Abstract
BackgroundThe global gene regulator Special AT-rich sequence-binding protein1 (SATB1) has been reported to reprogramme tumour cells into a more malignant phenotype and associate with poor clinical outcome in several cancer forms. In this study, we investigated the molecular correlates and prognostic impact of SATB1 expression in human epithelial ovarian cancer (EOC).FindingsImmunohistochemical expression of SATB1 was examined in tissue microarrays with tumours from 151 incident EOC cases from two prospective, population-based cohorts. Benign-appearing fallopian tube epithelium from 32 cases was also analyzed. A multiplier of nuclear fraction and staining intensity of SATB1 was calculated. While barely expressed in tubal epithelium, nuclear SATB1 expression was denoted in 35/151 (23.2%) EOC cases. Spearman´s Rho test revealed an inverse correlation between SATB1 expression and histological grade (R = -0.22, p = 0.006) and a positive correlation with expression of dachshund 2 protein (R = 0.28, p = 0.001), phosphorylated Chek1 (R = 0.26, p = 0.002) and minichromosome maintenance protein 3 (R = 0.17, p = 0.042). Univariable Cox regression analysis revealed that SATB1 expression, while not prognostic in the full cohort, was associated with a reduced ovarian cancer-specific survival and 5-year overall survival in high grade tumours (n = 105) (HR = 2.14 and HR = 1.96, respectively). This association remained significant in multivariable analysis, adjusted for age and clinical stage (HR = 2.20 and HR = 2.06, respectively).ConclusionsThese results demonstrate that SATB1 expression is an independent factor of poor prognosis in high grade EOC and correlates in vivo with cellular processes involved in the maintenance of DNA integrity. The functional basis for these observations merits further investigation.
Highlights
The global gene regulator Special AT-rich sequence-binding protein1 (SATB1) has been reported to reprogramme tumour cells into a more malignant phenotype and associate with poor clinical outcome in several cancer forms
These results demonstrate that Special AT-rich sequence binding protein 1 (SATB1) expression is an independent factor of poor prognosis in high grade epithelial ovarian cancer (EOC) and correlates in vivo with cellular processes involved in the maintenance of DNA integrity
SATB1 expression was significantly associated with lower histological grade (Spearmans Rho = -0.22, p = 0.006) but not with age or clinical stage
Summary
This study provides further evidence of important regulatory functions of SATB1 in ovarian carcinogenesis and progression, and demonstrate SATB1 expression to be. Cox uni- and multivariable analysis of relative risks of death from ovarian cancer and overall death according to SATB1 expression in patients with high-grade carcinomas, irrespective of histological subtype (n = 105). Future studies should address the mechanistic basis for these functions in the context of molecular aberrations and chemotherapy response. Authors' contributions BN carried out the immunohistochemical stainings and evaluation, performed statistical analysis, and drafted the manuscript. CH carried out the immunohistochemical evaluation and helped to draft the manuscript. MU participated in the design of the study and provided technical assistance. KJ conceived of the study and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript
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