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

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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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Abbreviations

Adj. p:

Adjusted p value

BID:

BH3 interacting domain death agonist

BNIP2:

BCL2 interacting protein 2

CCND1:

Cyclin D1

CDC42:

Cell cycle division 42

CO:

Control

Corr. p:

Nested F corrected p value

COX-2:

Cyclooxygenase 2

CRC:

Colorectal cancer

EIF5A2:

Eukaryotic translation initiation factor 5A2

FC:

Fold change

FFPE:

Formalin-fixed paraffin-embedded

hnRNP A1:

Heterogeneous nuclear ribonucleoprotein A1

IQR:

Interquartile range

KRAS:

KRAS proto-oncogene, GTPase

miRNA:

MicroRNA

PDCD4:

Programmed cell death 4

PGE2:

Prostaglandin E2

PIK3R3:

Phosphoinositide-3-kinase regulatory subunit 3

PTEN:

Phosphatase and tensin homolog

qPCR:

Quantitative real-time polymerase chain reaction

SPRY2:

Sprouty RTK signaling antagonist 2

TERT:

Telomerase reverse transcriptase

TGFBRII:

TGF-β receptor II

TGF-β:

Transforming growth factor beta

TNM staging:

Tumor-node-metastasis staging

TSP-1:

Thrombospondin

TU:

Tumor

UICC:

Union for international cancer control

VIM:

Vimentin

ZNF217:

Zinc finger protein 217

ΔCq:

Delta threshold cycle

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This project received a research grant from “Krebshilfe Oberösterreich”.

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Correspondence to Holger Rumpold.

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Rammer, M., Webersinke, G., Haitchi-Petnehazy, S. et al. MicroRNAs and their role for T stage determination and lymph node metastasis in early colon carcinoma. Clin Exp Metastasis 34, 431–440 (2017). https://doi.org/10.1007/s10585-017-9863-9

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