Background: Neurogenic locus notch homology 4 (Notch-4) is crucial in maintaining stem cells. Special AT-rich sequence-binding protein 2 (SATB-2) is a transcription factor that binds to the nuclear matrix and serves various functions, including brain development. Glutaminase-1 (GLS-1) plays a pivotal role in cancer cell metabolism, growth, and proliferation. This study aims to assess the expression of these markers in colorectal cancer, establishing correlations with clinicopathological characteristics and patient survival.Method: In this retrospective study, we retrieved and analyzed 68 formalin-fixed, paraffin-embedded blocks of primary colorectal adenocarcinoma, not otherwise specified cases, and adjacent normal mucosa. Notch-4, SATB-2 and GLS-1 expressions were analyzed using immunohistochemistry at the Zagazig School of Medicine, Egypt.Results: High expressions of Notch-4 and GLS-1 and low expression of SATB-2 were observed in colonic adenocarcinoma but not in adjacent non-neoplastic mucosa (P < 0.001). High expressions of Notch-4 and GLS-1, along with low expression of SATB-2, were associated with a higher tumor grade, advanced stage (P < 0.001), lymphovascular invasion, lymph node metastasis, and poor disease-free survival and overall survival rates (P < 0.001).Conclusion: High expression of Notch-4 and GLS-1 is correlated with a poor prognosis in colorectal cancer, while high expression of SATB-2 is associated with a favorable prognosis for colorectal carcinoma. These markers can aid in predicting tumor prognosis and guiding targeted therapy for colorectal carcinoma
