Fig 2: Schematic illustration of the molecular mechanism of REG3B/REG3A-driven ADM.REG3B/REG3A binds to its receptor, EXTL3 receptor on the acinar cell membrane, and promotes ADM by activating the downstream RAS-RAF-MEK-ERK signaling pathway, in the absence of oncogenic Kras mutation. Targeting REG3B/REG3A, neutralizing its receptor EXTL3, or inhibiting downstream signaling molecules, such as B-RAF (LY3009120) or MEK1/2 (Trametinib), could interrupt the ADM process and potentially prevent early PDAC carcinogenesis.

Fig 3: Tissue microarray and immunohistochemistry staining of BRAF in esophageal cancer tissues. a Tissue microarray (105 cases of EC tissue and 75 cases of adjacent normal tissue;1 × magnification. b Strongly positive expression of BRAF in cancer tissues; 200 × magnification. c Weakly positive expression of BRAF in cancer tissues; 200 × magnification

Fig 4: Effect of BRAF on the clonal formation of esophageal cancer cells; ***P < 0.0001

Fig 5: Kaplan–Meier curve analysis for the overall survival (OS) of all AJCC clinical stage, AJCC clinical stage II and AJCC clinical stage III patients according to BRAF expression