MicroRNAs as Potential Biomarkers for Chemoresistance in Adenocarcinomas of the Esophagogastric Junction

Abstract

Concerning adenocarcinomas of the esophagogastric junction, neoadjuvant chemotherapy is regularly implemented, but patients’ response varies greatly, with some cases showing no therapeutic effect, being deemed as chemoresistant. Small, noncoding RNAs (miRNAs) have evolved as key players in biological processes, including malignant diseases, often promoting tumor growth and expansion. In addition, specific miRNAs have been implicated in the development of chemoresistance through evasion of apoptosis, cell cycle alterations, and drug target modification. We performed a retrospective study of 33 patients receiving neoadjuvant chemotherapy by measuring their miRNA expression profiles. Histologic tumor regression was evaluated using resection specimens, while miRNA profiles were prepared using preoperative biopsies without prior therapy. A preselected panel of 96 miRNAs, known to be of importance in various malignancies, was used to test for significant differences between responsive (chemosensitive) and nonresponsive (chemoresistant) cases. The cohort consisted of 12 nonresponsive and 21 responsive cases with the following 4 miRNAs differentially expressed between both the groups: hsa-let-7f-5p, hsa-miRNA-221-3p, hsa-miRNA-31-5p, and hsa-miRNA-191-5p. The former 3 showed upregulation in chemoresistant cases, while the latter showed upregulation in chemosensitive cases. In addition, significant correlation between high expression of hsa-miRNA-194-5p and prolonged survival could be demonstrated (p value <0.0001). In conclusion, we identified a panel of 3 miRNAs predicting chemoresistance and a single miRNA contributing to chemosensitivity. These miRNAs might function as prognostic biomarkers and enable clinicians to better predict the effect of one or more reliably select patients benefitting from (neoadjuvant) chemotherapy.

Oxaliplatin resistance in colorectal cancer enhances TRAIL sensitivity via death receptor 4 upregulation and lipid raft localization

“…While changes in death receptor expression were insignificant at a transcriptional level, studies have demonstrated that chemoresistance can alter receptor abundance via mechanisms of translational regulation ( Si et al, 2019 ; Just et al, 2019 ). Confocal microscopy showed that oxaliplatin-resistant cells have increased DR4 in both HCT116 ( Figure 3A ) and SW620 ( Figure 3B ) cell lines.…”

“…Interestingly, DR4 augmentation appears to be independent from transcriptional upregulation as there was no significant change in mRNA expression between OxR and parental cell lines. Increasing evidence demonstrates that chemoresistance affects small non-coding microRNA (miRNA) expression, which modulates transcriptional and translational processes ( Si et al, 2019 ; Just et al, 2019 ). More specifically, studies have shown that oxaliplatin treatment and subsequent resistance in CRC cells alter miRNA expression, affecting signaling pathways within p53, epithelial-to-mesenchymal transition, and cell migration ( Tanaka et al, 2015 ; Gasiulė et al, 2019 ; Evert et al, 2018 ).…”

Oxaliplatin Resistance in Colorectal Cancer Enhances TRAIL Sensitivity Via Death Receptor 4 Upregulation and Lipid Raft Localization

“…While changes in death receptor expression were insignificant at a transcriptional level, studies have demonstrated that chemoresistance can alter receptor abundance via mechanisms of translational regulation (30,31). Confocal microscopy showed that oxaliplatin-resistant cells have increased DR4 in both HCT116 ( Fig 3A ) and SW620 ( Fig.…”

Circulating let-7f-5p improve risk prediction of prostate cancer in patients with benign prostatic hyperplasia

“…The role of let-7f-5p acted as biomarker was also explored. A previous study revealed that let-7f-5p was a prognostic biomarker for chemoresistance in adenocarcinomas of the esophagogastric junction [30]. In addition, Marcia et al found that let-7f-5p combined with other four miRNAs showed high diagnostic accuracy for Parkinson's disease [31].…”