Tumor Biology

, Volume 35, Issue 10, pp 9613–9617 | Cite as

Clinical significance of the low expression of FER1L4 in gastric cancer patients

  • Zhong Liu
  • Yongfu Shao
  • Lin Tan
  • Huajun Shi
  • Shengcan Chen
  • Junming Guo
Research Article


Long non-coding RNA (lncRNA) is a new class of regulative non-coding RNA, with a length larger than 200 nucleotides. Recent studies found that there are close relations between disregulative lncRNAs and human tumors. However, the clinical significances are largely unknown. In this study, we investigated the lncRNA–Fer-1-like protein 4 (FER1L4) level in gastric cancer tissues and plasma. The FER1L4 level in human tissues and plasma were measured by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Then, the correlations between the tissue or plasma FER1L4 levels and clinicopathological factors were assessed. A receiver operating characteristic (ROC) curve was constructed for differentiating GC patients from controls. Compared to matched adjacent non-tumorous tissues, FER1L4 expression levels in 91.80 % (56/61) of gastric cancer tissues are significantly decreased. The low FER1L4 level were associated with tumor size (p < 0.001), histologic grade (p = 0.001), general classification (p < 0.001), depth of invasion (p < 0.001), lymphatic metastasis (p < 0.001), distant metastasis (p = 0.003), TNM stage (p < 0.001), vessel or nerve invasion (p < 0.001 or p = 0.003), and serum CA72-4 (p < 0.001). The area under the ROC curve (AUC) was up to 0.778 (p < 0.001) and the sensitivity and specificity were 67.2 and 80.3 %, respectively. Also, plasma FER1L4 was detected by qRT-PCR. Our data show that there was no difference of plasma FER1L4 level between healthy person and preoperative gastric cancer patients, with a sharp decline in 63.9 % (53/83) of gastric cancer patients 2 weeks after surgery (p = 0.028). Taken together, FER1L4 might play a crucial role in human gastric cancer and may be a new potential biomarker for clinical prognosis evaluation.


Gastric cancer LncRNA FER1L4 Plasma Tumor marker 



This work was supported by National Natural Science Foundation of China (no. 81171660), the Zhejiang Provincial Natural Science Foundation of China (no. Y14C060003), the Natural Science Foundation of Ningbo (no. 2012A610207), the Ningbo Social Development Research Project (no. 2012C50005), the Scientific Innovation Team Project of Ningbo (no. 2011B82014), the Project of Key Disciplines in Ningbo (nos. XKL11D2127 and XKL11D2128), the Scientific Research Foundation of Graduate School of Ningbo University (no. G14069), and the K. C. Wong Magna Fund in Ningbo University.

Conflicts of interest


Expression microarray data

Expression microarray data accessible at NCBI GEO database, accession GSE478 (Guo, 2013)

Ethics approval

This study was conducted with the approval of The Human Research Ethics Committee of Ningbo University.

Provenance and peer review

Not commissioned; externally peer reviewed.

Supplementary material

13277_2014_2259_MOESM1_ESM.docx (486 kb)
ESM 1 (DOCX 485 kb)


  1. 1.
    Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol. 2011;21:354–61.CrossRefPubMedGoogle Scholar
  2. 2.
    Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S, et al. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature. 2002;420:563–73.CrossRefPubMedGoogle Scholar
  3. 3.
    Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, et al. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science. 2007;316:1484–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Li J, Xuan Z, Liu C. Long non-coding RNAs and complex human diseases. Int J Mol Sci. 2013;14:18790–808.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Clark MB, Mattick JS. Long noncoding RNAs in cell biology. Semin Cell Dev Biol. 2011;22:366–76.CrossRefPubMedGoogle Scholar
  7. 7.
    Hauptman N, Glavac D. Long non-coding RNA in cancer. Int J Mol Sci. 2013;14:4655–69.PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R, Hochberg A, et al. The H19 non-coding RNA is essential for human tumor growth. PLoS One. 2007;2:e845.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Zhou Y, Zhang X, Klibanski A. MEG3 noncoding RNA: a tumor suppressor. J Mol Endocrinol. 2012;48:R45–53.PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Wu HH, Lin WC, Tsai KW. Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers. Expert Rev Mol Med. 2014. doi: 10.1017/erm.2013.16.PubMedCentralPubMedGoogle Scholar
  11. 11.
    Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, et al. Treatment of gastric cancer. World J Gastroenterol. 2014;20:1635–49.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Duraes C, Almeida GM, Seruca R, Oliveira C, Carneiro F. Biomarkers for gastric cancer: prognostic, predictive or targets of therapy? Virchows Arch. 2014;464:367–78.CrossRefPubMedGoogle Scholar
  13. 13.
    Song H, Sun W, Ye G, Ding X, Liu Z, Zhang S, et al. Long non-coding RNA expression profile in human gastric cancer and its clinical significances. J Transl Med. 2013;11:225.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Li CH, Chen Y. Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol. 2013;45:1895–910.CrossRefPubMedGoogle Scholar
  15. 15.
    Tang JY, Lee JC, Chang YT, Hou MF, Huang HW, Liaw CC, et al. Long noncoding RNAs-related diseases, cancers, and drugs. Sci World J. 2013. doi: 10.1155/2013/943539.Google Scholar
  16. 16.
    Sun W, Wu Y, Yu X, Liu Y, Song H, Xia T, et al. Decreased expression of long noncoding RNA AC096655.1-002 in gastric cancer and its clinical significance. Tumour Biol. 2013;34:2697–701.CrossRefPubMedGoogle Scholar
  17. 17.
    Qi P, Xu MD, Ni SJ, Huang D, Wei P, Tan C, et al. Low expression of LOC285194 is associated with poor prognosis in colorectal cancer. J Transl Med. 2013;11:122.PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    He X, Bao W, Li X, Chen Z, Che Q, Wang H, et al. The long non-coding RNA HOTAIR is upregulated in endometrial carcinoma and correlates with poor prognosis. Int J Mol Med. 2014;33:325–32.PubMedGoogle Scholar
  19. 19.
    Weber DG, Johnen G, Casjens S, Bryk O, Pesch B, Jöckel KH, et al. Evaluation of long noncoding RNA MALAT1 as a candidate blood-based biomarker for the diagnosis of non-small cell lung cancer. BMC Res Notes. 2013;6:518.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Wang W, Li YF, Sun XW, Chen YB, Li W, Xu DZ, et al. Prognosis of 980 patients with gastric cancer after surgical resection. Chin J Cancer. 2010;29:923–30.CrossRefPubMedGoogle Scholar
  21. 21.
    Selcukbiricik F, Tural D, Buyukunal E, Serdengeçti S. Perineural invasion independent prognostic factors in patients with gastric cancer undergoing curative resection. Asian Pac J Cancer Prev. 2012;13:3149–52.CrossRefPubMedGoogle Scholar
  22. 22.
    Saito H, Osaki T, Murakami D, Sakamoto T, Kanaji S, Oro S, et al. Macroscopic tumor size as a simple prognostic indicator in patients with gastric cancer. AmJ Surg. 2006;192:296–300.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of General SurgeryThe Affiliated Hospital of Ningbo University School of MedicineNingboChina
  2. 2.Department of Biochemistry and Molecular Biology, and Zhejiang Provincial Key Laboratory of PathophysiologyNingbo University School of MedicineNingboChina

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