Skip to main content

Advertisement

SpringerLink
Log in

Clinical significance of serum miR-223, miR-25 and miR-375 in patients with esophageal squamous cell carcinoma

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Changes in the expression profiles of microRNAs (miRNAs) have been found in many cancers. The study was aimed to investigate the expression of miR-25, miR-223, and miR-375 in the serum of patients with esophageal squamous cell carcinoma (ESCC) and its effect on survival outcome. We examined the expression levels of miR-25, miR-223, and miR-375 in 20 pairs of ESCC cancer and matched paracancerous tissues, serum samples from 94 healthy volunteers and 194 patients with ESCC using quantitative reverse transcription polymerase chain reaction, and analyzed the relationship between expressions of serum miR-25, miR-223, and miR-375 and ESCC clinicopathological parameters as well as survival. Expressions of miR-25 and miR-223 were significantly increased in ESCC tissues compared with paracancerous tissues (P = 0.008 and 0.009, respectively), whereas the expression of miR-375 was significantly decreased in ESCC tissues compared with paracancerous tissues (P = 0.006). Expressions of serum miR-25 and miR-223 were significantly higher in ESCC patients than those in healthy controls, and, inversely, expression of serum miR-375 was significantly lower in ESCC patients than those in healthy controls (P = 0.007). High expression of serum miR-25 was significantly associated with lymph node metastasis (P = 0.01). Survival analysis showed that high expression of serum miR-223 and low expression of serum miR-375 were associated with poor survival in ESCC patients [hazard ratio (HR) = 1.717, 95 % confidence intervals (CI) 1.139–2.588, P = 0.01; HR = 1.750, 95 % CI 1.111–2.756, P = 0.016, respectively). Furthermore, Patients with high miR-223 and low miR-375 expression had higher risk of death than those with low miR-223 and high miR-375 expression (HR = 3.599, 95 % CI 1.800–7.195, P = 2.92 × 10−4). In conclusion, miR-25, miR-223, and miR-375 were abnormally expressed in ESCC tissues and sera. Serum miR-223 and miR-375 are potential prognostic biomarkers for ESCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Jemal A (2011) Global cancer statistics (vol 61, pg 69, 2011). Ca-Cancer J Clin 61(2):134

    Article  Google Scholar 

  2. Portale G, Hagen JA, Peters JH, Chan LS, DeMeester SR, Gandamihardja TA, DeMeester TR (2006) Modern 5-year survival of resectable esophageal adenocarcinoma: single institution experience with 263 patients. J Am Coll Surg 202(4):588–596

    Article  PubMed  Google Scholar 

  3. Hirst J, Smithers BM, Gotley DC, Thomas J, Barbour A (2011) Defining cure for esophageal cancer: analysis of actual 5-Year survivors following esophagectomy. Ann Surg Oncol 18(6):1766–1774

    Article  PubMed  Google Scholar 

  4. Lee DH, Kim HR, Kim DK, Park SI, Kim YH (2013) Outcomes of cervical lymph node recurrence in patients with esophageal squamous cell carcinoma after esophagectomy with two-field lymph node dissection. J Thorac Cardiovasc Surg 146(2):365–371

    Article  PubMed  Google Scholar 

  5. Kosuga T, Shiozaki A, Fujiwara H, Ichikawa D, Okamoto K, Komatsu S, Otsuji E (2011) Treatment outcome and prognosis of patients with lymph node recurrence of thoracic esophageal squamous cell carcinoma after curative resection. World J Surg 35(4):798–804

    Article  PubMed  Google Scholar 

  6. Hofheinz RD, Al-Batran SE, Ridwelski K, Gorg C, Wehle K, Birth M, Fetscher S, Scheiber H, Lukan N, Lordick F (2010) Population-based patterns of care in the first-line treatment of patients with advanced esophagogastric adenocarcinoma in Germany. Onkologie 33(10):512–518

    Article  PubMed  Google Scholar 

  7. Zhu Y, Fu L, Chen L, Qin YR, Liu H, Xie F, Zeng T, Dong SS, Li J, Li Y, Dai Y, Xie D, Guan XY (2013) Downregulation of the novel tumor suppressor DIRAS1 predicts poor prognosis in esophageal squamous cell carcinoma. Cancer Res 73(7):2298–2309

    Article  CAS  PubMed  Google Scholar 

  8. Zhai J, Yang X, Zhang Y, Qi Q, Hu J, Wang Q (2013) Reduced expression levels of the death-associated protein kinase and E-cadherin are correlated with the development of esophageal squamous cell carcinoma. Exp Ther Med 5(3):972–976

    PubMed Central  PubMed  Google Scholar 

  9. Ohtsuka M, Yamamoto H, Masuzawa T, Takahashi H, Uemura M, Haraguchi N, Nishimura J, Hata T, Yamasaki M, Miyata H, Takemasa I, Mizushima T, Takiguchi S, Doki Y, Mori M (2013) C4.4A expression is associated with a poor prognosis of esophageal squamous cell carcinoma. Ann Surg Oncol 20(8):2699–2705

    Article  PubMed  Google Scholar 

  10. Ong CA, Lao-Sirieix P, Fitzgerald RC (2010) Biomarkers in Barrett’s esophagus and esophageal adenocarcinoma: predictors of progression and prognosis. World J Gastroenterol 16(45):5669–5681

    Article  PubMed  Google Scholar 

  11. Tie J, Fan DM (2011) Big roles of microRNAs in tumorigenesis and tumor development. Histol Histopathol 26(10):1353–1361

    CAS  PubMed  Google Scholar 

  12. Schickel R, Boyerinas B, Park SM, Peter ME (2008) MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene 27(45):5959–5974

    Article  CAS  PubMed  Google Scholar 

  13. Fan AC, Goldrick MM, Ho J, Liang Y, Bachireddy P, Felsher DW (2008) A quantitative PCR method to detect blood microRNAs associated with tumorigenesis in transgenic mice. Mol Cancer 7:74

    Article  PubMed Central  PubMed  Google Scholar 

  14. Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120(1):15–20

    Article  CAS  PubMed  Google Scholar 

  15. Kent OA, Mendell JT (2006) A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. Oncogene 25(46):6188–6196

    Article  CAS  PubMed  Google Scholar 

  16. Vannini I, Fanini F, Fabbri M (2013) MicroRNAs as lung cancer biomarkers and key players in lung carcinogenesis. Clin Biochem 46(10–11):918–925

    Article  CAS  PubMed  Google Scholar 

  17. Faltejskova P, Svoboda M, Srutova K, Mlcochova J, Besse A, Nekvindova J, Radova L, Fabian P, Slaba K, Kiss I, Vyzula R, Slaby O (2012) Identification and functional screening of microRNAs highly deregulated in colorectal cancer. J Cell Mol Med 16(11):2655–2666

    Article  CAS  PubMed  Google Scholar 

  18. Li Q, Zou C, Huang H, Jin J, Han Z, Zhang L, Xiao H, Wei H, Tang Q, Zhang C, Tao J, Wang X, Gao X (2013) MicroRNA-25 functions as a potential tumor suppressor in colon cancer by targeting Smad7. Cancer Lett 335(1):168–174

    Article  CAS  PubMed  Google Scholar 

  19. Kong KL, Kwong DLW, Chan THM, Law SYK, Chen LL, Li Y, Qin YR, Guan XY (2012) MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor. Gut 61(1):33–42

    Article  CAS  PubMed  Google Scholar 

  20. Yang HS, Gu J, Wang KK, Zhang W, Xing JL, Chen ZN, Ajani JA, Wu XF (2009) MicroRNA expression signatures in Barrett’s esophagus and esophageal adenocarcinoma. Clin Cancer Res 15(18):5744–5752

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Gottardo F, Liu CG, Ferracin M, Calin GA, Fassan M, Bassi P, Sevignani C, Byrne D, Negrini M, Pagano F, Gomella LG, Croce CM, Baffa R (2007) Micro-RNA profiling in kidney and bladder cancers. Urol Oncol-Semin Ori 25(5):387–392

    Article  CAS  Google Scholar 

  22. Karakatsanis A, Papaconstantinou I, Gazouli M, Lyberopoulou A, Polymeneas G, Voros D (2013) Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance. Mol Carcinog 52(4):297–303

    Article  CAS  PubMed  Google Scholar 

  23. Harris T, Jimenez L, Kawachi N, Fan JB, Chen J, Belbin T, Ramnauth A, Loudig O, Keller CE, Smith R, Prystowsky MB, Schlecht NF, Segall JE, Childs G (2012) Low-level expression of miR-375 correlates with poor outcome and metastasis while altering the invasive properties of head and neck squamous cell carcinomas. Am J Pathol 180(3):917–928

    Article  CAS  PubMed  Google Scholar 

  24. Liu R, Zhang CN, Hu ZB, Li G, Wang C, Yang CH, Huang DZ, Chen X, Zhang HY, Zhuang R, Deng T, Liu H, Yin JJ, Wang SF, Zen K, Ba Y, Zhang CY (2011) A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis. Eur J Cancer 47(5):784–791

    Article  CAS  PubMed  Google Scholar 

  25. Brase JC, Johannes M, Schlomm T, Falth M, Haese A, Steuber T, Beissbarth T, Kuner R, Sultmann H (2011) Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer 128(3):608–616

    Article  CAS  PubMed  Google Scholar 

  26. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M (2008) Circulating microRNAs as stable blood-based markers for cancer detection. P Natl Acad Sci USA 105(30):10513–10518

    Article  CAS  Google Scholar 

  27. Zen K, Zhang CY (2012) Circulating MicroRNAs: a novel class of biomarkers to diagnose and monitor human cancers. Med Res Rev 32(2):326–348

    Article  PubMed  Google Scholar 

  28. Kim YK, Yu J, Han TS, Park SY, Namkoong B, Kim DH, Hur K, Yoo MW, Lee HJ, Yang HK, Kim VN (2009) Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer. Nucleic Acids Res 37(5):1672–1681

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Chen X, Hu Z, Wang W, Ba Y, Ma L, Zhang C, Wang C, Ren Z, Zhao Y, Wu S, Zhuang R, Zhang Y, Hu H, Liu C, Xu L, Wang J, Shen H, Zhang J, Zen K, Zhang CY (2012) Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis. Int J Cancer 130(7):1620–1628

    Article  CAS  PubMed  Google Scholar 

  30. Li X, Zhang Y, Zhang H, Liu X, Gong T, Li M, Sun L, Ji G, Shi Y, Han Z, Han S, Nie Y, Chen X, Zhao Q, Ding J, Wu K, Daiming F (2011) miRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res 9(7):824–833

    Article  CAS  PubMed  Google Scholar 

  31. Li BS, Zhao YL, Guo G, Li W, Zhu ED, Luo X, Mao XH, Zou QM, Yu PW, Zuo QF, Li N, Tang B, Liu KY, Xiao B (2012) Plasma microRNAs, miR-223, miR-21 and miR-218, as novel potential biomarkers for gastric cancer detection. PLoS One 7(7):e41629

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Kurashige J, Watanabe M, Iwatsuki M, Kinoshita K, Saito S, Hiyoshi Y, Kamohara H, Baba Y, Mimori K, Baba H (2012) Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma. Brit J Cancer 106(1):182–188

    Article  CAS  PubMed  Google Scholar 

  33. Tsukamoto Y, Nakada C, Noguchi T, Tanigawa M, Lam TN, Uchida T, Hijiya N, Matsuura K, Fujioka T, Seto M, Moriyama M (2010) MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3 zeta. Cancer Res 70(6):2339–2349

    Article  CAS  PubMed  Google Scholar 

  34. Dai X, Chiang Y, Wang Z, Song Y, Lu C, Gao P, Xu H (2012) Expression levels of microRNA-375 in colorectal carcinoma. Mol Med Rep 5(5):1299–1304

    CAS  PubMed  Google Scholar 

  35. Chang Y, Yan W, He X, Zhang L, Li C, Huang H, Nace G, Geller DA, Lin J, Tsung A (2012) miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions. Gastroenterol 143(1):177–187

    Article  CAS  Google Scholar 

  36. Li J, Li X, Li Y, Yang H, Wang L, Qin Y, Liu H, Fu L, Guan XY (2013) Cell-specific detection of miR-375 downregulation for predicting the prognosis of esophageal squamous cell carcinoma by miRNA in situ hybridization. PLoS One 8(1):e53582

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Zhang HY, Zuo Z, Lu X, Wang L, Wang HY, Zhu ZL (2012) MiR-25 regulates apoptosis by targeting Bim in human ovarian cancer. Oncol Rep 27(2):594–598

    CAS  PubMed  Google Scholar 

  38. Esposito F, Tornincasa M, Pallante P, Federico A, Borbone E, Pierantoni GM, Fusco A (2012) Down-regulation of the miR-25 and miR-30d contributes to the development of anaplastic thyroid carcinoma targeting the polycomb protein EZH2. J Clin Endocrinol Metab 97(5):E710–E718

    Article  CAS  PubMed  Google Scholar 

  39. Zhou K, Yi S, Yu Z, Li Z, Wang Y, Zou D, Qi J, Zhao Y, Qiu L (2012) MicroRNA-223 expression is uniformly down-regulated in B cell lymphoproliferative disorders and is associated with poor survival in patients with chronic lymphocytic leukemia. Leuk Lymphoma 53(6):1155–1161

    Article  CAS  PubMed  Google Scholar 

  40. Kinoshita T, Hanazawa T, Nohata N, Okamoto Y, Seki N (2012) The functional significance of microRNA-375 in human squamous cell carcinoma: aberrant expression and effects on cancer pathways. J Hum Genet 57(9):556–563

    Article  CAS  PubMed  Google Scholar 

  41. Kurashige J, Kamohara H, Watanabe M, Tanaka Y, Kinoshita K, Saito S, Hiyoshi Y, Iwatsuki M, Baba Y, Baba H (2012) Serum microRNA-21 is a novel biomarker in patients with esophageal squamous cell carcinoma. J Surg Oncol 106(2):188–192

    Article  CAS  PubMed  Google Scholar 

  42. Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C, Croce CM (2007) MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA 297(17):1901–1908

    Article  CAS  PubMed  Google Scholar 

  43. Laios A, O’Toole S, Flavin R, Martin C, Kelly L, Ring M, Finn SP, Barrett C, Loda M, Gleeson N, D’Arcy T, McGuinness E, Sheils O, Sheppard B, Leary JO (2008) Potential role of miR-9 and miR-223 in recurrent ovarian cancer. Mol Cancer 7:35

    Article  PubMed Central  PubMed  Google Scholar 

  44. Belair C, Darfeuille F, Staedel C (2009) Helicobacter pylori and gastric cancer: possible role of microRNAs in this intimate relationship. Clin Microbiol Infec 15(9):806–812

    Article  CAS  Google Scholar 

  45. Liu XG, Zhu WY, Huang YY, Ma LN, Zhou SQ, Wang YK, Zeng F, Zhou JH, Zhang YK (2012) High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer. Med Oncol 29(2):618–626

    Article  CAS  PubMed  Google Scholar 

  46. Mathe EA, Nguyen GH, Bowman ED, Zhao YQ, Budhu A, Schetter AJ, Braun R, Reimers M, Kumamoto K, Hughes D, Altorki NK, Casson AG, Liu CG, Wang XW, Yanaihara N, Hagiwara N, Dannenberg AJ, Miyashita M, Croce CM, Harris CC (2009) MicroRNA expression in squamous cell carcinoma and adenocarcinoma of the esophagus: associations with survival. Clin Cancer Res 15(19):6192–6200

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Chin LJ, Slack FJ (2008) A truth serum for cancer—microRNAs have major potential as cancer biomarkers. Cell Res 18(10):983–984

    Article  CAS  PubMed  Google Scholar 

  48. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659

    Article  CAS  PubMed  Google Scholar 

  49. Chen X, Ba Y, Ma LJ, Cai X, Yin Y, Wang KH, Guo JG, Zhang YJ, Chen JN, Guo X, Li QB, Li XY, Wang WJ, Zhang Y, Wang J, Jiang XY, Xiang Y, Xu C, Zheng PP, Zhang JB, Li RQ, Zhang HJ, Shang XB, Gong T, Ning G, Wang J, Zen K, Zhang JF, Zhang CY (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18(10):997–1006

    Article  CAS  PubMed  Google Scholar 

  50. Yao XX, Wang JF, Wang YH, Gao N (2012) Expression of microRNA-223 and its clinicopathologic correlation in diffuse large B-cell lymphoma. Zhonghua Bing Li Xue Za Zhi 41(6):366–370

    CAS  PubMed  Google Scholar 

  51. Stamatopoulos B, Meuleman N, Haibe-Kains B, Saussoy P, Van Den Neste E, Michaux L, Heimann P, Martiat P, Bron D, Lagneaux L (2009) microRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification. Blood 113(21):5237–5245

    Article  CAS  PubMed  Google Scholar 

  52. Zhang X, Yan Z, Zhang J, Gong L, Li W, Cui J, Liu Y, Gao Z, Li J, Shen L, Lu Y (2011) Combination of hsa-miR-375 and hsa-miR-142-5p as a predictor for recurrence risk in gastric cancer patients following surgical resection. Ann Oncol 22(10):2257–2266

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Yuanjirong and Haixian Lu for reading this paper and for their valuable suggestions.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, Zhongshan Hospital, Xiamen University, Fujian, 361004, China

    Chaohui Wu, Minjie Li, Chao Hu & Hongbing Duan

Authors
  1. Chaohui Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Minjie Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chao Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hongbing Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hongbing Duan.

Electronic supplementary material

Below is the link to the electronic supplementary material.

11033_2013_2970_MOESM1_ESM.tif

Fig. S1. Comparison analysis of the change pattern in 20 matched tissue and serum samples. a miR-25. b miR-223. c miR-375. (TIFF 95 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, C., Li, M., Hu, C. et al. Clinical significance of serum miR-223, miR-25 and miR-375 in patients with esophageal squamous cell carcinoma. Mol Biol Rep 41, 1257–1266 (2014). https://doi.org/10.1007/s11033-013-2970-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-013-2970-z

Keywords

Search

Navigation