Abstract
Purpose
Diffuse-type gastric cancer (DGC) carries a poor prognosis. Effective screening is one measure that might improve the prognosis of this disease. An E-cadherin/p53 double-conditional knockout (DCKO) mouse line recapitulates human DGC morphologically and molecularly. Three circulating microRNAs (miRNA) (miR-103, miR-107, miR-194) in DCKO mice have been identified as biomarkers for DGC. We sought to evaluate whether these circulating miRNAs could be used for the detection of human DGC.
Methods
Subjects were 50 patients with DGC. Controls were first-time outpatients at Aichi Cancer Center Hospital, age- and sex-matched, without a cancer diagnosis. Total RNA containing miRNA was extracted from the plasma samples and then reverse-transcribed. The levels of miRNAs in plasma samples were quantitatively determined by real-time RT-PCR. Spiked-in cel-miR-39 was analyzed as a normalization control.
Results
Levels of the three plasma microRNA levels in DGC cases with or without an intestinal component were not significantly different from those in control subjects. The areas under the receiver operating characteristic curve of miR-103, miR-107, and miR-194 were 0.548, 0.563, and 0.512, respectively.
Conclusions
In contrast to the DCKO mouse model, plasma miR-103, miR-107, and miR-194 levels are not altered in DGC and are not suitable for human DGC screening.
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References
Ferlay JSI, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F (2013) GLOBOCAN 2012 v1.1. Cancer incidence and mortality worldwide: IARC CancerBase no. 11. International Agency for Research on Cancer. http://globocan.iarc.fr/. Accessed 9 Sep 2016
Ferlay J et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386. doi:10.1002/ijc.29210
Graziano F, Humar B, Guilford P (2003) The role of the E-cadherin gene (CDH1) in diffuse gastric cancer susceptibility: from the laboratory to clinical practice. Ann Oncol 14:1705–1713
Hamashima C, Shibuya D, Yamazaki H, Inoue K, Fukao A, Saito H, Sobue T (2008) The Japanese guidelines for gastric cancer screening. Jpn J Clin Oncol 38:259–267. doi:10.1093/jjco/hyn017
Inoue M, Tajima K, Hirose K, Hamajima N, Takezaki T, Kuroishi T, Tominaga S (1997) Epidemiological features of first-visit outpatients in Japan: comparison with general population and variation by sex, age, and season. J Clin Epidemiol 50:69–77
Kakiuchi M et al (2014) Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma. Nat Genet 46:583–587. doi:10.1038/ng.2984
Kunz PL, Gubens M, Fisher GA, Ford JM, Lichtensztajn DY, Clarke CA (2012) Long-term survivors of gastric cancer: a California population-based study. J Clin Oncol 30:3507–3515. doi:10.1200/JCO.2011.35.8028
Lauren P (1965) The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 64:31–49
Rotkrua P, Shimada S, Mogushi K, Akiyama Y, Tanaka H, Yuasa Y (2013) Circulating microRNAs as biomarkers for early detection of diffuse-type gastric cancer using a mouse model. Br J Cancer 108:932–940. doi:10.1038/bjc.2013.30
Shimada S et al (2012) Synergistic tumour suppressor activity of E-cadherin and p53 in a conditional mouse model for metastatic diffuse-type gastric cancer. Gut 61:344–353. doi:10.1136/gutjnl-2011-300050
Tajima K, Hirose K, Inoue M, Takezaki T, Hamajima N, Kuroishi T (2000) A model of practical cancer prevention for out-patients visiting a hospital: the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC). Asian Pac J Cancer Prev 1:35–47
Tan IB et al (2011) Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy. Gastroenterology 141:476–485. doi:10.1053/j.gastro.2011.04.042
Yashiro M, Chung YS, Nishimura S, Inoue T, Sowa M (1995) Establishment of two new scirrhous gastric cancer cell lines: analysis of factors associated with disseminated metastasis. Br J Cancer 72:1200–1210
Acknowledgements
The authors thank the doctors, nurses, and technical and administrative staff at ACCH for the daily administration of the HERPACC study, and the staff of the Department of Gastroenterology, Gastrointestinal Surgery, and Clinical Oncology for their support. This study was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, Culture and Technology of Japan, for Cancer Research from the Ministry of Health, Labor and Welfare of Japan, for the Third-Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, and Grant-in-Aid for Young Scientists (B) Grant Number JP26860430. This study was also supported by the Foundation for Promotion of Cancer Research in Japan, and by the Japan Society for the promotion of Science A3 Foresight Program. The grantors were not involved in the study design, subject enrollment, study analysis, interpretation, or decision to submit this manuscript.
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Oze, I., Shimada, S., Nagasaki, H. et al. Plasma microRNA-103, microRNA-107, and microRNA-194 levels are not biomarkers for human diffuse gastric cancer. J Cancer Res Clin Oncol 143, 551–554 (2017). https://doi.org/10.1007/s00432-016-2316-z
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DOI: https://doi.org/10.1007/s00432-016-2316-z