Primary tumor microRNA signature predicts recurrence and survival in patients with locally advanced esophageal adenocarcinoma

Abstract

Esophageal adenocarcinoma (EAC) is an aggressive cancer necessitating the development of improved risk stratification tools for personalized care. Previously, microRNAs have been shown to correlate with the progression and prognosis of various cancer types; however, the value in EAC remains largely unexplored. We performed global microRNA profiling on 32 formalin-fixed, paraffin-embedded EAC specimens to identify microRNAs associated with progression. Literature search and pathway analysis further refined output to five significantly deregulated candidate biomarkers. Four of the five microRNAs (miR-652-5p, miR-7-2-3p, miR-3925-3p, and miR-219-3p) were validated by qRT-PCR. Survival outcomes were evaluated in testing set of 26 stage II/III EAC patients to determine the prognostic relevance of the selected microRNAs. In the testing set, miR-652-5p and miR-7-2-3p expressions were significantly associated with progression-free survival (p-value = .00771 and p-value = .00293). The highest area under receiver operating characteristic (ROC) curve was 0.8212 for the combination of miR-652-5p and miR-7-2-3p. Collectively, our findings demonstrated that the miR-652-5p/miR-7-2-3p signature may serve as a promising prognostic marker in patients with locally advanced EAC.

miR-96-5p enhances cell proliferation and invasion via targeted regulation of ZDHHC5 in gastric cancer

“…Several studies have demonstrated that miR-96-5p is overexpressed in various cancers, including colorectal cancer [13], pancreatic carcinoma [14], prostate cancer [15], hepatocellular carcinoma [16], and breast cancer [17], and it is oncogene that promotes cell proliferation. It has been reported that miR-652-5p is associated with non-small cell lung cancer [18], esophageal adenocarcinoma [19], and breast cancer [20], while the mechanism of miR-652-5p was not elaborated. Current research on miR-222-5p has focused on the role of angiogenesis in the endothelium [21,22], and few studies investigated the effect of miR-222-5p in cancers.…”

microRNA‐219‐5p inhibits epithelial‐mesenchymal transition and metastasis of colorectal cancer by targeting lymphoid enhancer‐binding factor 1

“…Several studies have indicated that aberrant expression of miRs, such as miR‐21, miR‐let‐7 and miR‐24, is associated with proliferation, apoptosis, and invasion of CRC cells by targeting corresponding function proteins . As for miR‐219‐5p, it has been reported as a tumor suppressor in gastric cancer, glioblastoma and esophageal adenocarcinoma, and it also works as a negative regulator of cell proliferation in CRC by targeting platelet‐derived growth factor receptor . However, the mechanism between miR‐219‐5p and metastasis of CRC remains unclear.…”

“…(4) Several studies have indicated that aberrant expression of miRs, such as miR-21, miR-let-7 and miR-24, is associated with proliferation, apoptosis, and invasion of CRC cells by targeting corresponding function proteins. (5) As for miR-219-5p, it has been reported as a tumor suppressor in gastric cancer, glioblastoma and esophageal adenocarcinoma, (6)(7)(8) and it also works as a negative regulator of cell proliferation in CRC by targeting platelet-derived growth factor receptor. (9) However, the mechanism between miR-219-5p and metastasis of CRC remains unclear.LEF1, a member of the high mobility group protein family, can activate the transcription of Wnt target genes, such as c-myc, cyclin D1, MMP-1 and MMP-7, by combing with b-catenin and forming the b-catenin/TCF/LEF complex, to regulate cell behavior.…”

The downregulation of putative anticancer target BORIS/CTCFL in an addicted myeloid cancer cell line modulates the expression of multiple protein coding and ncRNA genes

“…Among miRNA downregulated upon BORIS KD, miR-7-2-3p and let-7a-5p stand out with highest fold ( Supplementary Table S4 ). miR-7-2-3p information is presently limited to biomarker surveys [ 91 , 92 ]. The let-7a-5p expression is normally maintained at a relatively stable level [ 93 ], and the three loci that encode it have no direct association with BORIS binding in K562.…”