The protein participates in the regulation of gene activity, cell proliferation, differentiation and death [7]. However, the SMAD3-mediated TGF-\(\beta\) signaling pathway is also involved in the induction of tumor angiogenesis and the promotion of tissue invasion and metastasis [8; 9]. The many cellular processes, including organ development, differentiation and tissue homeostasis, are controlled by the Wnt/\(\beta\)-catenin signaling pathway. Aberrant Wnt/\(\beta\)-catenin signaling can lead to developmental defects and cancer progression. \(\beta\)-catenin (encoded by CTNNB1 gen) is a key molecule in this pathway. Stabilized \(\beta\)-catenin accumulates in the cytoplasm and translocates to the nucleus, where it binds the TCF/LEF family members and induces the transcription of target genes. Many studies have reported that overexpression of \(\beta\)-catenin is associated with several human cancers [10; 11; 12]. However, the role of \(\beta\)-catenin expression in PDAC is somewhat controversial [13]. Special AT-rich sequence-binding protein 1 (SATB1) is a higher-order chromatin organizer and a global transcriptional regulator. SATB1 may regulate whole sets of genes, even those located on distant chromosomes, by altering the functional organization of the DNA sequence. In addition, SATB1 is engaged in post-transcriptional modifications, such as phosphorylation or acetylation, conferring its ability to act as a repressor or activator of gene expression [14]. SATB1 is known to play a vital role in the differentiation, embryonic development and maturation of thymocytes [15]. Furthermore, our team has revealed that the SATB1/F-actin complex is involved in the active cell death of both tumor [16] and non-tumor cells [17]. However, it may also contribute to tumor progression and metastasis. Many recent studies have shown that the abnormal expression of SATB1 is frequently associated with clinicopathological features and patient survival, but its clinical value in PDAC is still underexplored [18; 19; 20; 21; 22; 23; 24]. Similar to other malignancies, uncontrolled cell proliferation is induced in PDAC by the alternating function of different intracellular signaling pathways' components. As demonstrated in previous studies, SATB1, SMAD3, Ezrin and \(\beta\)-catenin play an important role in regulating cell proliferation, migration and apoptosis, which are strongly implicated in carcinogenesis. In this study, we selected these proteins due to the fact that they may be related by their respective roles and overlapping signaling cascades in tumor cells; however, their joint expression has not been previously evaluated in clinical samples of PDAC. Therefore, the aim of this research was to explore the prognostic value of the single and combined expression of SATB1, SMAD3, Ezrin and \(\beta\)-catenin in PDAC. Protein expression was evaluated by immunochemistry in the institutional tissue macroarrays (TMAs), while mRNA expression used publicly available TCGA data. Both were correlated with clinicopathological parameters and patient outcome (overall survival, OS). Finally,protein-protein interaction (PPI) network for \(\beta\)-catenin, Ezrin, SATB1, SMAD3 and their 50 neighbors was constructed and functionally annotated to predict biological functions and pathways possibly related to examined factors in PAC.