Pluripotent stem cell miRNAs and metastasis in invasive breast cancer

Stefano Volinia; Gerard Nuovo; Alessandra Drusco; Stefan Costinean; Ramzey Abujarour; Caroline Desponts; Michela Garofalo; Raffaele Baffa; Rami Aeqilan; Kati Maharry; Maria Elena Sana Ramiro Garzon; Gianpiero Di Leva; Pierluigi Gasparini; Paola Dama; Jlenia Marchesini; Marco Galasso; Marco Manfrini; Carlotta Zerbinati; Fabio Corrà; Timothy Wise; Sylwia E. Wojcik; Maurizio Previati; Flavia Pichiorri; Nicola Zanesi; Hansjuerg Alder; Jeff Palatini; Kay F. Huebner; Charles L. Shapiro; Massimo Negrini; Andrea Vecchione; Anne L. Rosenberg; Carlo M. Croce

doi:https://doi.org/10.1093/jnci/dju324

Pluripotent stem cell miRNAs and metastasis in invasive breast cancer

Stefano Volinia, Gerard Nuovo, Alessandra Drusco, Stefan Costinean, Ramzey Abujarour, Caroline Desponts, Michela Garofalo, Raffaele Baffa, Rami Aeqilan, Kati Maharry, Maria Elena Sana Ramiro Garzon, Gianpiero Di Leva, Pierluigi Gasparini, Paola Dama, Jlenia Marchesini, Marco Galasso, Marco Manfrini, Carlotta Zerbinati, Fabio Corrà, Timothy WiseSylwia E. Wojcik, Maurizio Previati, Flavia Pichiorri, Nicola Zanesi, Hansjuerg Alder, Jeff Palatini, Kay F. Huebner, Charles L. Shapiro, Massimo Negrini, Andrea Vecchione, Anne L. Rosenberg, Carlo M. Croce

Research output: Contribution to journal › Article › peer-review

Abstract

Background The purpose of this study is to determine whether microRNA for pluripotent stem cells are also expressed in breast cancer and are associated with metastasis and outcome. Methods We studied global microRNA profiles during differentiation of human embryonic stem cells (n =26) and in breast cancer patients (n = 33) and human cell lines (n = 35). Using in situ hybridization, we then investigated MIR302 expression in 318 untreated breast cancer patients (test cohort, n = 22 and validation cohort, n = 296). In parallel, using next-generation sequencing data from breast cancer patients (n = 684), we assessed microRNA association with stem cell markers. All statistical tests were two-sided. Results In healthy tissues, the MIR302 (high)/MIR203 (low) asymmetry was exclusive for pluripotent stem cells. MIR302 was expressed in a small population of cancer cells within invasive ductal carcinoma, but not in normal breast (P <. 001). Furthermore, MIR302 was expressed in the tumor cells together with stem cell markers, such as CD44 and BMI1. Conversely, MIR203 expression in 684 breast tumors negatively correlated with CD44 (Spearman correlation, Rho = -0.08, P =. 04) and BMI1 (Rho = -0.11, P =. 004), but positively correlated with differentiation marker CD24 (Rho = 0.15, P <. 001). Primary tumors with lymph node metastasis had cancer cells showing scattered expression of MIR302 and widespread repression of MIR203. Finally, overall survival was statistically significantly shorter in patients with MIR302-positive cancer cells (P =. 03). Conclusions In healthy tissues the MIR302(high)/MIR203(low) asymmetry was characteristic of embryonic and induced pluripotency. In invasive ductal carcinoma, the MIR302/MIR203 asymmetry was associated with stem cell markers, metastasis, and shorter survival.

Original language	English
Journal	Journal of the National Cancer Institute
Volume	106
Issue number	12
DOIs	https://doi.org/10.1093/jnci/dju324
State	Published - 1 Dec 2014
Externally published	Yes

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://doi.org/10.1093/jnci/dju324

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Volinia, S., Nuovo, G., Drusco, A., Costinean, S., Abujarour, R., Desponts, C., Garofalo, M., Baffa, R., Aeqilan, R., Maharry, K., Garzon, M. E. S. R., Di Leva, G., Gasparini, P., Dama, P., Marchesini, J., Galasso, M., Manfrini, M., Zerbinati, C., Corrà, F., ... Croce, C. M. (2014). Pluripotent stem cell miRNAs and metastasis in invasive breast cancer. Journal of the National Cancer Institute, 106(12). https://doi.org/10.1093/jnci/dju324

@article{91bec8070a5b4ab3844015dab5ae146a,

title = "Pluripotent stem cell miRNAs and metastasis in invasive breast cancer",

abstract = "Background The purpose of this study is to determine whether microRNA for pluripotent stem cells are also expressed in breast cancer and are associated with metastasis and outcome. Methods We studied global microRNA profiles during differentiation of human embryonic stem cells (n =26) and in breast cancer patients (n = 33) and human cell lines (n = 35). Using in situ hybridization, we then investigated MIR302 expression in 318 untreated breast cancer patients (test cohort, n = 22 and validation cohort, n = 296). In parallel, using next-generation sequencing data from breast cancer patients (n = 684), we assessed microRNA association with stem cell markers. All statistical tests were two-sided. Results In healthy tissues, the MIR302 (high)/MIR203 (low) asymmetry was exclusive for pluripotent stem cells. MIR302 was expressed in a small population of cancer cells within invasive ductal carcinoma, but not in normal breast (P <. 001). Furthermore, MIR302 was expressed in the tumor cells together with stem cell markers, such as CD44 and BMI1. Conversely, MIR203 expression in 684 breast tumors negatively correlated with CD44 (Spearman correlation, Rho = -0.08, P =. 04) and BMI1 (Rho = -0.11, P =. 004), but positively correlated with differentiation marker CD24 (Rho = 0.15, P <. 001). Primary tumors with lymph node metastasis had cancer cells showing scattered expression of MIR302 and widespread repression of MIR203. Finally, overall survival was statistically significantly shorter in patients with MIR302-positive cancer cells (P =. 03). Conclusions In healthy tissues the MIR302(high)/MIR203(low) asymmetry was characteristic of embryonic and induced pluripotency. In invasive ductal carcinoma, the MIR302/MIR203 asymmetry was associated with stem cell markers, metastasis, and shorter survival.",

author = "Stefano Volinia and Gerard Nuovo and Alessandra Drusco and Stefan Costinean and Ramzey Abujarour and Caroline Desponts and Michela Garofalo and Raffaele Baffa and Rami Aeqilan and Kati Maharry and Garzon, {Maria Elena Sana Ramiro} and {Di Leva}, Gianpiero and Pierluigi Gasparini and Paola Dama and Jlenia Marchesini and Marco Galasso and Marco Manfrini and Carlotta Zerbinati and Fabio Corr{\`a} and Timothy Wise and Wojcik, {Sylwia E.} and Maurizio Previati and Flavia Pichiorri and Nicola Zanesi and Hansjuerg Alder and Jeff Palatini and Huebner, {Kay F.} and Shapiro, {Charles L.} and Massimo Negrini and Andrea Vecchione and Rosenberg, {Anne L.} and Croce, {Carlo M.}",

note = "Publisher Copyright: {\textcopyright} The Author 2014.",

year = "2014",

month = dec,

day = "1",

doi = "https://doi.org/10.1093/jnci/dju324",

language = "الإنجليزيّة",

volume = "106",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "12",

}

Volinia, S, Nuovo, G, Drusco, A, Costinean, S, Abujarour, R, Desponts, C, Garofalo, M, Baffa, R, Aeqilan, R, Maharry, K, Garzon, MESR, Di Leva, G, Gasparini, P, Dama, P, Marchesini, J, Galasso, M, Manfrini, M, Zerbinati, C, Corrà, F, Wise, T, Wojcik, SE, Previati, M, Pichiorri, F, Zanesi, N, Alder, H, Palatini, J, Huebner, KF, Shapiro, CL, Negrini, M, Vecchione, A, Rosenberg, AL & Croce, CM 2014, 'Pluripotent stem cell miRNAs and metastasis in invasive breast cancer', Journal of the National Cancer Institute, vol. 106, no. 12. https://doi.org/10.1093/jnci/dju324

TY - JOUR

T1 - Pluripotent stem cell miRNAs and metastasis in invasive breast cancer

AU - Volinia, Stefano

AU - Nuovo, Gerard

AU - Drusco, Alessandra

AU - Costinean, Stefan

AU - Abujarour, Ramzey

AU - Desponts, Caroline

AU - Garofalo, Michela

AU - Baffa, Raffaele

AU - Aeqilan, Rami

AU - Maharry, Kati

AU - Garzon, Maria Elena Sana Ramiro

AU - Di Leva, Gianpiero

AU - Gasparini, Pierluigi

AU - Dama, Paola

AU - Marchesini, Jlenia

AU - Galasso, Marco

AU - Manfrini, Marco

AU - Zerbinati, Carlotta

AU - Corrà, Fabio

AU - Wise, Timothy

AU - Wojcik, Sylwia E.

AU - Previati, Maurizio

AU - Pichiorri, Flavia

AU - Zanesi, Nicola

AU - Alder, Hansjuerg

AU - Palatini, Jeff

AU - Huebner, Kay F.

AU - Shapiro, Charles L.

AU - Negrini, Massimo

AU - Vecchione, Andrea

AU - Rosenberg, Anne L.

AU - Croce, Carlo M.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Background The purpose of this study is to determine whether microRNA for pluripotent stem cells are also expressed in breast cancer and are associated with metastasis and outcome. Methods We studied global microRNA profiles during differentiation of human embryonic stem cells (n =26) and in breast cancer patients (n = 33) and human cell lines (n = 35). Using in situ hybridization, we then investigated MIR302 expression in 318 untreated breast cancer patients (test cohort, n = 22 and validation cohort, n = 296). In parallel, using next-generation sequencing data from breast cancer patients (n = 684), we assessed microRNA association with stem cell markers. All statistical tests were two-sided. Results In healthy tissues, the MIR302 (high)/MIR203 (low) asymmetry was exclusive for pluripotent stem cells. MIR302 was expressed in a small population of cancer cells within invasive ductal carcinoma, but not in normal breast (P <. 001). Furthermore, MIR302 was expressed in the tumor cells together with stem cell markers, such as CD44 and BMI1. Conversely, MIR203 expression in 684 breast tumors negatively correlated with CD44 (Spearman correlation, Rho = -0.08, P =. 04) and BMI1 (Rho = -0.11, P =. 004), but positively correlated with differentiation marker CD24 (Rho = 0.15, P <. 001). Primary tumors with lymph node metastasis had cancer cells showing scattered expression of MIR302 and widespread repression of MIR203. Finally, overall survival was statistically significantly shorter in patients with MIR302-positive cancer cells (P =. 03). Conclusions In healthy tissues the MIR302(high)/MIR203(low) asymmetry was characteristic of embryonic and induced pluripotency. In invasive ductal carcinoma, the MIR302/MIR203 asymmetry was associated with stem cell markers, metastasis, and shorter survival.

AB - Background The purpose of this study is to determine whether microRNA for pluripotent stem cells are also expressed in breast cancer and are associated with metastasis and outcome. Methods We studied global microRNA profiles during differentiation of human embryonic stem cells (n =26) and in breast cancer patients (n = 33) and human cell lines (n = 35). Using in situ hybridization, we then investigated MIR302 expression in 318 untreated breast cancer patients (test cohort, n = 22 and validation cohort, n = 296). In parallel, using next-generation sequencing data from breast cancer patients (n = 684), we assessed microRNA association with stem cell markers. All statistical tests were two-sided. Results In healthy tissues, the MIR302 (high)/MIR203 (low) asymmetry was exclusive for pluripotent stem cells. MIR302 was expressed in a small population of cancer cells within invasive ductal carcinoma, but not in normal breast (P <. 001). Furthermore, MIR302 was expressed in the tumor cells together with stem cell markers, such as CD44 and BMI1. Conversely, MIR203 expression in 684 breast tumors negatively correlated with CD44 (Spearman correlation, Rho = -0.08, P =. 04) and BMI1 (Rho = -0.11, P =. 004), but positively correlated with differentiation marker CD24 (Rho = 0.15, P <. 001). Primary tumors with lymph node metastasis had cancer cells showing scattered expression of MIR302 and widespread repression of MIR203. Finally, overall survival was statistically significantly shorter in patients with MIR302-positive cancer cells (P =. 03). Conclusions In healthy tissues the MIR302(high)/MIR203(low) asymmetry was characteristic of embryonic and induced pluripotency. In invasive ductal carcinoma, the MIR302/MIR203 asymmetry was associated with stem cell markers, metastasis, and shorter survival.

UR - http://www.scopus.com/inward/record.url?scp=84922391474&partnerID=8YFLogxK

U2 - https://doi.org/10.1093/jnci/dju324

DO - https://doi.org/10.1093/jnci/dju324

M3 - مقالة

C2 - 25306216

SN - 0027-8874

VL - 106

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 12

ER -

Pluripotent stem cell miRNAs and metastasis in invasive breast cancer

Abstract

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