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Published in: Medical Oncology 12/2014

01-12-2014 | Original Paper

Three dysregulated microRNAs in serum as novel biomarkers for gastric cancer screening

Authors: Hui Wang, Lei Wang, Zheng Wu, Rong Sun, Haifeng Jin, Jifeng Ma, Lili Liu, Rui Ling, Jun Yi, Ling Wang, Jiefang Bian, Jianghao Chen, Nanlin Li, Shifang Yuan, Jun Yun

Published in: Medical Oncology | Issue 12/2014

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Abstract

Gastric cancer (GC) is one of the most threatening diseases. The symptoms of GC are complex and hard to detect, which also contribute to the poor prognosis of GC. Besides, the current diagnosis for GC is expensive and invasive. Thus, a fast, noninvasive biomarker is urgently needed for GC screening. MicroRNAs (miRNAs) are small noncoding RNAs, which are involved in a great variety of pathological processes, particularly carcinogenesis. MiRNAs are stable in gastric juice, plasma as well as serum, which facilitate it to be a promising biomarker for cancer. In this study, we selected three novel miRNAs, i.e., miR-233, miR-16, and miR-100, to investigate their potential diagnostic value in GC screening. A total of 50 GC patients and 47 healthy controls were involved in this study. Blood serum samples were collected; RNAs were extracted and normalized with U6 snRNA as the internal control; qRT-PCR was performed for relative expression of target miRNAs. Levels of miRNAs expression were compared by Student’s t test for the comparison between two groups, and one-way ANOVA was used for multiple comparisons. The expression of miR-223, miR-16, and miR-100 was all significantly higher in GC patients than controls (all P < 0.001). All the tested miRNAs were manifested to be valuable biomarkers for GC. Relative expression of these miRNAs was significantly correlated with clinical characteristics of GC patients, such as TNM stage (P = 0.036 for miR-223; P < 0.001 for miR-100), metastatic status (P = 0.045 for miR-223; P = 0.031 for miR-16; P = 0.006 for miR-100), tumor size (P = 0.042 for miR-223; P = 0.031 for miR-16; P < 0.001 for miR-100), and differentiation grade (P = 0.036 for miR-223; P = 0.030 for miR-16; P = 0.034 for miR-100). However, in T classification, which considered both tumor size and direct extent of primary tumor, the difference in target miRNAs expression was not significant. In summary, we confirmed the diagnostic value of serum miR-223, miR-16, and miR-100 in GC. Significantly elevated expression of the three miRNAs was also observed in advanced GC patients, which suggested their availability in cancer staging.
Literature
1.
2.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedCrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedCrossRef
4.
go back to reference Ebert MP, Rocken C. Molecular screening of gastric cancer by proteome analysis. Eur J Gastroenterol Hepatol. 2006;18(8):847–53.PubMedCrossRef Ebert MP, Rocken C. Molecular screening of gastric cancer by proteome analysis. Eur J Gastroenterol Hepatol. 2006;18(8):847–53.PubMedCrossRef
5.
6.
go back to reference Rasheed SAK, Teo CR, Beillard EJ, Voorhoeve PM, Casey PJ. microRNA-182 and microRNA-200a control G-protein subunit α-13 (GNA13) expression and cell invasion synergistically in prostate cancer cells. J Biol Chem. 2013;288(11):7986–95.PubMedCentralPubMedCrossRef Rasheed SAK, Teo CR, Beillard EJ, Voorhoeve PM, Casey PJ. microRNA-182 and microRNA-200a control G-protein subunit α-13 (GNA13) expression and cell invasion synergistically in prostate cancer cells. J Biol Chem. 2013;288(11):7986–95.PubMedCentralPubMedCrossRef
7.
go back to reference Valeri N, Braconi C, Gasparini P, Murgia C, Lampis A, Paulus-Hock V, et al. microRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer. Cancer Cell. 2014;25(4):469–83.PubMedCentralPubMedCrossRef Valeri N, Braconi C, Gasparini P, Murgia C, Lampis A, Paulus-Hock V, et al. microRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer. Cancer Cell. 2014;25(4):469–83.PubMedCentralPubMedCrossRef
8.
go back to reference Yang Y, Peng W, Tang T, Xia L, Wang XD, Duan BF, et al. MicroRNAs as promising biomarkers for tumor-staging: evaluation of miR21 miR155 miR29a and miR92a in predicting tumor stage of rectal cancer. Asian Pac J Cancer Prev. 2014;15(13):5175.PubMedCrossRef Yang Y, Peng W, Tang T, Xia L, Wang XD, Duan BF, et al. MicroRNAs as promising biomarkers for tumor-staging: evaluation of miR21 miR155 miR29a and miR92a in predicting tumor stage of rectal cancer. Asian Pac J Cancer Prev. 2014;15(13):5175.PubMedCrossRef
9.
go back to reference Wittekind C, Asamura H, Sobin LH. TNM Atlas. London: John Wiley & Sons; 2014.CrossRef Wittekind C, Asamura H, Sobin LH. TNM Atlas. London: John Wiley & Sons; 2014.CrossRef
10.
go back to reference Cui L, Zhang X, Ye G, Zheng T, Song H, Deng H, et al. Gastric juice microRNAs as potential biomarkers for the screening of gastric cancer. Cancer. 2013;119(9):1618–26.PubMedCrossRef Cui L, Zhang X, Ye G, Zheng T, Song H, Deng H, et al. Gastric juice microRNAs as potential biomarkers for the screening of gastric cancer. Cancer. 2013;119(9):1618–26.PubMedCrossRef
11.
go back to reference Li C, Li JF, Cai Q, Qiu QQ, Yan M, Liu BY, et al. MiRNA-199a-3p in plasma as a potential diagnostic biomarker for gastric cancer. Ann Surg Oncol. 2013;20(3):397–405.CrossRef Li C, Li JF, Cai Q, Qiu QQ, Yan M, Liu BY, et al. MiRNA-199a-3p in plasma as a potential diagnostic biomarker for gastric cancer. Ann Surg Oncol. 2013;20(3):397–405.CrossRef
12.
go back to reference Cai H, Yuan Y, Hao Y-F, Guo T-K, Wei X, Zhang Y-M. Plasma microRNAs serve as novel potential biomarkers for early detection of gastric cancer. Med Oncol. 2013;30(1):1–7.CrossRef Cai H, Yuan Y, Hao Y-F, Guo T-K, Wei X, Zhang Y-M. Plasma microRNAs serve as novel potential biomarkers for early detection of gastric cancer. Med Oncol. 2013;30(1):1–7.CrossRef
15.
go back to reference Ma J, Yao Y, Wang P, Liu Y, Zhao L, Li Z et al. MiR-152 functions as a tumor suppressor in glioblastoma stem cells by targeting Kruppel-like factor 4. Cancer Lett. 2014;355(1):85–95. Ma J, Yao Y, Wang P, Liu Y, Zhao L, Li Z et al. MiR-152 functions as a tumor suppressor in glioblastoma stem cells by targeting Kruppel-like factor 4. Cancer Lett. 2014;355(1):85–95.
16.
17.
go back to reference Crone SG, Jacobsen A, Federspiel B, Bardram L, Krogh A, Lund AH, et al. microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-kappaB by targeting CARD10 and COPS8 in gastric cancer. Mol Cancer. 2012;11:71.PubMedCentralPubMedCrossRef Crone SG, Jacobsen A, Federspiel B, Bardram L, Krogh A, Lund AH, et al. microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-kappaB by targeting CARD10 and COPS8 in gastric cancer. Mol Cancer. 2012;11:71.PubMedCentralPubMedCrossRef
18.
go back to reference Ma L, Chen Y, Zhang B, Liu G. Increased microRNA-223 in Helicobacter pylori-associated gastric cancer contributed to cancer cell proliferation and migration. Biosci Biotechnol Biochem. 2014;78(4):602–8.PubMedCrossRef Ma L, Chen Y, Zhang B, Liu G. Increased microRNA-223 in Helicobacter pylori-associated gastric cancer contributed to cancer cell proliferation and migration. Biosci Biotechnol Biochem. 2014;78(4):602–8.PubMedCrossRef
19.
go back to reference Kang W, Tong JH, Chan AW, Lung RW, Chau SL, Wong QW, et al. Stathmin1 plays oncogenic role and is a target of microRNA-223 in gastric cancer. PLoS One. 2012;7(3):e33919.PubMedCentralPubMedCrossRef Kang W, Tong JH, Chan AW, Lung RW, Chau SL, Wong QW, et al. Stathmin1 plays oncogenic role and is a target of microRNA-223 in gastric cancer. PLoS One. 2012;7(3):e33919.PubMedCentralPubMedCrossRef
20.
go back to reference Li J, Guo Y, Liang X, Sun M, Wang G, De W, et al. microRNA-223 functions as an oncogene in human gastric cancer by targeting FBXW7/hCdc4. J Cancer Res Clin Oncol. 2012;138(5):763–74.PubMedCrossRef Li J, Guo Y, Liang X, Sun M, Wang G, De W, et al. microRNA-223 functions as an oncogene in human gastric cancer by targeting FBXW7/hCdc4. J Cancer Res Clin Oncol. 2012;138(5):763–74.PubMedCrossRef
21.
go back to reference Li X, Zhang Y, Zhang H, Liu X, Gong T, Li M, et al. MiRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res. 2011;9(7):824–33.PubMedCrossRef Li X, Zhang Y, Zhang H, Liu X, Gong T, Li M, et al. MiRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res. 2011;9(7):824–33.PubMedCrossRef
22.
go back to reference Shin VY, Jin H, Ng EK, Cheng AS, Chong WW, Wong CY, et al. NF-kappaB targets miR-16 and miR-21 in gastric cancer: involvement of prostaglandin E receptors. Carcinogenesis. 2011;32(2):240–5.PubMedCrossRef Shin VY, Jin H, Ng EK, Cheng AS, Chong WW, Wong CY, et al. NF-kappaB targets miR-16 and miR-21 in gastric cancer: involvement of prostaglandin E receptors. Carcinogenesis. 2011;32(2):240–5.PubMedCrossRef
23.
go back to reference Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S, et al. MiR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer J Int Du Cancer. 2008;123(2):372–9.CrossRef Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S, et al. MiR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer J Int Du Cancer. 2008;123(2):372–9.CrossRef
24.
go back to reference Sun H, Meng X, Han J, Zhang Z, Wang B, Bai X, et al. Anti-cancer activity of DHA on gastric cancer–an in vitro and in vivo study. Tumour Biol. 2013;34(6):3791–800.PubMedCrossRef Sun H, Meng X, Han J, Zhang Z, Wang B, Bai X, et al. Anti-cancer activity of DHA on gastric cancer–an in vitro and in vivo study. Tumour Biol. 2013;34(6):3791–800.PubMedCrossRef
25.
go back to reference Wang M, Ren D, Guo W, Wang Z, Huang S, Du H, et al. Loss of miR-100 enhances migration, invasion, epithelial-mesenchymal transition and stemness properties in prostate cancer cells through targeting Argonaute 2. Int J Oncol. 2014;45(1):362–72.PubMed Wang M, Ren D, Guo W, Wang Z, Huang S, Du H, et al. Loss of miR-100 enhances migration, invasion, epithelial-mesenchymal transition and stemness properties in prostate cancer cells through targeting Argonaute 2. Int J Oncol. 2014;45(1):362–72.PubMed
26.
go back to reference Peng H, Luo J, Hao H, Hu J, Xie SK, Ren D, et al. microRNA-100 regulates SW620 colorectal cancer cell proliferation and invasion by targeting RAP1B. Oncol Rep. 2014;31(5):2055–62.PubMed Peng H, Luo J, Hao H, Hu J, Xie SK, Ren D, et al. microRNA-100 regulates SW620 colorectal cancer cell proliferation and invasion by targeting RAP1B. Oncol Rep. 2014;31(5):2055–62.PubMed
27.
go back to reference Shi DB, Xing AY, Gao C, Gao P. Expression of microRNA-100 in human gastric cancer. Zhonghua Bing Li Xue Za Zhi Chin J Pathol. 2013;42(1):15–9. Shi DB, Xing AY, Gao C, Gao P. Expression of microRNA-100 in human gastric cancer. Zhonghua Bing Li Xue Za Zhi Chin J Pathol. 2013;42(1):15–9.
28.
go back to reference Mroczek S, Dziembowski A. U6 RNA biogenesis and disease association. Wiley Interdiscip Rev RNA. 2013;4(5):581–92.PubMedCrossRef Mroczek S, Dziembowski A. U6 RNA biogenesis and disease association. Wiley Interdiscip Rev RNA. 2013;4(5):581–92.PubMedCrossRef
Metadata
Title
Three dysregulated microRNAs in serum as novel biomarkers for gastric cancer screening
Authors
Hui Wang
Lei Wang
Zheng Wu
Rong Sun
Haifeng Jin
Jifeng Ma
Lili Liu
Rui Ling
Jun Yi
Ling Wang
Jiefang Bian
Jianghao Chen
Nanlin Li
Shifang Yuan
Jun Yun
Publication date
01-12-2014
Publisher
Springer US
Published in
Medical Oncology / Issue 12/2014
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0298-8

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