflammatory responses and cancer progression or death still remains undefined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
