Background: The mammalian NAD-dependent deacetylase sirtuin-1 family (named also silent information regulator or SIRT family, where NAD stands for “nicotinamide adenine dinucleotide” (NAD)) appears to have a dual role in several human cancers by modulating cell proliferation and death. This study examines how SIRT1 protein levels correlate with clinicopathological characteristics and survival outcomes in patients with breast cancer. Methods: A total of 407 BC formalin-fixed paraffin-embedded (FFPE) samples were collected from King Abdulaziz University Hospital, Saudi Arabia. SIRT1 was stained on tissue microarray slides using automated immunohistochemistry. Results: All BC subtypes expressed more nuclear SIRT1 proteins than their cytoplasm counterparts. In luminal A, luminal B, and TNBC, nuclear and cytoplasmic SIRT1 were highly associated (p < 0.001). Kaplan–Meier analysis showed reduced disease-specific survival (DSS) in H2BC with high SIRT1 nuclear expression (p = 0.001, log-rank). Moreover, the cytoplasmic expression of SIRT1 in HER2-positive BC was associated with a larger tumor size (p = 0.036) and lymph node metastasis (p = 0.045). Nuclear SIRT1 expression was also positively associated with lymph node metastasis (LNM) (p = 0.048). As low-grade tumors had a higher frequency of SIRT1 protein expression than other groups, SIRT1 expression was associated with a favorable prognosis in patients with luminal A BC (p < 0.001). Conclusions: SIRT1 expression seems to be involved in different molecular pathways either suppressing or promoting tumor growth depending on the subtype of BC. These molecular functions require further investigations and validation on larger BC cohorts.

Background: Tight junctions are major components of apical junction complexes and are crucial for the maintenance of cell polarity, healthy tissue architecture, adhesion, and permeability. These junctions include the claudin family of transmembrane proteins, which act as paracellular barriers to regulate selective permeability. Abnormal claudin expression disturbs cell adhesions and is associated with cancer through promoting cell invasion, migration, and metastasis. Claudin 6 (CLDN6) overexpression, in particular, is linked to several types of cancer with malignant phenotypes. The present study aimed to investigate the association between CLDN6 protein expression and its copy number variations (CNVs) with clinicopathological features and survival outcomes of ovarian cancer (OC) patients. Methods: A total of 114 formalin-fixed paraffin-embedded blocks from primary OC patients were used to construct tissue microarray slides. Automated immunostaining was used to assess CLDN6 protein expression levels, and next-generation knowledge discovery platforms were used to further evaluate CLDN6 CNV levels using The Cancer Genome Atlas open-source data. The relationships between CLDN6 CNVs and tumor stage, overall survival, disease-specific survival (DSS), and disease-free survival (DFS) were investigated. Results: This study demonstrated that CLDN6 had a mixed membranous-cytoplasmic expression pattern. The cytoplasmic expression of CLDN6 was significantly associated with tumor stage (p = 0.05), tumor size (p = 0.04), and recurrence (p = 0.05). In Univariate analysis, Kaplan–Meier analysis demonstrated that CLDN6 expression was significantly correlated with DFS (p = 0.01). OC patients with lower cytoplasmic CLDN6 expression levels lived longer and had lower recurrence rates. These findings were further confirmed through CLDN6 CNVs analysis, where OC with lower CLDN6 cytoplasmic expression positively correlated with longer DFS and DSS. No independent prognosticator was found when using Cox-regression multivariate analysis (p > 0.05). Conclusions: These results suggest CLDN6 as an interesting prognosticator to identify OC patients at a higher risk of recurrence in order to provide personalized management, alleviate the burden of this disease on women’s health, and improve their survival outcomes.