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2016 ; 11
(6
): e0156919
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Intratumoral Heterogeneity of MicroRNA Expression in Rectal Cancer
#MMPMID27258547
Eriksen AH
; Andersen RF
; Nielsen BS
; Sørensen FB
; Appelt AL
; Jakobsen A
; Hansen TF
PLoS One
2016[]; 11
(6
): e0156919
PMID27258547
show ga
INTRODUCTION: An increasing number of studies have investigated microRNAs
(miRNAs) as potential markers of diagnosis, treatment and prognosis. So far,
agreement between studies has been minimal, which may in part be explained by
intratumoral heterogeneity of miRNA expression. The aim of the present study was
to assess the heterogeneity of a panel of selected miRNAs in rectal cancer, using
two different technical approaches. MATERIALS AND METHODS: The expression of the
investigated miRNAs was analysed by real-time quantitative polymerase chain
reaction (RT-qPCR) and in situ hybridization (ISH) in tumour specimens from 27
patients with T3-4 rectal cancer. From each tumour, tissue from three different
luminal localisations was examined. Inter- and intra-patient variability was
assessed by calculating intraclass correlation coefficients (ICCs). Correlations
between RT-qPCR and ISH were evaluated using Spearman's correlation. RESULTS:
ICCsingle (one sample from each patient) was higher than 50% for miRNA-21 and
miRNA-31. For miRNA-125b, miRNA-145, and miRNA-630, ICCsingle was lower than 50%.
The ICCmean (mean of three samples from each patient) was higher than 50% for
miRNA-21(RT-qPCR and ISH), miRNA-125b (RT-qPCR and ISH), miRNA-145 (ISH),
miRNA-630 (RT-qPCR), and miRNA-31 (RT-qPCR). For miRNA-145 (RT-qPCR) and
miRNA-630 (ISH), ICCmean was lower than 50%. Spearman correlation coefficients,
comparing results obtained by RT-qPCR and ISH, respectively, ranged from 0.084 to
0.325 for the mean value from each patient, and from -0.085 to 0.515 in the
section including the deepest part of the tumour. CONCLUSION: Intratumoral
heterogeneity may influence the measurement of miRNA expression and consequently
the number of samples needed for representative estimates. Our findings with two
different methods suggest that one sample is sufficient for adequate assessment
of miRNA-21 and miRNA-31, whereas more samples would improve the assessment of
miRNA-125b, miRNA-145, and miRNA-630. Interestingly, we found a poor correlation
between the expression estimates obtained by RT-qPCR and ISH, respectively.
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