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Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma

伊富貴雄太広島大学

2020.08.27

概要

Esophageal cancer is one of the most common cancers worldwide and has high mortality [1,
2]. The prognosis of patients with esophageal cancer remains poor despite recent improvements in therapy and perioperative management, and 5-year survival rate remains about 20%,
even in developed countries [3]. One reason for this poor prognosis is that most patients with
esophageal cancer are diagnosed at an advanced stage [4]. In contrast, early stage esophageal
cancer, in particular mucosal cancer is expected cure by endoscopic resection [5, 6]. This substantial discrepancy suggests that a specific diagnostic biomarker could be used for early detection would improvement the prognosis of patients with esophageal cancer. While several
biochemical markers have been investigated, including squamous cell carcinoma antigen [7],
carcinoembryonic antigen [8] and, CYFRA 21–1 [9], their sensitivity has not proved consistently satisfactory across the various stages of esophageal cancer.
MicroRNA(miR)s are classified as small noncoding RNAs (19–25 nucleotides) which regulate the expression of plural numbers of messenger RNAs [10–12]. Cancer cells possess miRs
which have particular function in promoting cancer development or minimizing cancer suppression. miRs also exist in the blood stream as inclusions in exosomes. These circulating
miRs play a role in intercellular communication in the cancer environment and bring about
favorable conditions for cancer invasion and metastasis. Because their expression profiles vary
between cancer patients and healthy individuals, circulating miRs can act as powerful biomarkers in the diagnosis of cancer. Indeed, many researchers have reported their usefulness as
novel biomarkers for several malignant tumors, including esophageal cancer [13–17].
Recent research from deep sequencing represented by the next generation sequencer(NGS)
has revealed that miRs are heterogeneous. Isoforms of miR differ slightly from mature miR by
base length and sequence and are referred to as isomiR. Although the function of isomiR is not
completely understood, they are known to play an important role in cancer development [18,
19]. IsomiRs also exist in the blood with high stability, similarly to mature miRs. We hypothesized that combination of circulating miR and isomiRs detected by NGS might act as novel
biomarkers for malignant tumors. To date, however, few studies examined the usefulness of
miR/isomiRs from blood samples as cancer biomarkers. Here, we aimed to investigate their
application in esophageal squamous cell carcinoma (ESCC) using NGS. ...

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Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma

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