期刊论文详细信息
BMC Clinical Pathology
Expression of serum miR-20a-5p, let-7a, and miR-320a and their correlations with pepsinogen in atrophic gastritis and gastric cancer: a case–control study
Yuan Yuan2  Cai-yun He2  Li-ping Sun2  Qi-Guan Dong1  Qian Xu2 
[1] The Department of Medical Oncology, the General Hospital of Fushun Mining Bureau, Fushun, Liaoning Province 113008, China;Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, the Key Laboratory of Tumor Etiology and Prevention in Liaoning Province, Shenyang, Liaoning Province 110001, China
关键词: Gastric disease;    Pepsinogen;    Biomarker;    Serum microRNA;   
Others  :  1085031
DOI  :  10.1186/1472-6890-13-11
 received in 2012-09-19, accepted in 2013-03-18,  发布年份 2013
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【 摘 要 】

Background

The identification of serial miRNAs targeting the same functional gastric protein could provide new and effective serological biomarkers for the diagnosis of gastric cancer (GC). The aim of this study was to evaluate the potential of miR-20a-5p, let-7a and miR-320a in the diagnosis of AG or GC and the correlation of the three miRNAs with their predicted target molecules PGA, PGC and PGA/PGC ratio.

Methods

The total of 291 patients included 103 controls (CON), 94 with atrophic gastritis (AG) and 94 with GC. The levels of serum miRNAs were detected by quantitative reverse transcription-polymerase chain reaction and serum pepsinogen A (PGA) and C (PGC) were determined by enzyme-linked immunosorbent assays.

Results

Serum miR-320a level decreased through the controls, AG and GC groups which were the cascades of GC development, while there were no significant differences in levels of miR-20a-5p and let-7a among the controls, AG and GC groups. When stratified by gender and age, serum miR-320a expression was lower in female GC patients than in controls (p = 0.035), especially in female GC patients older than 60 years (p = 0.008). For distinguishing female GC patients aged over 60, the area under the receiver operating characteristic curve for miR-320a was 0.699, and the best cut-off point was 4.76 with a sensitivity of 65.2% and specificity of 68.2%. Concerning the correlations between the selected miR-20a-5p, let-7a, miR-320a and PGs, we found that there were positive correlations between all the three and the ratio of PGA/PGC (r = 0.408, 0.255, 0.324; p = <0.001, 0.009, 0.001, respectively), but there was no relationship between the expression of serum miR-20a-5p and its predicted target PGA, or between let-7a and miR-320a and their predicted target PGC. Serum miR-320a was decreased and PGC was increased in the GC group compared with the control group.

Conclusions

Levels of serum miR-320a were lower in female GC patients older than 60 than in controls, which may provide a potential valuable marker for diagnosing older women with GC. The levels of serum miR-20a-5p, let-7a and miR-320a were positively correlated with PGA/PGC, which may indirectly reflect the functional status of the gastric mucosa.

【 授权许可】

   
2013 Xu et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116(2):281-297.
  • [2]He L, Hannon GJ: MicroRNAs: small RNAs with a big role in gene regulation. Nature reviews 2004, 5(7):522-531.
  • [3]Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X: Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008, 18(10):997-1006.
  • [4]Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A: Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008, 105(30):10513-10518.
  • [5]Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE: The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol 2009, 112(1):55-59.
  • [6]Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, Benjamin H, Kushnir M, Cholakh H, Melamed N: Serum microRNAs are promising novel biomarkers. PLoS One 2008, 3(9):e3148.
  • [7]Wang K, Zhang S, Marzolf B, Troisch P, Brightman A, Hu Z, Hood LE, Galas DJ: Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA 2009, 106(11):4402-4407.
  • [8]Liu H, Zhu L, Liu B, Yang L, Meng X, Zhang W, Ma Y, Xiao H: Genome-wide microRNA profiles identify miR-378 as a serum biomarker for early detection of gastric cancer. Cancer Lett 2012, 316(2):196-203.
  • [9]Liu R, Zhang C, Hu Z, Li G, Wang C, Yang C, Huang D, Chen X, Zhang H, Zhuang R: A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis. Eur J Cancer 2011, 47(5):784-791.
  • [10]Wang M, Gu H, Wang S, Qian H, Zhu W, Zhang L, Zhao C, Tao Y, Xu W: Circulating miR-17-5p and miR-20a: molecular markers for gastric cancer. Molecular medicine reports 2012, 5(6):1514-1520.
  • [11]Zhou H, Guo JM, Lou YR, Zhang XJ, Zhong FD, Jiang Z, Cheng J, Xiao BX: Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using microRNA as a marker. Journal of molecular medicine (Berlin, Germany) 2010, 88(7):709-717.
  • [12]Tsujiura M, Ichikawa D, Komatsu S, Shiozaki A, Takeshita H, Kosuga T, Konishi H, Morimura R, Deguchi K, Fujiwara H: Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer 2010, 102(7):1174-1179.
  • [13]Gritti I, Banfi G, Roi GS: Pepsinogens: physiology, pharmacology pathophysiology and exercise. Pharmacol Res 2000, 41(3):265-281.
  • [14]Kageyama T: Pepsinogens, progastricsins, and prochymosins: structure, function, evolution, and development. Cell Mol Life Sci 2002, 59(2):288-306.
  • [15]Ning PF, Liu HJ, Yuan Y: Dynamic expression of pepsinogen C in gastric cancer, precancerous lesions and Helicobacter pylori associated gastric diseases. World J Gastroenterol 2005, 11(17):2545-2548.
  • [16]Sun LP, Gong YH, Wang L, Yuan Y: Serum pepsinogen levels and their influencing factors: a population-based study in 6990 Chinese from North China. World J Gastroenterol 2007, 13(48):6562-6567.
  • [17]Guo J, Miao Y, Xiao B, Huan R, Jiang Z, Meng D, Wang Y: Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues. J Gastroenterol Hepatol 2009, 24(4):652-657.
  • [18]Motoyama K, Inoue H, Takatsuno Y, Tanaka F, Mimori K, Uetake H, Sugihara K, Mori M: Over- and under-expressed microRNAs in human colorectal cancer. Int J Oncol 2009, 34(4):1069-1075.
  • [19]Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 2006, 103(7):2257-2261.
  • [20]Zhu YM, Zhong ZX, Liu ZM: Relationship between let-7a and gastric mucosa cancerization and its significance. World J Gastroenterol 2010, 16(26):3325-3329.
  • [21]Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Zeng YX, Shao JY: MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA (New York, NY 2008, 14(11):2348-2360.
  • [22]Zhang Y, He X, Liu Y, Ye Y, Zhang H, He P, Zhang Q, Dong L, Liu Y, Dong J: microRNA-320a inhibits tumor invasion by targeting neuropilin 1 and is associated with liver metastasis in colorectal cancer. Oncol Rep 2012, 27(3):685-694.
  • [23]Bronisz A, Godlewski J, Wallace JA, Merchant AS, Nowicki MO, Mathsyaraja H, Srinivasan R, Trimboli AJ, Martin CK, Li F: Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320. Nat Cell Biol 2011, 14(2):159-167.
  • [24]Zhang X, Cui L, Ye G, Zheng T, Song H, Xia T, Yu X, Xiao B, Le Y, Guo J: Gastric juice microRNA-421 is a new biomarker for screening gastric cancer. Tumour Biol 2012, 33(6):2349-2355.
  • [25]Lauren P: 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 1965, 64:31-49.
  • [26]Gong YH, Sun LP, Jin SG, Yuan Y: Comparative study of serology and histology based detection of Helicobacter pylori infections: a large population-based study of 7,241 subjects from China. Eur J Clin Microbiol Infect Dis 2010, 29(7):907-911.
  • [27]He CY, Sun LP, Gong YH, Xu Q, Dong NN, Yuan Y: Serum pepsinogen II: a neglected but useful biomarker to differentiate between diseased and normal stomachs. J Gastroenterol Hepatol 2011, 26(6):1039-1046.
  • [28]Cheng Y, Tan N, Yang J, Liu X, Cao X, He P, Dong X, Qin S, Zhang C: A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci (Lond) 2010, 119(2):87-95.
  • [29]Ji X, Takahashi R, Hiura Y, Hirokawa G, Fukushima Y, Iwai N: Plasma miR-208 as a biomarker of myocardial injury. Clin Chem 2009, 55(11):1944-1949.
  • [30]Zhu W, Qin W, Atasoy U, Sauter ER: Circulating microRNAs in breast cancer and healthy subjects. BMC research notes 2009, 2:89. BioMed Central Full Text
  • [31]Tanaka M, Oikawa K, Takanashi M, Kudo M, Ohyashiki J, Ohyashiki K, Kuroda M: Down-regulation of miR-92 in human plasma is a novel marker for acute leukemia patients. PLoS One 2009, 4(5):e5532.
  • [32]Hussein FK, Nizar B, Mehdi N, Philippe L, Mohammad FK, Rabih B, Eva H, Ahmad D, Nader H, Rim ED: Circulating miR-150 and miR-342 in plasma are novel potential biomarkers for acute myeloid leukemia. J Transl Med 2013, 11(1):31. BioMed Central Full Text
  • [33]Sepramaniam S, Armugam A, Lim KY, Karolina DS, Swaminathan P, Tan JR, Jeyaseelan K: MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia. J Biol Chem 2010, 285(38):29223-29230.
  • [34]Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell JT, Jiang J, Schmittgen TD, Patel T: Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology 2006, 130(7):2113-2129.
  • [35]Chen L, Yan HX, Yang W, Hu L, Yu LX, Liu Q, Li L, Huang DD, Ding J, Shen F: The role of microRNA expression pattern in human intrahepatic cholangiocarcinoma. J Hepatol 2009, 50(2):358-369.
  • [36]Sun JY, Huang Y, Li JP, Zhang X, Wang L, Meng YL, Yan B, Bian YQ, Zhao J, Wang WZ: MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting beta-catenin. Biochem Biophys Res Commun 2012, 420(4):787-792.
  • [37]Diakos C, Zhong S, Xiao Y, Zhou M, Vasconcelos GM, Krapf G, Yeh RF, Zheng S, Kang M, Wiencke JK: TEL-AML1 regulation of survivin and apoptosis via miRNA-494 and miRNA-320a. Blood 2010, 116(23):4885-4893.
  • [38]Broutet N, Plebani M, Sakarovitch C, Sipponen P, Megraud F: Pepsinogen A, pepsinogen C, and gastrin as markers of atrophic chronic gastritis in European dyspeptics. Br J Cancer 2003, 88(8):1239-1247.
  • [39]Webb PM, Hengels KJ, Moller H, Newell DG, Palli D, Elder JB, Coleman MP, De Backer G, Forman D: The epidemiology of low serum pepsinogen A levels and an international association with gastric cancer rates. EUROGAST Study Group. Gastroenterology 1994, 107(5):1335-1344.
  • [40]Sangokoya C, Telen MJ, Chi JT: microRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease. Blood 2010, 116(20):4338-4348.
  • [41]Liu Z, Xiao B, Tang B, Li B, Li N, Zhu E, Guo G, Gu J, Zhuang Y, Liu X: Up-regulated microRNA-146a negatively modulate Helicobacter pylori-induced inflammatory response in human gastric epithelial cells. Microbes and infection / Institut Pasteur 2010, 12(11):854-863.
  • [42]Landskroner-Eiger S, Moneke I, Sessa WC: miRNAs as Modulators of Angiogenesis. Cold Spring Harbor perspectives in medicine 2013., 3(2)
  • [43]Feng Y, Zhang X, Graves P, Zeng Y: A comprehensive analysis of precursor microRNA cleavage by human Dicer. RNA New York, NY 2012, 18(11):2083-2092.
  • [44]Nasrollahzadeh D, Aghcheli K, Sotoudeh M, Shakeri R, Persson EC, Islami F, Kamangar F, Abnet CC, Boffetta P, Engstrand L: Accuracy and cut-off values of pepsinogens I, II and gastrin 17 for diagnosis of gastric fundic atrophy: influence of gastritis. PLoS One 2011, 6(10):e26957.
  • [45]Leja M, Kupcinskas L, Funka K, Sudraba A, Jonaitis L, Ivanauskas A, Janciauskas D, Kiudelis G, Chiu HM, Lin JT: The validity of a biomarker method for indirect detection of gastric mucosal atrophy versus standard histopathology. Dig Dis Sci 2009, 54(11):2377-2384.
  • [46]Graham DY, Nurgalieva ZZ, El-Zimaity HM, Opekun AR, Campos A, Guerrero L, Chavez A, Cardenas V: Noninvasive versus histologic detection of gastric atrophy in a Hispanic population in North America. Clin Gastroenterol Hepatol 2006, 4(3):306-314.
  • [47]Kang JM, Kim N, Yoo JY, Park YS, Lee DH, Kim HY, Lee HS, Choe G, Kim JS, Jung HC: The role of serum pepsinogen and gastrin test for the detection of gastric cancer in Korea. Helicobacter 2008, 13(2):146-156.
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