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use as biomarkers, either in diagnosis or in prediction/ Other signifi cant miRNAs with dysregulated expression
monitoring of therapeutic responses. This review are miR-16-2 and miR-30e, which were associated with
focuses on the most recent advances in studies on a shorter overall and disease-free survival in all EC
some extensively investigated miRNAs in GI cancers, patients. [25]
particularly with regard to their potential as novel Several studies have demonstrated that miRNAs are
biomarkers or therapeutic targets.
consistently detectable in the circulation. The expression
Esophageal Cancer level of miR-21 was up-regulated and miR-375 was
down-regulated in plasma of ESCC patients compared
The incidence and mortality of esophageal cancer (EC) with healthy controls; patients with high plasma
are high, ranking eighth and sixth respectively, levels of miR-21 had greater vascular invasion and
all types of cancer, affecting more males than showed high correlation with recurrence. [26] A panel
females. Esophageal squamous cell carcinoma (ESCC) of 7 serum miRNAs (miR-10a, miR-22, miR-100,
[13]
and esophageal adenocarcinoma (EAC) are the two main miR-148b, miR-223, miR-133a and miR-127-3p) was
EC subtypes. Due to the potential characteristics of up-regulated in ESCC and could clearly distinguish
invasion and metastasis in esophageal carcinoma cells, stage I/II ESCC patients from controls. [27] Supporting
the overall 5-year survival rate is poor despite advanced the role of miRNAs in the circulation, Zhang et al.
[28]
treatment. [13,14] Recent discoveries have shed new light on have found that miR-31 levels were signifi cantly higher
the involvement of miRNA in EC. [15] than controls in 523 serum ESCC samples. In addition,
miRNAs as novel diagnostic and prognostic patients with higher levels of serum miR-31 had a
biomarkers in EC poorer prognosis for relapse-free survival. miR-1322
was signifi cantly highly expressed in ESCC serum
Guo et al. found aberrant expression of 46 miRNAs in EC and could be used to distinguish ESCC from healthy
[16]
[22]
tissues, of which 7 miRNAs may be used as biomarkers patients. Thus, circulating miRNAs may be used as
to distinguish malignant EC lesions from adjacent normal potential biomarkers, not only for diagnostic, but also
tissue. Moreover, miR-335, miR-181d, miR-25, miR-7 for prognostic and predictive markers in EC.
and miR-495 are associated with the pathological type of Clinical application of microRNAs in EC
EC (fungating vs. medullary). miR-25 and miR-130b are
[29]
associated with the degree of differentiation of EC and Hummel et al. examined the impact of chemotherapy on
miR-103/107 expression level negatively correlated with miRNA expression in EC cells and found that 13 miRNAs
survival rates miR-25 and miR-130b may also be used were deregulated following treatment with cisplatin or
for early diagnosis as well as gene therapy targets for 5-fl uorouracil (5FU). miR-141 was most highly expressed
[17]
EC. Feber et al. found that miR-203 and miR-205 were in the cisplatin-resistant ESCC cell lines, the target
down-regulated compared with normal epithelium in EC, of miR-141 is YAP1, which is an apoptosis-inducing
[30]
while miR-21 was overexpressed in the two types of gene in DNA-damaging agents. miR-296 and
EC. miR-200c, miR-194 and miR-192 were up-regulated miR-27a are overexpressed in EC, and knockdown
in EAC. Mathe et al. have demonstrated that the of miR-296 and miR-27a was found to be capable of
[18]
overexpression of miR-21 in non-cancerous tissue of increasing sensitivity to both P-glycoprotein-related and
ESCC and down-regulation of miR-375 in cancerous P-glycoprotein-non-related drugs, in turn promoting
tissue of EAC with Barrett’s esophagus (BE) were ADR-induced apoptosis in EC cells. [31,32] Overexpression
markedly associated with a worse prognosis. miR-196a of miR-200c signifi cantly correlated with response to
was highly expressed in EAC, BE, benign and malignant chemotherapy, with this effect being associated with the
[33]
junctions and highly malignant tissue and thus be used Akt pathway. miR-148a up-regulation signifi cantly
as a biomarker for screening EC. [18-20] Among others, the increased the sensitivity to chemotherapy in the majority
[34]
overexpression of miR-129 was identifi ed as a signifi cant of cells. miR-200b/200c/429 were up-regulated in
and independent prognostic factor in surgically treated endometrial cancer and EC, and their overexpression
[21]
ESCC patients. The expression level of miR-1322 correlated with resistance to cisplatin treatment. [35]
was higher in ESCC tissue, making it possible to
distinguish ESCC from healthy samples. Expressions Gastric Cancer
[22]
of miR-31 and miR-142-3p correlated with histological Gastric cancer (GC) is the second leading cause of
differentiation, with high miR-142-3p expression being cancer-related death worldwide. Approximately one
associated with poor prognosis. Therefore, this may million new GC cases per year were estimated to have
be a potential independent prognostic ESCC factor. occurred in 2010. Helicobacter pylori infection,
[36]
[23]
Furthermore, expression profi les of miRNAs have been Epstein-Barr virus infection, gastrin levels, germline
found to be altered in progressive stages of EC neoplastic mutations, dietary factors, and other chronic gastric
development, with expression levels of miR-31 conditions are all factors felt to be involved in GC
[24]
and miR-31* being frequently down-regulated in EAC. development. GC is often diagnosed at an advanced

Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 3 ¦ October 15, 2015 ¦ 145