Purpose: To systematically evaluate the potential diagnostic value of MicroRNA for gastric cancer (GC). Methods: The relevant literature was identified in databases such as PubMed, Embase and the Cochrane Library (up to December 25, 2020). Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias. Review Manager 5.4, Meta-Disc 1.4 and STATA (version 15.1) software were performed the Meta-analysis. Results: A total of 5914 patients from 41 studies were ultimately included. The pooled sensitivity (SENS) was 0.79 (95% CI: 0.75–0.82), the pooled specificity (SPEC) was 0.87 (95% CI: 0.82–0.91), the pooled positive likelihood ratio (PLR) was 4.95 (95% CI: 3.81–6.43), the pooled negative likelihood ratio (NLR) was 0.28 (95% CI: 0.24–0.32), the pooled diagnostic odds ratio (DOR) was 20.53 (95% CI: 14.57–28.94), and the area under the curve (AUC) was 0.87 (95% CI: 0.84–0.90). A Deeks’ funnel plot demonstrates no publication bias existed (P=0.40). Meta-regression analysis showed that sample size, sample source and sample type were potential sources of heterogeneity. Conclusions: MicroRNA might be the potential biomarke diagnosing gastric cancer. 

Zheng Han, Yifu Zhang, Huixia Zhu. Diagnostic Value of microRNAs for Gastric Carcinoma: a Meta-Analysis. Frontiers in Medical Science Research (2022) Vol. 4, Issue 6: 17-27. https://doi.org/10.25236/FMSR.2022.040604.

[1] Fu DG. Epigenetic alterations in gastric cancer. Mol Med Rep, 2015,12(3):3223-30. 

[2] Gao Y, Wang Y, Wang X, et al. miR-335-5p suppresses gastric cancer progression by targeting MAPK10. Cancer Cell Int. 2021;21(1):59-71.

[3] Liu L, Wang S, Cao X, et al. Diagnostic value of circulating microRNAs for gastric cancer in Asian populations: a meta-analysis. Tumour Biol. 2014;35(12):11995-2004.

[4]  Chen X, Cui Y, Xie X, et al. Functional role of miR-27b in the development of gastric cancer. Mol Med Rep. 2018;17(4):5081-5087.

[5] Zhou, X, Ji, G, Chen, H, et al. Clinical role of circulating miR-223 as a novel biomarker in early diagnosis of cancer patients. International journal of clinical and experimental medicine. 2018;8(9):16890–16898.

[6] Li WH, Zhou ZJ, Huang TH, et al. Detection of OSR2, VAV3, and PPFIA3 Methylation in the Serum of Patients with Gastric Cancer. Dis Markers. 2016;2016:5780538.

[7] Zhang J, Qiu WQ, Zhu H, et al. HOTAIR contributes to the carcinogenesis of gastric cancer via modulating cellular and exosomal miRNAs level. Cell Death Dis. 2020;11(9):780-795.

[8] Liu HS, Xiao HS. MicroRNAs as potential biomarkers for gastric cancer. World J Gastroenterol. 2014;20(34):12007-12017. 

[9] Shi Y, Chen X, Xi B, et al. SNP rs3202538 in 3'UTR region of ErbB3 regulated by miR-204 and miR-211 promote gastric cancer development in Chinese population. Cancer Cell Int. 2017;39(32):17-81.

[10] Wei S, Peng L, Yang J, et al. Exosomal transfer of miR-15b-3p enhances tumorigenesis and malignant transformation through the DYNLT1/Caspase-3/Caspase-9 signaling pathway in gastric cancer. J Exp Clin Cancer Res. 2020;39(1):32-42.

[11] Zhu Y, Li W, Yang Y, et al. WISP1 indicates poor prognosis and regulates cell proliferation and apoptosis in gastric cancer via targeting AKT/mTOR signaling pathway. Am J Transl Res. 2020;12(11):7297-7311.

[12] Chen H, Pan D, Yang Z, et al. Integrated analysis and knockdown of RAB23 indicate the role of RAB23 in gastric adenocarcinoma. Ann Transl Med. 2019;7(23):745-758.

[13] Atarod S, Norden J, Bibby LA, et al. Differential MicroRNA Expression Levels in Cutaneous Acute Graft-Versus-Host Disease. Front Immunol. 2018;9:1485-1501.

[14] Ma M, Zhao J, Wu Q, et al. MiRNA-545 negatively regulates the oncogenic activity of EMS1 in gastric cancer. Cancer Med. 2018;7(6):2452-2462.

[15] Zhelankin AV, Vasiliev SV, Stonogina DA, et al. Elevated Plasma Levels of Circulating Extracellular miR-320a-3p in Patients with Paroxysmal Atrial Fibrillation. Int J Mol Sci. 2020;21(10):3485-3502.

[16] Lin J, Shen J, Yue H, et al. miRNA1835p.1 promotes the migration and invasion of gastric cancer AGS cells by targeting TPM1. Oncol Rep. 2019;42(6):2371-2381.

[17] Martin-Masot R, Nestares MT, Diaz-Castro J, et al. Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Revie. Nutrients. 2019;11(11):2557-2574.

[18] Li W, Li J, Mu H, et al. MiR-503 suppresses cell proliferation and invasion of gastric cancer by targeting HMGA2 and inactivating WNT signaling pathway. Cancer Cell Int. 2019;19(6):95-106.

[19] Yan W, Qian L, Chen J, et al. Comparison of Prognostic MicroRNA Biomarkers in Blood and Tissues for Gastric Cancer. J Cancer. 2016;7(1):95-106.

[20] Guo Y, Cui X, Zhang Y, et al. Diagnostic and Prognostic Value of Serum miR-296-5p and miR-28-3p in Human Gastric Cancer. Cancer Biother Radiopharm. 2020; 9(4):95-102.

[21] Schaalan M, Mohamed W, Fathy S. MiRNA-200c, MiRNA-139 and ln RNA H19; new predictors of treatment response in H-pylori- induced gastric ulcer or progression to gastric cancer. Microb Pathog. 2020;149:104442.

[22] Ma H, Wang P, Li Y, et al. Decreased expression of serum miR-647 is associated with poor prognosis in gastric cancer. Int J Clin Exp Pathol. 2019;12(7):2552-2558.

[23] Ning J, Jiao Y, Deng X, et al. Correlation between miR-138-5p expression and efficacy of platinum-based chemotherapy in advanced gastric cancer patients. Translational Cancer Research. 2020;9(1):145-154.

[24] Parvaee P, Sarmadian H, Khansarinejad B, et al. Plasma Level of MicroRNAs, MiR-107, MiR-194 and MiR-210 as Potential Biomarkers for Diagnosis Intestinal-Type Gastric Cancer in Human. Asian Pac J Cancer Prev. 2019;20(5):1421-1426.

[25] Chen J, Wu L, Sun Y, et al. Mir-421 in plasma as a potential diagnostic biomarker for precancerous gastric lesions and early gastric cancer. PeerJ. 2019;7:e7002-e7015.

[26] Mohamed WA, Schaalan MF, Ramadan B. The expression profiling of circulating miR-204, miR-182, and lncRNA H19 as novel potential biomarkers for the progression of peptic ulcer to gastric cancer. J Cell Biochem. 2019;120(8):13464-13477.

[27] Ji B, Huang Y, Gu T, et al. Potential diagnostic and prognostic value of plasma long noncoding RNA LINC00086 and miR-214 expression in gastric cancer. Cancer Biomark. 2019;24(2):249-255.

[28] Ghaedi H, Mozaffari MAN, Salehi Z, et al. Co-expression profiling of plasma miRNAs and long nonc28oding RNAs in gastric cancer patients. Gene. 2019;687:135-142.

[29] Bai SY, Ji R, Wei H, et al. Serum miR-551b-3p is a potential diagnostic biomarker for gastric cancer. Turk J Gastroenterol. 2019;30(5):415-419.

[30] Zhao G, Jiang T, Liu Y, et al. Droplet digital PCR-based circulating microRNA detection serve as a promising diagnostic method for gastric cancer. BMC Cancer. 2018;18(1):676-686.

[31] Fan B, Shen C, Wu M, et al. miR-17-92 cluster is connected with disease progression and oxaliplatin/capecitabine chemotherapy efficacy in advanced gastric cancer patients: A preliminary study. Medicine (Baltimore). 2018;97(35):e12007-e12014.

[32] Lario S, Brunet-Vega A, Quilez ME, et al. Expression profile of circulating microRNAs in the Correa pathway of progression to gastric cancer. United European Gastroenterol J. 2018;6(5):691-701.

[33] Huang M, He YR, Liang LC, et al. Circular RNA hsa_circ_0000745 may serve as a diagnostic marker for gastric cancer. World J Gastroenterol. 2017;23(34):6330-6338. 

[34] Li B, Zhang H. Plasma microRNA-320 is a potential diagnostic and prognostic bio-marker in gastric cancer. Int J Clin Exp Pathol. 2017;10(7):7356-7361. 

[35] Li F, Guo Y, Liu J, et al. The significance of elevated plasma expression of microRNA 106b~25 clusters in gastric cancer. PLoS One. 2017;12(5):e0178427.

[36] Jiang X, Wang W, Yang Y, et al. Identification of circulating microRNA signatures as potential noninvasive biomarkers for prediction and prognosis of lymph node metastasis in gastric cancer. Oncotarget. 2017;8(39):65132-65142. 

[37] Liu S, Suo J, Wang C, et al. Prognostic significance of low miR-144 expression in gastric cancer. Cancer Biomark. 2017;20(4):547-552.

[38] Hou CG, Luo XY, Li G. Diagnostic and Prognostic Value of Serum MicroRNA-206 in Patients with Gastric Cancer. Cell Physiol Biochem. 2016;39(4):1512-1520.

[39] Huang S, Wang J, Li J, et al. Serum microRNA expression profile as a diagnostic panel for gastric cancer. Jpn J Clin Oncol. 2016;46(9):811-818.

[40] Shao Y, Ye M, Li Q, et al. LncRNA-RMRP promotes carcinogenesis by acting as a miR-206 sponge and is used as a novel biomarker for gastric cancer. Oncotarget. 2016;7(25):37812-37824.

[41] Tsai MM, Wang CS, Tsai CY, et al. Circulating microRNA-196a/b are novel biomarkers associated with metastatic gastric cancer. Eur J Cancer. 2016;64:137-148.

[42] Zhu W, Zhou K, Zha Y, et al. Diagnostic Value of Serum miR-182, miR-183, miR-210, and miR-126 Levels in Patients with Early-Stage Non-Small Cell Lung Cancer. PLoS One. 2016;11(4):e0153046.

[43] Qiu X, Zhang J, Shi W, et al. Circulating MicroRNA-26a in Plasma and Its Potential Diagnostic Value in Gastric Cancer. PLoS One. 2016;11(3):e0151345.

[44] Zhuang K, Han K, Tang H, et al. Up-Regulation of Plasma miR-23b is Associated with Poor Prognosis of Gastric Cancer. Med Sci Monit. 2016;22:356-361.

[45] Hou X, Zhang M, Qiao H. Diagnostic significance of miR-106a in gastric cancer. Int J Clin Exp Pathol. 2015;8(10):13096-13101. 

[46] Wang D, Fan Z, Liu F, et al. Hsa-miR-21 and Hsa-miR-29 in Tissue as Potential Diagnostic and Prognostic Biomarkers for Gastric Cancer. Cell Physiol Biochem. 2015;37(4):1454-1462.

[47] Huang YK, Yu JC. Circulating microRNAs and long non-coding RNAs in gastric cancer diagnosis: An update and review. World J Gastroenterol. 2015;21(34):9863-9886.

[48] Park JL, Kim M, Song KS, et al. Cell-Free miR-27a, a Potential Diagnostic and Prognostic Biomarker for Gastric Cancer. Genomics Inform. 2015;13(3):70-75.

[49] Liu X, Kwong A, Sihoe A, et al. Plasma miR-940 may serve as a novel biomarker for gastric cancer. Tumour Biol. 2016;37(3):3589-3597.

[50] Jiang L, Li X, Cheng Q, et al. Plasma microRNA might as a potential biomarker for hepatocellular carcinoma and chronic liver disease screening. Tumour Biol. 2015;36(9):7167-7174.

[51] Zeng Q, Jin C, Chen W, et al. Downregulation of serum miR-17 and miR-106b levels in gastric cancer and benign gastric diseases. Chin J Cancer Res. 2014;26(6):711-726.

[52] Fu Z, Qian F, Yang X, et al. Circulating miR-222 in plasma and its potential diagnostic and prognostic value in gastric cancer. Med Oncol. 2014;31(9):164-172.

[53] Tsujiura M, Komatsu S, Ichikawa D, et al. Circulating miR-18a in plasma contributes to cancer detection and monitoring in patients with gastric cancer. Gastric Cancer. 2015;18(2):271-279.

[54] Zhu C, Ren C, Han J, et al. A five-microRNA panel in plasma was identified as potential biomarker for early detection of gastric cancer. Br J Cancer. 2014;110(9):2291-2299.

[55] Li C, Li JF, Cai Q, et al. MiRNA-199a-3p: A potential circulating diagnostic biomarker for early gastric cancer. J Surg Oncol. 2013;108(2):89-92.

[56] Liu H, Zhu L, Liu B, et al. Genome-wide microRNA profiles identify miR-378 as a serum biomarker for early detection of gastric cancer. Cancer Lett. 2012;316(2):196-203.

[57] Li C, Li JF, Cai Q, et al. miRNA-199a-3p in plasma as a potential diagnostic biomarker for gastric cancer. Ann Surg Oncol. 2013;S397-405.

[58] Wang B, Zhang Q. The expression and clinical significance of circulating microRNA-21 in serum of five solid tumors. J Cancer Res Clin Oncol. 2012;138(10):1659-1666.

[59] Song MY, Pan KF, Su HJ, et al. Identification of serum microRNAs as novel non-invasive biomarkers for early detection of gastric cancer. PLoS One. 2012;7(3):e33608.

[60] Zhang WH, Gui JH, Wang CZ, et al. The identification of miR-375 as a potential biomarker in distal gastric adenocarcinoma. Oncol Res. 2012;20(4):139-147.

[61] Lee YM, Kim SH, Kim MS, et al. Epigenetic Role of Histone Lysine Methyltransferase and Demethylase on the Expression of Transcription Factors Associated with the Epithelial-to-Mesenchymal Transition of Lung Adenocarcinoma Metastasis to the Brain. Cancers (Basel). 2020;12(12):3632-3653.