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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 6-7/2017

01-10-2017 | Research Paper

MicroRNAs and their role for T stage determination and lymph node metastasis in early colon carcinoma

Authors: Melanie Rammer, Gerald Webersinke, Sophie Haitchi-Petnehazy, Eva Maier, Hubert Hackl, Pornpimol Charoentong, Theodora Malli, Maria Steinmair, Andreas L. Petzer, Holger Rumpold

Published in: Clinical & Experimental Metastasis | Issue 6-7/2017

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Abstract

Worldwide, colon cancer is among the most common cancer entities. Understanding the molecular background is the key to enable accurate stage determination, which is crucial to assess optimal therapy options. The search for preoperative biomarkers is ongoing. In recent years, several studies have proposed a diagnostic and prognostic role for miRNAs in cancer. Aim of this study was to evaluate miRNA expression patterns correlating with tumor stage, especially lymph node metastasis, in primary colon carcinoma tissue. Screening was accomplished using GeneChip® miRNA v3.0 arrays (Thermo Fisher Scientific, Waltham, MA, USA) and validated via TaqMan® qPCR assays (Thermo Fisher Scientific, Waltham, MA, USA) to investigate miRNA expressions in 168 FFPE and 83 fresh frozen colon carcinoma samples. Regarding lymph node status, analyses displayed no significantly differential miRNA expression. Interestingly, divergent expression of miR-18a-5p, miR-20a-5p, miR-21-5p, miR-152-3p and miR-1973 was detected in stage pT1. Although miRNAs might not represent reliable biomarkers regarding lymph node metastasis status, they could support risk assessment in stage T1 tumors.
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Literature
1.
Torre LA et al (2015) Global cancer statistics, 2012. Cancer J Clin 65(2):87–108CrossRef
2.
Kawada K, Taketo MM (2011) Significance and mechanism of lymph node metastasis in cancer progression. Cancer Res 71(4):1214–1218CrossRefPubMed
3.
Sobin LH, Gospodarowicz MK, Wittekind C (2009) TNM classification of malignant tumours, 7th edn. Wiley-Blackwell in affiliation with the International Union against Cancer (UICC), Chichester
4.
5.
Biagi JJ et al (2011) Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA 305(22):2335–2342CrossRefPubMed
6.
Kaufmann M et al (2006) Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol 24(12):1940–1949CrossRefPubMed
7.
Gillen S et al (2010) Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 7(4):e1000267CrossRefPubMedPubMedCentral
8.
Sauer R et al (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 30(16):1926–1933CrossRefPubMed
9.
Reim D et al (2015) Clinical research of neoadjuvant chemotherapy for gastric cancer—current and future concepts. Transl Gastrointest Cancer 4(2):131–140
10.
Hendren S et al (2010) Surgical complications are associated with omission of chemotherapy for stage III colorectal cancer. Dis Colon Rectum 53(12):1587–1593CrossRefPubMed
11.
Arredondo J et al (2017) Mid-term oncologic outcome of a novel approach for locally advanced colon cancer with neoadjuvant chemotherapy and surgery. Clin Transl Oncol 19(3):379–385CrossRefPubMed
12.
Karoui M et al (2015) Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial–the PRODIGE 22–ECKINOXE trial. BMC Cancer 15:511CrossRefPubMedPubMedCentral
13.
Liu F et al (2016) CapOX as neoadjuvant chemotherapy for locally advanced operable colon cancer patients: a prospective single-arm phase II trial. Chin J Cancer Res 28(6):589–597CrossRefPubMedPubMedCentral
14.
15.
16.
17.
Fidler IJ, Kripke ML (1977) Metastasis results from preexisting variant cells within a malignant tumor. Science 197(4306):893–895CrossRefPubMed
18.
Calin GA et al (2002) Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 99(24):15524–15529CrossRefPubMedPubMedCentral
19.
Ma Y et al (2012) Candidate microRNA biomarkers in human colorectal cancer: systematic review profiling studies and experimental validation. Int J Cancer 130(9):2077–2087CrossRefPubMed
20.
Faltejskova P et al (2012) Identification and functional screening of microRNAs highly deregulated in colorectal cancer. J Cell Mol Med 16(11):2655–2666CrossRefPubMedPubMedCentral
21.
Zhang JX et al (2013) Prognostic and predictive value of a microRNA signature in stage II colon cancer: a microRNA expression analysis. Lancet Oncol 14(13):1295–1306CrossRefPubMed
22.
23.
Fischer AH et al. (2008) Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc 2008:pdb prot4986
24.
25.
Smyth GK (2005) limma: linear models for microarray data. In: Gentleman R et al (eds) Bioinformatics and computational biology solutions using R and bioconductor. Statistics for biology and health. Springer, New York, pp 397–420CrossRef
26.
Gautier L et al (2004) affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20(3):307–315CrossRefPubMed
27.
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408CrossRefPubMed
28.
The Cancer Genome Atlas Network (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487(7407):330–337CrossRefPubMedCentral
29.
Kritsanasakul A et al (2012) Impact of lymph node retrieval on surgical outcomes in colorectal cancers. J Surg Oncol 106(3):238–242CrossRefPubMed
30.
31.
32.
Slaby O et al (2007) Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Int Soc Cell 72(5–6):397–402
33.
Xiong B et al (2013) MiR-21 regulates biological behavior through the PTEN/PI-3 K/Akt signaling pathway in human colorectal cancer cells. Int J Oncol 42(1):219–228CrossRefPubMed
34.
Huang ZM et al (2009) MicroRNA expression profile in non-cancerous colonic tissue associated with lymph node metastasis of colon cancer. J Dig Dis 10(3):188–194CrossRefPubMed
35.
Wang X et al (2012) Downregulation of miR-195 correlates with lymph node metastasis and poor prognosis in colorectal cancer. Med Oncol 29(2):919–927CrossRefPubMed
36.
Schmoll HJ et al (2012) ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol 23(10):2479–2516CrossRefPubMed
37.
38.
Li X et al (2012) Identification of aberrantly expressed miRNAs in rectal cancer. Oncol Rep 28(1):77–84PubMed
39.
Chen Z et al (2012) Differential miRNA expression profiling of rectal and colon cancers using deep sequencing. In: Proceedings of the 103rd annual meeting of the American Association for Cancer Research, Chicago, IL 2012, vol 72. AACR, Philadelphia
40.
Slattery ML et al (2015) An evaluation and replication of miRNAs with disease stage and colorectal cancer-specific mortality. Int J Cancer 137(2):428–438CrossRefPubMed
41.
Nielsen BS et al (2011) High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients. Clin Exp Metastasis 28(1):27–38CrossRefPubMed
42.
Nascimbeni R et al (2002) Risk of lymph node metastasis in T1 carcinoma of the colon and rectum. Dis Colon Rectum 45(2):200–206CrossRefPubMed
43.
Sakuragi M et al (2003) Predictive factors for lymph node metastasis in T1 stage colorectal carcinomas. Dis Colon Rectum 46(12):1626–1632CrossRefPubMed
44.
Peravali R, Naeem T, Wheeler J (2015) A single tertiary centre experience of t1 colorectal cancers—a retrospective analysis. Gut 64:A551CrossRef
45.
Zhang GJ et al (2014) miR20a is an independent prognostic factor in colorectal cancer and is involved in cell metastasis. Mol Med Rep 10(1):283–291CrossRefPubMed
46.
Brunet Vega A et al (2013) microRNA expression profile in stage III colorectal cancer: circulating miR-18a and miR-29a as promising biomarkers. Oncol Rep 30(1):320–326CrossRefPubMed
47.
Yu G et al (2012) Prognostic values of the miR-17-92 cluster and its paralogs in colon cancer. J Surg Oncol 106(3):232–237CrossRefPubMed
48.
49.
Mogilyansky E, Rigoutsos I (2013) The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ 20(12):1603–1614CrossRefPubMedPubMedCentral
50.
Fuziwara CS, Kimura ET (2015) Insights into regulation of the miR-17-92 cluster of miRNAs in Cancer. Front Med 2(2):64
51.
52.
Huang G et al (2017) miR-20a-directed regulation of BID is associated with the TRAIL sensitivity in colorectal cancer. Oncol Rep 37(1):571–578CrossRefPubMed
53.
Chai H et al (2011) miR-20a targets BNIP2 and contributes chemotherapeutic resistance in colorectal adenocarcinoma SW480 and SW620 cell lines. Acta Biochim Biophys Sin 43(3):217–225CrossRefPubMed
54.
Fujiya M et al (2014) microRNA-18a induces apoptosis in colon cancer cells via the autophagolysosomal degradation of oncogenic heterogeneous nuclear ribonucleoprotein A1. Oncogene 33(40):4847–4856CrossRefPubMed
55.
Humphreys KJ, McKinnon RA, Michael MZ (2014) miR-18a inhibits CDC42 and plays a tumour suppressor role in colorectal cancer cells. PLoS ONE 9(11):e112288CrossRefPubMedPubMedCentral
56.
Chen Y et al (2010) Altered expression of MiR-148a and MiR-152 in gastrointestinal cancers and its clinical significance. J Gastrointest Surg 14(7):1170–1179CrossRefPubMed
57.
Li B, Xie Z, Li B (2016) miR-152 functions as a tumor suppressor in colorectal cancer by targeting PIK3R3. Tumour Biol 37(8):10075–10084CrossRefPubMed
58.
Takahashi M et al (2012) The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer. PLoS ONE 7(10):e46684CrossRefPubMedPubMedCentral
59.
60.
61.
Oue N et al (2014) High miR-21 expression from FFPE tissues is associated with poor survival and response to adjuvant chemotherapy in colon cancer. Int J Cancer 134(8):1926–1934CrossRefPubMed
62.
Hansen TF et al (2014) Redefining high-risk patients with stage II colon cancer by risk index and microRNA-21: results from a population-based cohort. Br J Cancer 111(7):1285–1292CrossRefPubMedPubMedCentral
63.
Feng YH et al (2012) MicroRNA-21-mediated regulation of Sprouty2 protein expression enhances the cytotoxic effect of 5-fluorouracil and metformin in colon cancer cells. Int J Mol Med 29(5):920–926PubMed
64.
Asangani IA et al (2008) MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27(15):2128–2136CrossRefPubMed
65.
66.
67.
Kulda V et al (2010) Relevance of miR-21 and miR-143 expression in tissue samples of colorectal carcinoma and its liver metastases. Cancer Genet Cytogenet 200(2):154–160CrossRefPubMed
68.
69.
Zhu J et al (2014) MiR-20b, -21, and -130b inhibit PTEN expression resulting in B7-H1 over-expression in advanced colorectal cancer. Hum Immunol 75(4):348–353CrossRefPubMed
70.
Yamaguchi T et al (2014) Underexpression of miR-126 and miR-20b in hereditary and nonhereditary colorectal tumors. Int Soc Cell 87(1):58–66
71.
Chiang Y et al (2011) Aberrant expression of miR-203 and its clinical significance in gastric and colorectal cancers. J Gastrointest Surg 15(1):63–70CrossRefPubMed
72.
Zhao G et al (2015) miR-203 functions as a tumor suppressor by inhibiting epithelial to mesenchymal transition in ovarian cancer. J Cancer Sci Ther 7(2):34–43PubMedPubMedCentral
73.
Zhang X et al (2015) MicroRNA-203 is a prognostic indicator in bladder cancer and enhances chemosensitivity to cisplatin via apoptosis by targeting Bcl-w and survivin. PLoS ONE 10(11):e0143441CrossRefPubMedPubMedCentral
74.
Li J et al (2011) miR-203 reverses chemoresistance in p53-mutated colon cancer cells through downregulation of Akt2 expression. Cancer Lett 304(1):52–59CrossRefPubMed
75.
76.
77.
Della Vittoria Scarpati G et al (2014) Analysis of differential miRNA expression in primary tumor and stroma of colorectal cancer patients. Biomed Res Int 2014:840921CrossRefPubMedPubMedCentral
78.
Balcerczak E et al (2005) Cyclin D1 protein and CCND1 gene expression in colorectal cancer. Eur J Surg Oncol 31(7):721–726CrossRefPubMed
79.
Li L et al (2008) Association between phosphatidylinositol 3-kinase regulatory subunit p85alpha Met326Ile genetic polymorphism and colon cancer risk. Clin Cancer Res 14(3):633–637CrossRefPubMed
80.
Dweep H, Gretz N (2015) miRWalk2.0: a comprehensive atlas of microRNA-target interactions. Nat Methods 12(8):697CrossRefPubMed
81.
82.
83.
Wu X et al (2015) The potential value of miR-1 and miR-374b as biomarkers for colorectal cancer. Int J Clin Exp Pathol 8(3):2840–2851PubMedPubMedCentral
84.
Li H et al (2014) Clinical and biological significance of miR-378a-3p and miR-378a-5p in colorectal cancer. Eur J Cancer 50(6):1207–1221CrossRefPubMed
85.
86.
Wang YX et al (2010) Initial study of microRNA expression profiles of colonic cancer without lymph node metastasis. J Dig Dis 11(1):50–54CrossRefPubMed
87.
Chang KH et al (2011) MicroRNA signature analysis in colorectal cancer: identification of expression profiles in stage II tumors associated with aggressive disease. Int J Colorectal Dis 26(11):1415–1422CrossRefPubMed
88.
Motoyama K et al (2009) Over- and under-expressed microRNAs in human colorectal cancer. Int J Oncol 34(4):1069–1075PubMed
89.
Mosakhani N et al (2012) MicroRNA profiling differentiates colorectal cancer according to KRAS status. Genes Chromosom Cancer 51(1):1–9CrossRefPubMed
Metadata
Title
MicroRNAs and their role for T stage determination and lymph node metastasis in early colon carcinoma
Authors
Melanie Rammer
Gerald Webersinke
Sophie Haitchi-Petnehazy
Eva Maier
Hubert Hackl
Pornpimol Charoentong
Theodora Malli
Maria Steinmair
Andreas L. Petzer
Holger Rumpold
Publication date
01-10-2017
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 6-7/2017
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-017-9863-9

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