TY - JOUR
T1 - Intra-tumor heterogeneity of microRNA-92a, microRNA-375 and microRNA-424 in colorectal cancer
AU - Jepsen, Rikke Karlin
AU - Novotny, Guy Wayne
AU - Klarskov, Louise Laurberg
AU - Christensen, Ib Jarle
AU - Riis, Lene Buhl
AU - Høgdall, Estrid
PY - 2016
Y1 - 2016
N2 - Various microRNAs (miRNAs) have been investigated in order to improve diagnostics and risk assessment in colorectal cancer (CRC). To clarify the potential of miRNA profiling in CRC, knowledge of intra-tumor heterogeneity in expression levels is crucial. The study aim was to estimate the intra-tumor variance of three selected miRNAs: miR-92a, miR-375 and miR-424 in CRC tissue. Material and methods: A retrospective study on archived formalin-fixed paraffin embedded tissue from 9 patients with CRC. miRNA tissue expression levels were analyzed by qRT-PCR on tissue representing luminal, central and invasive border zones. Variance components were estimated based on Cp values using mixed modeling and presented as coefficients of variation (CV). Results: Intra-tumor variance was approximately half of the variance observed between patients with a mean intra-tumor CV of 56.4% (range 33.1-77.1%) and a mean inter-patient CV of 101.7% (range 48.8-152.7%). Furthermore we found a significant systematic difference in expression levels between tumor zones for miR-92a and miR-375 with a luminal-invasive difference equal to 0.60 Cp (95% CI: 0.30-0.89, p = 0.0003) for miR-92a and a luminal-invasive difference equal to 0.78 Cp (95% CI: 0.10-1.46, p = 0.027) for miR-375. Conclusion. While the intra-tumor variance of miR-92a, miR-375 and miR-424 is substantial, it only constitutes approximately 30% of the total variation. Functional deregulation between tumor zones might contribute to variations in measured expression levels, and thus knowledge of specific intra-tumor expression patterns is crucial in tissue sampling for research as well as in future diagnostics.
AB - Various microRNAs (miRNAs) have been investigated in order to improve diagnostics and risk assessment in colorectal cancer (CRC). To clarify the potential of miRNA profiling in CRC, knowledge of intra-tumor heterogeneity in expression levels is crucial. The study aim was to estimate the intra-tumor variance of three selected miRNAs: miR-92a, miR-375 and miR-424 in CRC tissue. Material and methods: A retrospective study on archived formalin-fixed paraffin embedded tissue from 9 patients with CRC. miRNA tissue expression levels were analyzed by qRT-PCR on tissue representing luminal, central and invasive border zones. Variance components were estimated based on Cp values using mixed modeling and presented as coefficients of variation (CV). Results: Intra-tumor variance was approximately half of the variance observed between patients with a mean intra-tumor CV of 56.4% (range 33.1-77.1%) and a mean inter-patient CV of 101.7% (range 48.8-152.7%). Furthermore we found a significant systematic difference in expression levels between tumor zones for miR-92a and miR-375 with a luminal-invasive difference equal to 0.60 Cp (95% CI: 0.30-0.89, p = 0.0003) for miR-92a and a luminal-invasive difference equal to 0.78 Cp (95% CI: 0.10-1.46, p = 0.027) for miR-375. Conclusion. While the intra-tumor variance of miR-92a, miR-375 and miR-424 is substantial, it only constitutes approximately 30% of the total variation. Functional deregulation between tumor zones might contribute to variations in measured expression levels, and thus knowledge of specific intra-tumor expression patterns is crucial in tissue sampling for research as well as in future diagnostics.
KW - Colorectal cancer
KW - Intra-tumor heterogeneity
KW - Intra-tumor variance
KW - MicroRNA
U2 - 10.1016/j.yexmp.2015.12.004
DO - 10.1016/j.yexmp.2015.12.004
M3 - Journal article
C2 - 26681654
AN - SCOPUS:84949843839
SN - 0014-4800
VL - 100
SP - 125
EP - 131
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
IS - 1
ER -
