Abstract
BackgroundThe aim of this study was to investigate the expression of the nuclear receptor PPARγ, together with that of the cyclooxygenases Cox-1 and Cox-2, in breast cancer (BC) tissues and to correlate the data with several clinicobiological parameters including patient survival.MethodsIn a well characterized cohort of 308 primary BC, PPARγ, Cox-1 and Cox-2 cytoplasmic and nuclear expression were evaluated by immunohistochemistry. Correlations with clinicopathological and aggressiveness features were analyzed, as well as survival using Kaplan–Meier analysis.ResultsPPARγ was expressed in almost 58% of the samples with a predominant cytoplasmic location. Cox-1 and Cox-2 were exclusively cytoplasmic. Cytoplasmic PPARγ was inversely correlated with nuclear PPARγ and ER expression, but positively with Cox-1, Cox-2, and other high-risk markers of BC, e.g. HER2, CD133, and N-cadherin. Overall survival analysis demonstrated that cytoplasmic PPARγ had a strong correlation with poor survival in the whole cohort, and even stronger in the subgroup of patients with no Cox-1 expression where cytoplasmic PPARγ expression appeared as an independent marker of poor prognosis. In support of this cross-talk between PPARγ and Cox-1, we found that Cox-1 became a marker of good prognosis only when cytoplasmic PPARγ was expressed at high levels.ConclusionAltogether, these data suggest that the relative expression of cytoplasmic PPARγ and Cox-1 may play an important role in oncogenesis and could be defined as a potential prognosis marker to identify specific high risk BC subgroups.
Highlights
The aim of this study was to investigate the expression of the nuclear receptor Peroxisome proliferator-activated receptor γ (PPARγ), together with that of the cyclooxygenases Cox-1 and Cox-2, in breast cancer (BC) tissues and to correlate the data with several clinicobiological parameters including patient survival
In our primary BC cohort, PPARγ was predominantly expressed in cytoplasm of BC cells and may perform different roles in tumorigenesis according to its subcellular localization
Cytoplasmic PPARγ was strongly correlated with Cox-1 mainly, as well as with other bad prognosis markers (HER2, CD133, N-cadherin), contributing to explore their interactions during BC progression
Summary
The aim of this study was to investigate the expression of the nuclear receptor PPARγ, together with that of the cyclooxygenases Cox-1 and Cox-2, in breast cancer (BC) tissues and to correlate the data with several clinicobiological parameters including patient survival. Breast cancer (BC), the most commonly diagnosed malignant tumor in women, is the most frequent cause of cancer death worldwide [1] and a significant global public health problem. Few biomarkers have been well recognized in invasive breast carcinomas, including estrogen receptor (ER) and progesterone receptor (PR), which are associated with a better outcome and are predictive of endocrine sensitivity. Multifaceted mechanisms emerged in tumors, causing resistance to endocrine treatment in single or combination therapies [5]. Shao et al J Transl Med (2020) 18:94 comprehensive identification of more biomarkers and molecular targets is essential for optimal and personalized clinical BC management
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