Weiwei Chen1,2,3, Wenling Wang2,3. 1. Department of Clinical Medicine, Guizhou Medical University, Guiyang, China. 2. Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, China. 3. Department of Abdominal Oncology, Guizhou Cancer Hospital, Guiyang, China.
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 analysis and laboratory validation studies. Methods: GSE68204 and GSE68204 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. Subsequent liquid-biopsy studies revealed that the serum level of miR-30e was associated with a 2.47-fold increased incidence of NCRT-responsive patients in comparison with nonresponders (p-value = 0.038, Mann-Whitney test). 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 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.
Objective: To identify serum microRNAs (miRNAs) correlated with response to neoadjuvant chemoradiation therapy (NCRT) in locally advanced rectal cancer (LARC) patients using in silico analysis and laboratory validation studies. Methods: GSE68204 and GSE68204 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. Subsequent liquid-biopsy studies revealed that the serum level of miR-30e was associated with a 2.47-fold increased incidence of NCRT-responsive patients in comparison with nonresponders (p-value = 0.038, Mann-Whitney test). 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 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.