Oncotarget

Research Papers:

Expression of stemness genes in primary breast cancer tissues: the role of SOX2 as a prognostic marker for detection of early recurrence

Mauro Finicelli, Giovanni Benedetti, Tiziana Squillaro, Barbara Pistilli, Andrea Marcellusi, Paola Mariani, Alfredo Santinelli, Luciano Latini, Umberto Galderisi, _ Antonio Giordano

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Oncotarget. 2014; 5:9678-9688. https://doi.org/10.18632/oncotarget.1936

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Abstract

Mauro Finicelli1,*, Giovanni Benedetti2,*, Tiziana Squillaro1, Barbara Pistilli2, Andrea Marcellusi3, Paola Mariani4, Alfredo Santinelli5, Luciano Latini2, Umberto Galderisi6,7, Antonio Giordano1,6

1 Human Health Foundation, Spoleto, Italy

2 Department of Medical Oncology,Macerata Hospital, Macerata, Italy

3 Department of Statistics, University of Rome, Rome, Italy

4 Department of Pathology,MacerataHospital, Macerata, Italy

5 Department of Pathology Università Politecnica delle Marche, Ancona, Italy

6 Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA

7 Department of Experimental Medicine, Second University of Naples, Naples, Italy

* These authors contributed equally to this work

Correspondence:

Umberto Galderisi, email:

Keywords: Breast Cancer; Gene expression; Recurrence; SOX2; Stemness genes

Received: April 19, 2014 Accepted: April 30, 2014 Published: May 1, 2014

Abstract

The events leading to breast cancer (BC) progression or recurrence are not completely understood and new prognostic markers aiming at identifying high risk-patients and to develop suitable therapy are highly demanded. Experimental evidences found in cancer cells a deregulated expression of some genes involved in governance of stem cell properties and demonstrated a relationship between stemness genes overexpression and poorly differentiated BC subtypes.

In the present study 140 primary invasive BC specimens were collected. The expression profiles of 13 genes belonging to the OCT3/SOX2/NANOG/KLF4 core circuitry by RT-PCR were analyzed and any correlation between their expression and the BC clinic-pathological features (CPfs) and prognosis was investigated.

In our cohort (117 samples), NANOG, GDF3 and SOX2 significantly correlated with grade 2, Nodes negative status and higher KI67 proliferation index, respectively (p=0.019, p=0.029, p= 0.035). According to multivariate analysis, SOX2 expression resulted independently associated with increased risk of recurrence (HR= 2,99; p= p=0,004) as well as Nodes status (HR=2,44; p=0,009) and T-size >1 (HR=1,77; p=0,035) .

Our study provides further proof of the suitable use of stemness genes in BC management. Interestingly, a prognostic role of SOX2, which seems to be a suitable marker of early recurrence irrespective of other clinicopathological features.


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