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High microRNA-28-5p expression in colorectal adenocarcinoma predicts short-term relapse of node-negative patients and poor overall survival of patients with non-metastatic disease

  • Panagiotis Tsiakanikas , Christos K. Kontos , Dimitrios Kerimis , Iordanis N. Papadopoulos and Andreas Scorilas EMAIL logo
Published/Copyright: April 24, 2018
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 56 Issue 6

Abstract

Background:

MicroRNAs (miRNAs) may function either as oncogenes or tumor suppressors and are heavily involved in the initiation and progression of cancer, and in metastasis of tumor cells. MicroRNA-28-5p (miR-28-5p) targets several cancer-related genes and is hence involved in cell proliferation, migration, invasion and epithelial-mesenchymal transition. In this study, we investigated the potential diagnostic and prognostic significance of miR-28-5p expression in colorectal adenocarcinoma, the most frequent type of colorectal cancer (CRC).

Methods:

Therefore, we isolated total RNA from 182 colorectal adenocarcinoma specimens and 86 paired non-cancerous colorectal mucosae. After polyadenylation of 2 μg total RNA and its reverse transcription using an oligo-dT-adapter primer, we quantified miR-28-5p levels using an in-house-developed reverse-transcription real-time quantitative polymerase chain reaction (RT-qPCR) method, based on the SYBR Green chemistry.

Results:

Comparison of miR-28-5p levels among 86 pairs of colorectal tumors and their adjacent non-cancerous mucosae uncovered the downregulation of miR-28-5p expression in the majority of malignant colorectal tumors. More importantly, high miR-28-5p expression predicts poor disease-free survival (DFS) and overall survival (OS) of colorectal adenocarcinoma patients. Multivariate Cox regression analysis revealed that miR-28-5p overexpression is a significant predictor of poor prognosis in colorectal adenocarcinoma, independent of tumor size, histological grade, TNM staging, radiotherapy and chemotherapy. Interestingly, strong miR-28-5p expression retains its predictive potential regarding relapse among patients with negative regional lymph nodes, and predicts poor OS in patients diagnosed with non-metastatic colorectal adenocarcinoma.

Conclusions:

High miR-28-5p expression predicts poor DFS and OS of colorectal adenocarcinoma patients, independently of clinicopathological prognosticators and standard patient treatment, including radiotherapy and chemotherapy.

Keywords: colon cancer; microRNA-28 (miRNA-28); molecular tumor markers; prognosis; prognostic biomarkers; real-time quantitative real-time PCR (RT-qPCR)

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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. Smith RA, Cokkinides V, Brooks D, Saslow D, Brawley OW. Cancer screening in the United States, 2010: a review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin 2010;60:99–119.10.3322/caac.20063Search in Google Scholar

2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893–917.10.1002/ijc.25516Search in Google Scholar

3. Schoen RE. Families at risk for colorectal cancer: risk assessment and genetic testing. J Clin Gastroenterol 2000;31:114–20.10.1097/00004836-200009000-00005Search in Google Scholar

4. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990;61:759–67.10.1016/0092-8674(90)90186-ISearch in Google Scholar

5. Steinberg SM, Barkin JS, Kaplan RS, Stablein DM. Prognostic indicators of colon tumors. The gastrointestinal tumor study group experience. Cancer 1986;57:1866–70.10.1002/1097-0142(19860501)57:9<1866::AID-CNCR2820570928>3.0.CO;2-TSearch in Google Scholar

6. Compton CC, Greene FL. The staging of colorectal cancer: 2004 and beyond. CA Cancer J Clin 2004;54:295–308.10.3322/canjclin.54.6.295Search in Google Scholar

7. Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science 2001;294:862–4.10.1126/science.1065329Search in Google Scholar

8. Esquela-Kerscher A, Slack FJ. Oncomirs – microRNAs with a role in cancer. Nat Rev Cancer 2006;6:259–69.10.1038/nrc1840Search in Google Scholar

9. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer 2006;6:857–66.10.1038/nrc1997Search in Google Scholar

10. Luo X, Burwinkel B, Tao S, Brenner H. MicroRNA signatures: novel biomarker for colorectal cancer? Cancer Epidemiol Biomarkers Prev 2011;20:1272–86.10.1158/1055-9965.EPI-11-0035Search in Google Scholar

11. Zhao J, Zhang Y, Zhao G. Emerging role of microRNA-21 in colorectal cancer. Cancer Biomark 2015;15:219–26.10.3233/CBM-150468Search in Google Scholar PubMed

12. Ferraro A, Kontos CK, Boni T, Bantounas I, Siakouli D, Kosmidou V, et al. Epigenetic regulation of miR-21 in colorectal cancer: ITGB4 as a novel miR-21 target and a three-gene network (miR-21-ITGBeta4-PDCD4) as predictor of metastatic tumor potential. Epigenetics 2014;9:129–41.10.4161/epi.26842Search in Google Scholar PubMed PubMed Central

13. Su J, Liang H, Yao W, Wang N, Zhang S, Yan X, et al. MiR-143 and MiR-145 regulate IGF1R to suppress cell proliferation in colorectal cancer. PLoS One 2014;9:e114420.10.1371/journal.pone.0114420Search in Google Scholar PubMed PubMed Central

14. Almeida MI, Nicoloso MS, Zeng L, Ivan C, Spizzo R, Gafa R, et al. Strand-specific miR-28-5p and miR-28-3p have distinct effects in colorectal cancer cells. Gastroenterology 2012;142:886–96.10.1053/j.gastro.2011.12.047Search in Google Scholar PubMed PubMed Central

15. Xu J, Jiang N, Shi H, Zhao S, Yao S, Shen H. miR-28-5p promotes the development and progression of ovarian cancer through inhibition of N4BP1. Int J Oncol 2017;50:1383–91.10.3892/ijo.2017.3915Search in Google Scholar PubMed

16. Palakurthy RK, Wajapeyee N, Santra MK, Gazin C, Lin L, Gobeil S, et al. Epigenetic silencing of the RASSF1A tumor suppressor gene through HOXB3-mediated induction of DNMT3B expression. Mol Cell 2009;36:219–30.10.1016/j.molcel.2009.10.009Search in Google Scholar PubMed PubMed Central

17. Shi X, Teng F. Down-regulated miR-28-5p in human hepatocellular carcinoma correlated with tumor proliferation and migration by targeting insulin-like growth factor-1 (IGF-1). Mole Cell Biochem 2015;408:283–93.10.1007/s11010-015-2506-zSearch in Google Scholar PubMed

18. Hell MP, Thoma CR, Fankhauser N, Christinat Y, Weber TC, Krek W. miR-28-5p promotes chromosomal instability in VHL-associated cancers by inhibiting Mad2 translation. Cancer Res 2014;74:2432–43.10.1158/0008-5472.CAN-13-2041Search in Google Scholar PubMed

19. Wang C, Wu C, Yang Q, Ding M, Zhong J, Zhang CY, et al. miR-28-5p acts as a tumor suppressor in renal cell carcinoma for multiple antitumor effects by targeting RAP1B. Oncotarget 2016;7:73888–902.10.18632/oncotarget.12516Search in Google Scholar PubMed PubMed Central

20. Zhu RY, Zhang D, Zou HD, Zuo XS, Zhou QS, Huang H. MiR-28 inhibits cardiomyocyte survival through suppressing PDK1/Akt/mTOR signaling. In vitro Cellular Develop Biol. Animal 2016;52:1020–5.Search in Google Scholar

21. Nagtegaal ID, Quirke P, Schmoll HJ. Has the new TNM classification for colorectal cancer improved care? Nature reviews. Clin Oncol 2011;9:119–23.Search in Google Scholar

22. Diamantopoulos MA, Kontos CK, Kerimis D, Papadopoulos IN, Scorilas A. Upregulated miR-16 expression is an independent indicator of relapse and poor overall survival of colorectal adenocarcinoma patients. Clin Chem Lab Med 2017;55:737–47.10.1515/cclm-2016-0756Search in Google Scholar PubMed

23. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 2002;3:research0034.1–11.10.1186/gb-2002-3-7-research0034Search in Google Scholar PubMed PubMed Central

24. Christodoulou S, Alexopoulou DK, Kontos CK, Scorilas A, Papadopoulos IN. Kallikrein-related peptidase-6 (KLK6) mRNA expression is an independent prognostic tissue biomarker of poor disease-free and overall survival in colorectal adenocarcinoma. Tumour Biol 2014;35:4673–85.10.1007/s13277-014-1612-ySearch in Google Scholar PubMed

25. Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 2004;10:7252–9.10.1158/1078-0432.CCR-04-0713Search in Google Scholar PubMed

26. Jemal A, Ward EM, Johnson CJ, Cronin KA, Ma J, Ryerson B, et al. Annual report to the Nation on the status of cancer, 1975–2014, featuring survival. J Natl Cancer Inst 2017;109. doi: 10.1093/jnci/djx030.10.1093/jnci/djx030Search in Google Scholar PubMed PubMed Central

27. Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med 2015;21:1350–6.10.1038/nm.3967Search in Google Scholar PubMed PubMed Central

28. Mlcochova J, Faltejskova P, Nemecek R, Svoboda M, Slaby O. MicroRNAs targeting EGFR signalling pathway in colorectal cancer. J Cancer Res Clin Oncol 2013;139:1615–24.10.1007/s00432-013-1470-9Search in Google Scholar PubMed

29. Fan C, Lin Y, Mao Y, Huang Z, Liu AY, Ma H, et al. MicroRNA-543 suppresses colorectal cancer growth and metastasis by targeting KRAS, MTA1 and HMGA2. Oncotarget 2016;7:21825–39.10.18632/oncotarget.7989Search in Google Scholar PubMed PubMed Central

30. Yamada N, Noguchi S, Mori T, Naoe T, Maruo K, Akao Y. Tumor-suppressive microRNA-145 targets catenin delta-1 to regulate Wnt/beta-catenin signaling in human colon cancer cells. Cancer Lett 2013;335:332–42.10.1016/j.canlet.2013.02.060Search in Google Scholar PubMed

31. Nagel R, le Sage C, Diosdado B, van der Waal M, Oude Vrielink JA, Bolijn A, et al. Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer. Cancer Res 2008;68:5795–802.10.1158/0008-5472.CAN-08-0951Search in Google Scholar PubMed

32. Ma Y, Li W, Wang H. Roles of miRNA in the initiation and development of colorectal carcinoma. Curr Pharm Des 2013;19:1253–61.Search in Google Scholar

33. Ma Q, Wang X, Li Z, Li B, Ma F, Peng L, et al. microRNA-16 represses colorectal cancer cell growth in vitro by regulating the p53/survivin signaling pathway. Oncol Rep 2013;29:1652–8.10.3892/or.2013.2262Search in Google Scholar PubMed

34. Yu Y, Kanwar SS, Patel BB, Oh PS, Nautiyal J, Sarkar FH, et al. MicroRNA-21 induces stemness by downregulating transforming growth factor beta receptor 2 (TGFbetaR2) in colon cancer cells. Carcinogenesis 2012;33:68–76.10.1093/carcin/bgr246Search in Google Scholar PubMed PubMed Central

35. Schetter AJ, Harris CC. Alterations of microRNAs contribute to colon carcinogenesis. Semin Oncol 2011;38:734–42.10.1053/j.seminoncol.2011.08.009Search in Google Scholar PubMed PubMed Central

36. Menendez P, Villarejo P, Padilla D, Menendez JM, Rodriguez-Montes JA. Implications of the histological determination of microRNAs in the screening, diagnosis and prognosis of colorectal cancer. J Surg Oncol 2013;108:70–3.10.1002/jso.23344Search in Google Scholar PubMed

37. Madhavan D, Cuk K, Burwinkel B, Yang R. Cancer diagnosis and prognosis decoded by blood-based circulating microRNA signatures. Front Genet 2013;4:116.10.3389/fgene.2013.00116Search in Google Scholar PubMed PubMed Central

38. Bartley AN, Yao H, Barkoh BA, Ivan C, Mishra BM, Rashid A, et al. Complex patterns of altered MicroRNA expression during the adenoma-adenocarcinoma sequence for microsatellite-stable colorectal cancer. Clin Cancer Res 2011;17:7283–93.10.1158/1078-0432.CCR-11-1452Search in Google Scholar PubMed PubMed Central

39. Wu CW, Ng SS, Dong YJ, Ng SC, Leung WW, Lee CW, et al. Detection of miR-92a and miR-21 in stool samples as potential screening biomarkers for colorectal cancer and polyps. Gut 2012;61:739–45.10.1136/gut.2011.239236Search in Google Scholar PubMed

40. Xiao YF, Yong X, Fan YH, Lu MH, Yang SM, Hu CJ. microRNA detection in feces, sputum, pleural effusion and urine: novel tools for cancer screening [Review]. Oncol Rep 2013;30:535–44.10.3892/or.2013.2525Search in Google Scholar PubMed

41. Kalimutho M, Del Vecchio Blanco G, Di Cecilia S, Sileri P, Cretella M, Pallone F, et al. Differential expression of miR-144* as a novel fecal-based diagnostic marker for colorectal cancer. J Gastroenterol 2011;46:1391–402.10.1007/s00535-011-0456-0Search in Google Scholar PubMed

42. Rapti SM, Kontos CK, Papadopoulos IN, Scorilas A. High miR-96 levels in colorectal adenocarcinoma predict poor prognosis, particularly in patients without distant metastasis at the time of initial diagnosis. Tumour Biol 2016;37:11815–24.10.1007/s13277-016-5023-0Search in Google Scholar PubMed

43. Rapti SM, Kontos CK, Papadopoulos IN, Scorilas A. Enhanced miR-182 transcription is a predictor of poor overall survival in colorectal adenocarcinoma patients. Clin Chem Lab Med 2014;52:1217–27.10.1515/cclm-2013-0950Search in Google Scholar PubMed

44. Adamopoulos PG, Kontos CK, Rapti SM, Papadopoulos IN, Scorilas A. miR-224 overexpression is a strong and independent prognosticator of short-term relapse and poor overall survival in colorectal adenocarcinoma. Int J Oncol 2015;46:849–59.10.3892/ijo.2014.2775Search in Google Scholar PubMed

45. Kerimis D, Kontos CK, Christodoulou S, Papadopoulos IN, Scorilas A. Elevated expression of miR-24-3p is a potentially adverse prognostic factor in colorectal adenocarcinoma. Clin Biochem 2017;50:285–92.10.1016/j.clinbiochem.2016.11.034Search in Google Scholar PubMed

46. Kontos CK, Tsiakanikas P, Avgeris M, Papadopoulos IN, Scorilas A. miR-15a-5p, A novel prognostic biomarker, predicting recurrent colorectal adenocarcinoma. Mol Diagn Ther 2017;21:453–64.10.1007/s40291-017-0270-3Search in Google Scholar PubMed

47. Rapti SM, Kontos CK, Christodoulou S, Papadopoulos IN, Scorilas A. miR-34a overexpression predicts poor prognostic outcome in colorectal adenocarcinoma, independently of clinicopathological factors with established prognostic value. Clin Biochem 2017;50:918–24.10.1016/j.clinbiochem.2017.06.004Search in Google Scholar PubMed

48. Wang C, Hu J, Lu M, Gu H, Zhou X, Chen X, et al. A panel of five serum miRNAs as a potential diagnostic tool for early-stage renal cell carcinoma. Sci Rep 2015;5:7610.10.1038/srep07610Search in Google Scholar PubMed PubMed Central

49. Zhou SL, Hu ZQ, Zhou ZJ, Dai Z, Wang Z, Cao Y, et al. miR-28-5p-IL-34-macrophage feedback loop modulates hepatocellular carcinoma metastasis. Hepatology 2016;63:1560–75.10.1002/hep.28445Search in Google Scholar PubMed

50. Lim EL, Trinh DL, Scott DW, Chu A, Krzywinski M, Zhao Y, et al. Comprehensive miRNA sequence analysis reveals survival differences in diffuse large B-cell lymphoma patients. Genome Biol 2015;16:18.10.1186/s13059-014-0568-ySearch in Google Scholar PubMed PubMed Central

51. Schneider NI, Langner C. Prognostic stratification of colorectal cancer patients: current perspectives. Cancer Manag Res 2014;6:291–300.10.2147/CMAR.S38827Search in Google Scholar PubMed PubMed Central

52. Du WW, Fang L, Li M, Yang X, Liang Y, Peng C, et al. MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling. J Cell Sci 2013;126:1440–53.10.1242/jcs.118299Search in Google Scholar PubMed

53. Tian R, Liu T, Qiao L, Gao M, Li J. Decreased serum microRNA-206 level predicts unfavorable prognosis in patients with melanoma. Int J Clin Exp Pathol 2015;8:3097–103.Search in Google Scholar

Supplemental Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2017-0430).

Received: 2017-5-15
Accepted: 2017-12-17
Published Online: 2018-4-24
Published in Print: 2018-5-24

©2018 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2017-0430
Keywords for this article
colon cancer; microRNA-28 (miRNA-28); molecular tumor markers; prognosis; prognostic biomarkers; real-time quantitative real-time PCR (RT-qPCR)

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Developments in laboratory testing for autoimmune diseases
  4. Reviews
  5. Cerebrospinal fluid microRNAs as diagnostic biomarkers in brain tumors
  6. HCV core antigen comes of age: a new opportunity for the diagnosis of hepatitis C virus infection
  7. Mini Reviews
  8. Insulin autoimmune syndrome (Hirata’s disease) in an Italian patient: a case report and review of the literature
  9. The natural history of autoimmune Addison’s disease with a non-classical presentation: a case report and review of literature
  10. Opinion Paper
  11. Quality and future of clinical laboratories: the Vico’s whole cyclical theory of the recurring cycles
  12. General Clinical Chemistry and Laboratory Medicine
  13. Screening for connective tissue disease-associated antibodies by automated immunoassay
  14. Analysis of anti-ganglioside antibodies by a line immunoassay in patients with chronic-inflammatory demyelinating polyneuropathies (CIDP)
  15. Detection of autoantibodies to the p200-epitope of SSA/Ro52 antigen. A comparison of two laboratory assays
  16. A new ELISA for autoantibodies to steroid 21-hydroxylase
  17. Antibodies to phosphatidylserine/prothrombin (aPS/PT) enhanced the diagnostic performance in Chinese patients with antiphospholipid syndrome
  18. Borderline positive antineutrophil cytoplasmic antibodies (ANCA)-PR3/MPO detection in a large cohort tertiary center: lessons learnt from a real-life experience
  19. Reference Values and Biological Variations
  20. Short- and medium-term biological variation estimates of red blood cell and reticulocyte parameters in healthy subjects
  21. Pediatric reference intervals for 1,25-dihydroxyvitamin D using the DiaSorin LIAISON XL assay in the healthy CALIPER cohort
  22. Reference intervals for biochemical, haemostatic and haematological parameters in healthy Chinese women during early and late pregnancy
  23. Cancer Diagnostics
  24. Use of circulating tumor cells in prospective clinical trials for NSCLC patients – standardization of the pre-analytical conditions
  25. High microRNA-28-5p expression in colorectal adenocarcinoma predicts short-term relapse of node-negative patients and poor overall survival of patients with non-metastatic disease
  26. Infectious Diseases
  27. Diagnosis of acute pediatric appendicitis from children with inflammatory diseases by combination of metabolic markers and inflammatory response variables
  28. Letters to the Editor
  29. Repeat requesting on hemolysed plasma potassium requests
  30. A case report of insulin autoimmune syndrome in a Central European individual
  31. Traceability of alkaline phosphatase measurement may also vary considerably using the same analytical system: the case of Abbott Architect
  32. Abiraterone acetate: a potential source of interference in testosterone assays
  33. Falsely elevated plasma testosterone concentrations in neonates: importance of LC-MS/MS measurements
  34. Rational approach to the primary evaluation of thyroid disease in paediatrics. Full thyroid profile vs. thyroid-stimulating hormone and free thyroxine only
  35. Diagnostic performance of the N-terminal pro-brain natriuretic peptide to detect an increased left atrial pressure in patients with persistent atrial fibrillation
  36. Is the DNA of placental origin packaged in exosomes isolated from plasma and serum of pregnant women?
  37. Gamma heavy chain disease evolving during the progression of chronic lymphocytic leukemia
  38. Congress Abstracts
  39. ISMD2018 Twelfth International Symposium on Molecular Diagnostics
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