Serum hsa-miR-30e As a Potential Biomarker to Predict the Effect of Neoadjuvant Chemoradiation Therapy in Locally Advanced Rectal Cancer

Abstract

Objective:

To identify serum microRNAs (miRNAs) correlated with response to neoadjuvant chemoradiation therapy (NCRT) in locally advanced rectal cancer (LARC) patients using in silico analyses and laboratory validation studies.

Methods:

The GSE68204 and GSE29298 data sets were analyzed to identify differentially expressed (DE) miRNAs in NCRT responders using the GEO2R Limma package within the R software suite. Then we used quantitative real-time polymerase chain reaction to detect the upregulated target miRNAs in the serum of 20 LARC patients. Logistic regression was used to evaluate the effect of serum miRNA level on response. Gene Ontology and pathway enrichment analyses were performed to predict the corresponding functions of the DE miRNAs. Correlation between the expression of the hub target genes and the abundance of tumor-infiltrating lymphocytes was further investigated.

Results:

hsa-miR-30e and hsa-miR-210 were verified to be upregulated in tumor tissues of NCRT responders. A subsequent liquid biopsy study revealed that serum level of miR-30e significantly increased in NCRT-responsive patients in comparison with nonresponders. Each additional unit of serum hsa-miR-30e level is associated with an increase of 2.47-fold in the incidence of response(odds ratio = 2.47, p = 0.0353). Nine hub target genes of hsa-miR-30e were enriched in pathways including immune regulation. The expression of these hub target genes was correlated with the abundance of tumor-infiltrating lymphocytes.

Conclusion:

In summary, hsa-miR-30e was determined to be upregulated in rectal cancer tissues of NCRT-responders. Further investigations showed that increased serum levels of hsa-miR-30e were associated with an effective NCRT response in LARC patients.