Abstract
Background
Long non-coding RNAs (lncRNAs) have been reported to play a key role in gastric cancer (GC) tumorigenesis. However, the clinical application value of serum lncRNAs in GC has remained largely unknown. We investigated the role of a novel lncRNA named CTC-497E21.4 in the diagnosis and the prognosis of GC.
Methods
We focused on evaluation of lncRNA CTC-497E21.4 by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR). The study involved following aspects: (1) confirmation of the higher lncRNA CTC-497E21.4 expression in different types of GC specimens than corresponding controls; (2) evaluation of monitoring tumor dynamics by the serum lncRNA CTC-497E21.4 assay; (3) evaluation of the prognostic value of lncRNA CTC-497E21.4 assay in GC.
Results
(1) The method of RTFQ-PCR detection of lncRNA CTC-497E21.4 was evaluated to have high sensitivity and specificity. (2) The expression levels of lncRNA CTC-497E21.4 were higher in GC patients compared with corresponding controls (p<0.001), and the combination of serum lncRNA CTC-497E21.4, CEA and CA19-9 could improve diagnostic sensitivity (96.36%). (3) The serum lncRNA CTC-497E21.4 expression levels were lower in postoperative samples than preoperative samples (p=0.0021) and survival curves downloaded from TCGA showed high lncRNA CTC-497E21.4 levels were associated with poor OS of GC (p=0.0351).
Conclusions
lncRNA CTC-497E21.4 may be a potential biomarker for the diagnosis and the prognosis of GC.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This study was supported by the National Nature Science Foundation (Grant numbers 81201349, 81000775); Young medical key talents in Jiangsu province (Grant numbers QNRC 2016686, 2016687); Frontier and key technical innovation projects of Nantong (Grant number MS22015049); Nantong Science and Technology Plan Project (MS12017008-3).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. Lancet 2016;388:2654–64.10.1016/S0140-6736(16)30354-3Search in Google Scholar
2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87–108.10.3322/caac.21262Search in Google Scholar PubMed
3. Kanda M, Kodera Y. Recent advances in the molecular diagnostics of gastric cancer. World J Gastroenterol 2015;21:9838–52.10.3748/wjg.v21.i34.9838Search in Google Scholar PubMed PubMed Central
4. Kanda M, Kodera Y. Molecular mechanisms of peritoneal dissemination in gastric cancer. World J Gastroenterol 2016;22:6829–40.10.3748/wjg.v22.i30.6829Search in Google Scholar PubMed PubMed Central
5. Sisik A, Kaya M, Bas G, Basak F, Alimoglu O. CEA and CA 19-9 are still valuable markers for the prognosis of colorectal and gastric cancer patients. Asian Pac J Cancer Prev 2013;14:4289–94.10.7314/APJCP.2013.14.7.4289Search in Google Scholar PubMed
6. Liu X, Cai H, Wang Y. Prognostic significance of tumour markers in Chinese patients with gastric cancer. ANZ J Surg 2014;84:448–53.10.1111/j.1445-2197.2012.06287.xSearch in Google Scholar PubMed
7. Jing JX, Wang Y, Xu XQ, Sun T, Tian BG, Du LL, et al. Tumor markers for diagnosis, monitoring of recurrence and prognosis in patients with upper gastrointestinal tract cancer. Asian Pac J Cancer Prev 2014;15:10267–72.10.7314/APJCP.2014.15.23.10267Search in Google Scholar
8. Zhou Y-C, Zhao H-J, Shen L-Z. Preoperative serum CEA and CA19-9 in gastric cancer – a single tertiary hospital study of 1075 cases. Asian Pac J Cancer Prev 2015;16:2685–91.10.7314/APJCP.2015.16.7.2685Search in Google Scholar
9. Wu HH, Lin WC, Tsai KW. Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers. Expert Rev Mol Med 2014;16:e1.10.1017/erm.2013.16Search in Google Scholar PubMed PubMed Central
10. Guttman M, Rinn JL. Modular regulatory principles of large non-coding RNAs. Nature 2012;482:339–46.10.1038/nature10887Search in Google Scholar PubMed PubMed Central
11. Shigeyasu K, Toden S, Zumwalt TJ, Okugawa Y, Goel A. Emerging role of MicroRNAs as liquid biopsy biomarkers in gastrointestinal cancers. Clin Cancer Res 2017;23:2391–9.10.1158/1078-0432.CCR-16-1676Search in Google Scholar PubMed PubMed Central
12. Zhou X, Yin C, Dang Y, Ye F, Zhang G. Identification of the long non-coding RNA H19 in plasma as a novel biomarker for diagnosis of gastric cancer. Sci Rep 2015;5:11516.10.1038/srep11516Search in Google Scholar PubMed PubMed Central
13. Wang HM, Lu JH, Chen WY, Gu AQ. Upregulated lncRNA-UCA1 contributes to progression of lung cancer and is closely related to clinical diagnosis as a predictive biomarker in plasma. Int J Clin Exp Med 2015;8:11824–30.Search in Google Scholar
14. Seitz AK, Christensen LL, Christensen E, Faarkrog K, Ostenfeld MS, Hedegaard J, et al. Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer. Sci Rep 2017;7:395.10.1038/s41598-017-00327-0Search in Google Scholar PubMed PubMed Central
15. Pan Y, Chen H, Shen X, Wang X, Ju S, Lu M, et al. Serum level of long noncoding RNA H19 as a diagnostic biomarker of multiple myeloma. Clin Chim Acta 2018;480:199–205.10.1016/j.cca.2018.02.019Search in Google Scholar PubMed
16. Chen F, Shen J, Wang J, Cai P, Huang Y. Clinical analysis of four serum tumor markers in 458 patients with ovarian tumors: diagnostic value of the combined use of HE4, CA125, CA19-9, and CEA in ovarian tumors. Cancer Manag Res 2018;10:1313–8.10.2147/CMAR.S155693Search in Google Scholar PubMed PubMed Central
17. He CZ, Zhang KH, Li Q, Liu XH, Hong Y, Lv NH. Combined use of AFP, CEA, CA125 and CAl9-9 improves the sensitivity for the diagnosis of gastric cancer. BMC Gastroenterol 2013;13:87.10.1186/1471-230X-13-87Search in Google Scholar PubMed PubMed Central
18. Tong YS, Wang XW, Zhou XL, Liu ZH, Yang TX, Shi WH, et al. Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma. Mol Cancer 2015;14:3.10.1186/1476-4598-14-3Search in Google Scholar PubMed PubMed Central
19. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359–86.10.1002/ijc.29210Search in Google Scholar PubMed
20. Zong W, Ju S, Jing R, Cui M. Long non-coding RNA-mediated regulation of signaling pathways in gastric cancer. Clin Chem Lab Med 2018;56:1828–37.10.1515/cclm-2017-1139Search in Google Scholar PubMed
21. Sawaki K, Kanda M, Kodera Y. Review of recent efforts to discover biomarkers for early detection, monitoring, prognosis, and prediction of treatment responses of patients with gastric cancer. Expert Rev Gastroenterol Hepatol 2018;12:657–70.10.1080/17474124.2018.1489233Search in Google Scholar PubMed
22. Li TT, Liu H, Yu J, Shi GY, Zhao LY, Li GX. Prognostic and predictive blood biomarkers in gastric cancer and the potential application of circulating tumor cells. World J Gastroenterol 2018;24:2236–46.10.3748/wjg.v24.i21.2236Search in Google Scholar PubMed PubMed Central
23. Tantai J, Hu D, Yang Y, Geng J. Combined identification of long non-coding RNA XIST and HIF1A-AS1 in serum as an effective screening for non-small cell lung cancer. Int J Clin Exp Pathol 2015;8:7887–95.Search in Google Scholar
24. Shao T, Huang J, Zheng Z, Wu Q, Liu T, Lv X. SCCA, TSGF, and the Long non-coding RNA AC007271.3 are effective biomarkers for diagnosing oral squamous cell carcinoma. Cell Physiol Biochem 2018;47:26–38.10.1159/000489741Search in Google Scholar PubMed
25. Zhao W, Song M, Zhang J, Kuerban M, Wang H. Combined identification of long non-coding RNA CCAT1 and HOTAIR in serum as an effective screening for colorectal carcinoma. Int J Clin Exp Pathol 2015;8:14131–40.Search in Google Scholar
26. Zhao R, Zhang Y, Zhang X, Yang Y, Zheng X, Li X, et al. Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer. Mol Cancer 2018;17:68.10.1186/s12943-018-0817-xSearch in Google Scholar PubMed PubMed Central
27. He W, Zhong G, Jiang N, Wang B, Fan X, Chen C, et al. Long noncoding RNA BLACAT2 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis. J Clin Invest 2018;128:861–75.10.1172/JCI96218Search in Google Scholar PubMed PubMed Central
28. Guo E, Liang C, He X, Song G, Liu H, Lv Z, et al. Long noncoding RNA LINC00958 accelerates gliomagenesis through regulating miR-203/CDK2. DNA Cell Biol 2018;37:465–72.10.1089/dna.2018.4163Search in Google Scholar PubMed
29. Chen XZ, Zhang WK, Yang K, Wang LL, Liu J, Wang L, et al. Correlation between serum CA724 and gastric cancer: multiple analyses based on Chinese population. Mol Biol Rep 2012;39:9031–9.10.1007/s11033-012-1774-xSearch in Google Scholar PubMed
30. Yang AP, Liu J, Lei HY, Zhang QW, Zhao L, Yang GH. CA72-4 combined with CEA, CA125 and CAl9-9 improves the sensitivity for the early diagnosis of gastric cancer. Clin Chim Acta 2014;437:183–6.10.1016/j.cca.2014.07.034Search in Google Scholar PubMed
31. Ma B, Li M, Zhang L, Huang M, Lei JB, Fu GH, et al. Upregulation of long non-coding RNA TUG1 correlates with poor prognosis and disease status in osteosarcoma. Tumour Biol 2016;37:4445–55.10.1007/s13277-015-4301-6Search in Google Scholar PubMed
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