title: Expression of stemness genes in primary breast cancer tissues: the role of SOX2 as a prognostic marker for detection of early recurrence.
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.
authors.affiliation: Human Health Foundation, Spoleto, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Finicelli
authors.affiliation: Department of Medical Oncology, Macerata Hospital, Macerata, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Benedetti
authors.affiliation: Human Health Foundation, Spoleto, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Squillaro
authors.affiliation: Department of Medical Oncology, Macerata Hospital, Macerata, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pistilli
authors.affiliation: Department of Statistics, University of Rome, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Marcellusi
authors.affiliation: Department of Pathology, Macerata Hospital, Macerata, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Mariani
authors.affiliation: Department of Pathology Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Santinelli
authors.affiliation: Department of Medical Oncology, Macerata Hospital, Macerata, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Latini
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA. Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Galderisi
authors.affiliation: Human Health Foundation, Spoleto, Italy. Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000090062:Kruppel-Like Factor 4; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D011379:Prognosis; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors