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

被引:41
作者
Finicelli, Mauro [1 ]
Benedetti, Giovanni [2 ]
Squillaro, Tiziana [1 ]
Pistilli, Barbara [2 ]
Marcellusi, Andrea [3 ]
Mariani, Paola [4 ]
Santinelli, Alfredo [5 ]
Latini, Luciano [2 ]
Galderisi, Umberto [6 ,7 ]
Giordano, Antonio [1 ,6 ]
机构
[1] Human Hlth Fdn, Spoleto, Italy
[2] Macerata Hosp, Dept Med Oncol, Macerata, Italy
[3] Univ Rome, Dept Stat, Rome, Italy
[4] MacerataHosp, Dept Pathol, Macerata, Italy
[5] Univ Politecn Marche, Dept Pathol, Ancona, Italy
[6] Temple Univ, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA
[7] Univ Naples 2, Dept Expt Med, Naples, Italy
关键词
Breast Cancer; Gene expression; Recurrence; SOX2; Stemness genes; TUMOR-INITIATING CELLS; TRANSCRIPTION FACTOR; RESISTANCE; PROMOTES; CARCINOMA; GROWTH; HETEROGENEITY; METASTASIS; SUBTYPES; COHORT;
D O I
10.18632/oncotarget.1936
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:9678 / 9688
页数:11
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