Correlation between the Expression Levels of circulating miR-21 and miR-192 and Clinicopathological Features in Plasma of Patients with Gastric Cancer in Iran




Gastric cancer
Receiver operating characteristic analysis


How to Cite

Asadi Rahmani, F., Ranji, N., & Saeidi Saedi, H. (2021). Correlation between the Expression Levels of circulating miR-21 and miR-192 and Clinicopathological Features in Plasma of Patients with Gastric Cancer in Iran. Iranian Red Crescent Medical Journal, 23(6). (Original work published June 21, 2021)


Background: Gastric cancer (GC) is the most prevalent malignancy worldwide and a common cause of death in Iran. Studies have proved that a variety of dysregulated microRNAs is involved in the development and progression of gastric cancer.

Objectives: The present study aimed to evaluate the expression levels of plasma circulating oncogenic miR-21 and miR-192 and their association with clinical phenotypes of patients with gastric cancer in the north of Iran.

Methods: Clinico-pathological analysis was conducted using a standard protocol and pathological tests. The expression levels of miR-21 and miR-192 were measured using quantitative reverse transcription-polymerase chain reaction in the plasma of twenty pre/post-operative gastric cancer patients and twenty healthy subjects. The receiver operating characteristic (ROC) curve of these microRNAs was analyzed to investigate their diagnosis properties.

Results: The study results indicated that plasma miR-21 expression was significantly associated with tumor stage and helicobacter pylori infection status (P=0.024, P=0.0004, respectively). However, no association was observed between clinic-pathological characteristics and miR-192 expression. The results showed that the plasma levels of miR-21 (P=0.0001) and miR-192 (P=0.0007) were significantly higher in GC patients compared to those in healthy individuals. Furthermore, the ROC analyses yielded the mean ±SD area under the curve (AUC) values of 0.9525±0.03 (P<0.0001) and 0.5925±0.09 (P=0.316) for miR-21 and miR-192, respectively. Pearson regression analysis showed that there was no significant correlation between the expression of miR-21 and miR-192 (P=0.1507).

Conclusion: Based on the obtained results, the expression of the plasma level of miR-21 was significantly higher in gastric cancer patients compared to that in the healthy group. Furthermore, the higher levels of AUC in miR-21 indicated the potential role of miR-21 as a noninvasive biomarker for the prognosis of gastric cancer in the population of the north of Iran.


  1. Ang TL, Fock KM. Clinical epidemiology of gastric cancer. Singapore Med J. 2014;55(12):621-8. doi: 10.11622/smedj.2014174. [PubMed: 25630323].
  2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492. [PubMed: 30207593].
  3. Almasi Z, Rafiemanesh H, Salehiniya H. Epidemiology characteristics and trends of incidence and morphology of stomach cancer in Iran. Asian Pac J Cancer Prev. 2015;16(7):2757-61. doi: 10.7314/apjcp.2015.16.7.2757. [PubMed: 25854359].
  4. Farhood B, Geraily G, Alizadeh A. Incidence and mortality of various cancers in Iran and compare to other countries: a review article. Iran J Public Health. 2018;47(3):309-16. [PubMed: 29845017].
  5. Ishiguro H, Kimura M, Takeyama H. Role of microRNAs in gastric cancer. World J Gastroenterol. 2014;20(19):5694-9. doi: 10.3748/wjg.v20.i19.5694. [PubMed: 24914330].
  6. Pewarchuk ME, Barros-Filho MC, Minatel BC, Cohn DE, Guisier F, Sage AP, et al. Upgrading the repertoire of miRNAs in gastric adenocarcinoma to provide a new resource for biomarker discovery. Int J Mol Sci. 2019;20(22):5697. doi: 10.3390/ijms20225697. [PubMed: 31739401].
  7. Pakizehkar S, Ranji N, Naderi Sohi A, Sadeghizadeh M. Curcumin loaded PEG400-OA nanoparticles: A suitable system to increase apoptosis, decrease migration, and deregulate miR-125b/miR182 in MDA-MB-231 human breast cancer cells. Polymers Adv Technol. 2020;31(8):1793-804. doi: 10.1002/pat.4906.
  8. Macfarlane LA, Murphy PR. MicroRNA: Biogenesis, function and role in cancer. Curr Genomics. 2010;11(7):537-61. doi: 10.2174/138920210793175895. [PubMed: 21532838].
  9. Ishimoto T, Baba H, Izumi D, Sugihara H, Kurashige J, Iwatsuki M, et al. Current perspectives toward the identification of key players in gastric cancer micro RNA dysregulation. Int J Cancer. 2016;138(6):1337-49. doi: 10.1002/ijc.29627. [PubMed: 26041092].
  10. Li M, Zhu M, Li W, Lu Y, Xie X, Wu Y, et al. Alpha-fetoprotein receptor as an early indicator of HBx-driven hepatocarcinogenesis and its applications in tracing cancer cell metastasis. Cancer Lett. 2013;330(2):170-80. doi: 10.1016/j.canlet.2012.11.042. [PubMed: 23211536].
  11. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834-8. doi: 10.1038/nature03702. [PubMed: 15944708].
  12. Wang J, Wang Q, Liu H, Hu B, Zhou W, Cheng Y. MicroRNA expression and its implication for the diagnosis and therapeutic strategies of gastric cancer. Cancer Lett. 2010;297(2):137-43. doi: 10.1016/j.canlet.2010.07.018. [PubMed: 20797817].
  13. Tsujiura M, Ichikawa D, Komatsu S, Shiozaki A, Takeshita H, Kosuga T, et al. Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer. 2010;102(7):1174-9. doi: 10.1038/sj.bjc.6605608. [PubMed: 20234369].
  14. Song J, Bai Z, Han W, Zhang J, Meng H, Bi J, et al. Identification of suitable reference genes for qPCR analysis of serum microRNA in gastric cancer patients. Dig Dis Sci. 2012;57(4):897-904. doi: 10.1007/s10620-011-1981-7. [PubMed: 22198701].
  15. Jiang Y, Zhang M, Guo T, Yang C, Zhang C, Hao J. MicroRNA-21-5p promotes proliferation of gastric cancer cells through targeting SMAD7. Onco Targets Ther. 2018;11:4901. doi: 10.2147/OTT.S163771. [PubMed: 30147341].
  16. Karimi Kurdistani Z, Saberi S, Tsai KW, Mohammadi M. MicroRNA-21: mechanisms of oncogenesis and its application in diagnosis and prognosis of gastric cancer. Arch Iran Med. 2015;18(8):524-36. [PubMed: 26265521].
  17. Chiang Y, Zhou X, Wang Z, Song Y, Liu Z, Zhao F, et al. Expression levels of microRNA-192 and-215 in gastric carcinoma. Pathol Oncol Res. 2012;18(3):585-91. doi: 10.1007/s12253-011-9480-x. [PubMed: 22205577].
  18. Li S, Li F, Niu R, Zhang H, Cui A, An W, et al. Mir-192 suppresses apoptosis and promotes proliferation in esophageal aquamous cell caicinoma by targeting Bim. Int J Clin Exp Pathol. 2015;8(7):8048-56. [PubMed: 26339371].
  19. Xie X, Huang N, Zhang Y, Wei X, Gao M, Li M, et al. MiR-192-5p reverses cisplatin resistance by targeting ERCC3 and ERCC4 in SGC7901/DDP cells. J Cancer. 2019;10(4):1039-51. doi: 10.7150/jca.25814. [PubMed: 30854110].
  20. Liu HS, Xiao HS. MicroRNAs as potential biomarkers for gastric cancer. World J Gastroenterol. 2014;20(34):12007-17. doi: 10.3748/wjg.v20.i34.12007. [PubMed: 25232237].
  21. Wu J, Li G, Wang Z, Yao Y, Chen R, Pu X, et al. Circulating MicroRNA-21 is a potential diagnostic biomarker in gastric cancer. Dis Markers. 2015;2015:435656. doi: 10.1155/2015/435656. [PubMed: 26063956].
  22. Liu L, Chen Q, Lai R, Wu X, Wu X, Liu F, et al. Elevated expression of mature miR-21 and miR-155 in cancerous gastric tissues from Chinese patients with gastric cancer. J Biomed Res. 2010;24(3):187-97. doi: 10.1016/S1674-8301(10)60028-0. [PubMed: 23554630].
  23. Chan SH, Wu CW, Li AF, Chi CW, Lin WC. miR-21 microRNA expression in human gastric carcinomas and its clinical association. Anticancer Res. 2008;28(2A):907-11. [PubMed: 18507035].
  24. Effatpanah H, Yadegarazari R, Karami M, Majlesi A, Shabab N, Saidijam M. Expression analysis of mir-21 and mir-221 in cancerous tissues from Iranian patients with gastric cancer. Iran Biomed J. 2015;19(4):188-93. doi: 10.7508/ibj.2015.04.001. [PubMed: 26209976].
  25. Larki P, Ahadi A. Up-regulation of miR-21, miR-25, miR-93, and miR-106b in gastric cancer. Iran Biomed J. 2018;22(6):367-73. doi: 10.29252/.22.6.367. [PubMed: 29859516].
  26. Shiotani A, Murao T, Kimura Y, Matsumoto H, Kamada T, Kusunoki H, et al. Identification of serum miRNAs as novel non-invasive biomarkers for detection of high risk for early gastric cancer. Br J Cancer. 2013;109(9):2323-30. doi: 10.1038/bjc.2013.596. [PubMed: 24104965].
  27. Xu YJ, Fan Y. MiR-215/192 participates in gastric cancer progression. Clin Transl Oncol. 2015;17(1):34-40. doi: 10.1007/s12094-014-1194-6. [PubMed: 24981590].