Endosc Int Open 2015; 03(06): E665-E671
DOI: 10.1055/s-0034-1393077
Original article
© Georg Thieme Verlag KG Stuttgart · New York

Differences in miRNA expression profiles between GIST and leiomyoma in human samples acquired by submucosal tunneling biopsy

Koji Fujita
1   Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan
,
Hideki Kobara
1   Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan
,
Hirohito Mori
1   Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan
,
Shintaro Fujihara
1   Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan
,
Taiga Chiyo
1   Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan
,
Tae Matsunaga
1   Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan
,
Noriko Nishiyama
1   Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan
,
Maki Ayaki
1   Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan
,
Tatsuo Yachida
1   Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan
,
Asahiro Morishita
1   Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan
,
Masao Fujiwara
2   Department of Gastroenterological Surgery, Kagawa University School of Medicine, Kagawa, Japan
,
Keiichi Okano
2   Department of Gastroenterological Surgery, Kagawa University School of Medicine, Kagawa, Japan
,
Yasuyuki Suzuki
2   Department of Gastroenterological Surgery, Kagawa University School of Medicine, Kagawa, Japan
,
Hisakazu Iwama
3   Life Science Research Center, Kagawa University School of Medicine, Kagawa, Japan
,
Tsutomu Masaki
1   Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan
› Author Affiliations
Further Information

Publication History

Publication Date:
23 September 2015 (online)

Background and study aims: Small gastrointestinal stromal tumors (GISTs) rarely have malignant potential with poor prognosis. Using conventional imaging to differentiate between small GISTs and leiomyoma, which often have similar characteristics, is difficult but essential in daily practice. Although some studies have reported on the utility of serum c-kit as a biomarker for non-small GIST and specific miRNA, clinical aspects of such testing are controversial. The aim of this study was to identify differences between small GIST and leiomyoma through the investigation of miRNA expression patterns in human cases.

Patients and methods: MiRNA expression was examined in nine GIST (less than low risk, mean 18 mm in size) samples and seven leiomyoma samples acquired by a novel sampling method, submucosal tunneling biopsy (STB), which produces tumor specimens of submucosal tumor (SMT) without contamination of sufficient size to be examined under direct vision. Total RNA was extracted from these tissues and analyzed for miRNA expression patterns by microarray. Subsequently, real-time quantitative polymerase chain reaction (qPCR) were used to confirm specific miRNA overexpression, comparing GISTs with leiomyomas.

Results: Microarray analysis revealed upregulation of the miR-140 family up to 20 times higher in GISTs than in leiomyomas. Real-time qPCR revealed that the expression level of miR-140-5 p in GISTs was 27.86 times higher than in leiomyomas; miR-140-3 p was 12.24 times higher as well.

Conclusions: The STB method provided suitable SMT samples for miRNA analysis. MiR-140 family members may serve as specific biomarkers to distinguish GIST from leiomyoma.

 
  • References

  • 1 Fletcher CD, Berman JJ, Corless C et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol 2002; 33: 459-465
  • 2 Nilsson B, Bümming P, Meis-Kindblom JM et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era--a population-based study in western Sweden. Cancer 2005; 103: 821-829
  • 3 Franquemont DW. Differentiation and risk assessment of gastrointestinal stromal tumors. Am J Clin Pathol 1995; 103: 41-47
  • 4 Sircar K, Hewlett BR, Huizinga JD et al. Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors. Am J Surg Pathol 1999; 23: 377-389
  • 5 Sarlomo-Rikala M, Kovatich AJ, Barusevicius A et al. CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol 1998; 11: 728-734
  • 6 Yamamoto H, Oda Y. Gastrointestinal stromal tumor: recent advances in pathology and genetics. Pathol Int 2015; 65: 9-18
  • 7 Kakavetsi V. Seum c-kit protein detection as a reliable biomarker for the diagnosis of gastrointestinal stromal tumors. J Mol Biomark Diagn 2014; S6
  • 8 Weiland M, Gao XH, Zhou L et al. Small RNAs have a large impact: circulating microRNAs as biomarkers for human diseases. RNA Biol 2012; 9: 850-859
  • 9 Subramanian S, Lui WO, Lee CH et al. MicroRNA expression signature of human sarcomas. Oncogene 2008; 27: 2015-2026
  • 10 Zavadil J, Ye H, Liu Z et al. Profiling and functional analyses of microRNAs and their target gene products in human uterine leiomyomas. PLoS One 2010; 5: e12362
  • 11 Gits CM, van Kuijk PF, Jonkers MB et al. MiR-17-92 and miR-221/222 cluster members target KIT and ETV1 in human gastrointestinal stromal tumours. Br J Cancer 2013; 109: 1625-1635
  • 12 Ouyang L, Liu P, Yang S et al. A three-plasma miRNA signature serves as novel biomarkers for osteosarcoma. Med Oncol 2013; 30: 340
  • 13 Kobara H, Mori H, Fujiwara S et al. Bloc biopsy by tunneling method using endoscopic submucosal dissection for an upper gastrointestinal submucosal tumor. Endoscopy 2012; 44: E197-E198
  • 14 Kobara H, Mori H, Fujihara S et al. Bloc biopsy by using submucosal endoscopy with a mucosal flap method for gastric subepithelial tumor tissue sampling (with video). Gastrointest Endosc 2013; 77: 141-145
  • 15 Sumiyama K, Gostout CJ, Rajan E et al. Submucosal endoscopy with mucosal flap safety valve. Gastrointest Endosc 2007; 65: 688-694
  • 16 Kato K, Gong J, Iwama H et al. The antidiabetic drug metformin inhibits gastric cancer cell proliferation in vitro and in vivo. Mol Cancer Ther 2012; 11: 549-560
  • 17 Hoda KM, Rodriguez SA, Faigel DO. EUS-guided sampling of suspected GI stromal tumors. Gastrointest Endosc 2009; 69: 1218-1223
  • 18 Sepe PS, Moparty B, Pitman MB et al. EUS-guided FNA for the diagnosis of GI stromal cell tumors: sensitivity and cytologic yield. Gastrointest Endosc 2009; 70: 254-261
  • 19 Kobara H, Mori H, Fujihara S et al. Endoscopically visualized features of gastric submucosal tumors on submucosal endoscopy. Endoscopy 2014; 46: E660-E661
  • 20 Kobara H, Mori H, Rafiq K et al. Analysis of the amount of tissue sample necessary for mitotic count and Ki-67 index in gastrointestinal stromal tumor sampling. Oncol Rep 2015; 33: 215-222
  • 21 Khashab MA, Pasricha PJ. Conquering the third space: challenges and opportunities for diagnostic and therapeutic endoscopy. Gastrointest Endosc 2013; 77: 146-148
  • 22 Inoue H, Minami H, Kobayashi Y et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 2010; 42: 265-271
  • 23 Karlsen TA, Jakobsen RB, Mikkelsen TS et al. microRNA-140 targets RALA and regulates chondrogenic differentiation of human mesenchymal stem cells by translational enhancement of SOX9 and ACAN. Stem Cells Dev 2014; 23: 290-304
  • 24 Jude JA, Dileepan M, Subramanian S et al. miR-140-3p regulation of TNF-α-induced CD38 expression in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2012; 303: L460-L468
  • 25 Song B, Wang Y, Xi Y et al. Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells. Oncogene 2009; 28: 4065-4074