Circulating MicroRNAs: A Next-Generation Clinical Biomarker for Digestive System Cancers

Kawaguchi, Tsutomu; Komatsu, Shuhei; Ichikawa, Daisuke; Tsujiura, Masahiro; Takeshita, Hitoshi; Hirajima, Shoji; Miyamae, Mahito; Okajima, Wataru; Ohashi, Takuma; Imamura, Taisuke; Kiuchi, Jun; Konishi, Hirotaka; Shiozaki, Atsushi; Okamoto, Kazuma; Otsuji, Eigo

doi:10.3390/ijms17091459

Cited by 72 publications

(50 citation statements)

References 90 publications

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“…Numerous circulating miRNAs have been identified as potential biomarkers of various cancer types 16,19,25,39,[53][54][55] . Regarding PCa, to date, more than thirty miRNAs have been reported as potentially useful biomarkers 31,33,37,[56][57][58][59] .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, some extracellular miRNAs occur not only through cell lysis but also through active secretion [25][26][27] and can function as intercellular transmitters 19,26,28,29 . Thus, various blood-based miRNAs have been identified, including those in this study, and can be used for cancer detection, monitoring tumor dynamics, and predicting prognosis and chemoresistance [30][31][32][33][34][35][36][37][38][39][40][41][42] . Recently, Kosaka and Ochiya et al suggested a novel mechanism -that miRNAs could facilitate the system of maintenance and surveillance against cancer progression.…”

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confidence: 99%

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Depleted Tumor Suppressor miR-107 in Plasma Relates to Tumor Progression and Is a Novel Therapeutic Target in Pancreatic Cancer

Imamura

Komatsu

Ichikawa

et al. 2017

Journal of the American College of Surgeons

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This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in pancreatic cancer (PCa) patients to clarify their potential as novel biomarkers and therapeutic targets. We used the microRNA array-based approach to select candidates by comparing plasma levels between PCa patients and healthy volunteers. Six down-regulated miRNAs (miR-107, miR-126, miR-451, miR-145, miR-491-5p, and miR-146b-5p) were selected. Small-and large-scale analyses using samples from 100 PCa patients and 80 healthy volunteers revealed that miR-107 was the most down-regulated miRNA in PCa patients compared with healthy volunteers (P < 0.0001; area under the receiver-operating characteristic curve, 0.851). A low miR-107 plasma level was significantly associated with advanced T stage, N stage, and liver metastasis and was an independent factor predicting poor prognosis in PCa patients (P = 0.0424; hazard ratio, 2.95). miR-107 overexpression in PCa cells induced G1/S arrest with the production of p21 and inhibited cell proliferation through the transcriptional regulation of Notch2. In vivo, the restoration and maintenance of the miR-107 plasma level significantly inhibited tumor progression in mice. Depletion of the tumor suppressor miR-107 in plasma relates to tumor progression and poor outcomes. The restoration of the plasma miR-107 level might be a novel anticancer treatment strategy for PCa.Pancreatic cancer (PCa) is the fourth leading cause of cancer-related death in Japan and the United States 1 and the seventh worldwide 2 . PCa is one of the most aggressive cancer types and constitutes a global health problem, with more than 330,000 cancer-related deaths annually 2 . Although perioperative chemo-and/or radiotherapy regimens, surgical techniques and perioperative management have greatly progressed, PCa continues to present an extremely poor prognosis. Even now, the median survival time of PCa patients is 5 to 8 months, and their 5-year survival rate is less than 10%. This is because PCa develops with no symptoms, local invasiveness, or metastases to distant organs in the early stage of its clinical course [3][4][5] . Therefore, novel early diagnostic tools and effective treatment strategies are urgently needed to improve the survival rate of PCa patients.Because understanding the molecular mechanisms of tumorigenesis and identifying clinical biomarkers and molecular targets for PCa contribute to improving the management of this lethal disease, several studies have attempted to detect the biological factors involved in the malignant potential of PCa 6, 7 . Nevertheless, in clinical settings, no molecule has been used as an early diagnostic biomarker, and only a few molecules have been

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Depleted Tumor Suppressor miR-107 in Plasma Relates to Tumor Progression and Is a Novel Therapeutic Target in Pancreatic Cancer

Imamura

Komatsu

Ichikawa

et al. 2017

Journal of the American College of Surgeons

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“…The epigenetic involvement of SST gene silencing in CRC is supported by observations that SST methylation levels in tumor tissues are significantly higher than that in adjacent normal mucosa of CRC patients or normal mucosa from healthy controls (44) and that hypermethylation was found in percentages ranging from 88% to 100% in primary tumours (42,44). (47).…”

Section: Prognostic Role Of Circulating Biomarkersmentioning

confidence: 92%

Epigenetics of colorectal cancer: emerging circulating diagnostic and prognostic biomarkers

Danese

Montagnana

2017

Ann. Transl. Med.

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Colorectal cancer (CRC) is one of the most common cancers worldwide and the second leading cause of cancer-related mortality in western countries. Despite the high incidence, treatment options for advanced CRC remain limited and unsuccessful, resulting in a poor prognosis. Therefore, novel accurate diagnostic, prognostic and predictive biomarkers are clearly and urgently needed to detect advanced colon polyps and early stage CRC and to identify the most effective treatments for specific CRC patients. CRC is known to develop from early premalignant lesions to full blown cancer via a multi-step process involving a series of genetic mutations that accumulate over time. Recent improvement of our understanding of CRC biology and advances in genomic technologies has led to the identification of a variety of epigenetic alterations strongly involved in cancer initiation and progression. Among the epigenetic marks implicated in CRC the most widely studied are the global DNA hypomethylation, the promoter hypermethylation and the miRNAs dysregulations. Many evidence exist that such tumour associated alterations may serve as new potential biomarkers. Moreover, due the non-invasive, objective, and potential reproducible assessment, circulating epigenetic biomarkers have reached increasing attentions in the last few years. In this review, we attempt to analyze the existing most recent literature on the role of circulating DNA methylations and miRNAs alterations in CRC diagnosis and prognosis.

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“…As indicated by the usefulness of cell-free DNA and circulating tumor cells, the concept of "liquid biopsy" through circulating miRNAs may also provide ideal individualized therapeutic strategies for cancer patients and contribute to the development of precision medicine. Indeed, previous studies, including our own, have identified various blood-based miRNA biomarker candidates, which are useful for cancer detection, monitoring tumor dynamics, and predicting malignant potential, prognosis, and chemoresistance in cancer patients [32][33][34][35][36][37][38][39][40][41][42][43][44][45] .…”

Section: Circulating Micrornas Are a Promising Source Of Diagnostic Amentioning

confidence: 99%

Circulating microRNAs as a liquid biopsy: a next-generation clinical biomarker for diagnosis of gastric cancer

Komatsu¹,

Kiuchi²,

Imamura³

et al. 2018

JCMT

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Accumulating evidence has suggested the potential clinical utility of novel body fluid biomarkers, or "liquid biopsy", using circulating tumor cells and cell-free nucleic acids from cancer patients. Noninvasive and reproducible, liquid biopsy could provide the basis for individualized therapeutic strategies by identifying genetic and epigenetic aberrations that are closely associated with cancer initiation and progression. MicroRNAs (miRNAs) are short noncoding RNAs that posttranscriptionally regulate gene expression. They also play important roles in various physiological and developmental processes as oncogenic or tumor-suppressive regulators. Specific miRNA expression signatures have been identified in a number of human cancers. Circulating miRNAs have been detected in plasma and serum, and this in blood has attracted the attention of researchers for their potential as noninvasive biomarkers. Circulating miRNAs have emerged as tumorassociated biomarkers that reflect not only the existence of cancer, but also the dynamics, malignant potential, and drug resistance of tumors. Herein, we review the recent biological and clinical research on the circulating miRNAs of gastric cancer and discuss future perspectives for their clinical applications as a liquid biopsy.

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Circulating MicroRNAs: A Next-Generation Clinical Biomarker for Digestive System Cancers

Cited by 72 publications

References 90 publications

Depleted Tumor Suppressor miR-107 in Plasma Relates to Tumor Progression and Is a Novel Therapeutic Target in Pancreatic Cancer

Depleted Tumor Suppressor miR-107 in Plasma Relates to Tumor Progression and Is a Novel Therapeutic Target in Pancreatic Cancer

Epigenetics of colorectal cancer: emerging circulating diagnostic and prognostic biomarkers

Circulating microRNAs as a liquid biopsy: a next-generation clinical biomarker for diagnosis of gastric cancer

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