Impact of disintegrin and metalloproteinase domain-containing protein 12 on pancreatic ductal adenocarcinoma treated with surgical resection and perioperative chemotherapy.

BACKGROUND/OBJECTIVES: A disintegrin and metalloproteinase domain-containing protein 12 (ADAM12) has been reported to influence tumor progression and chemosensitivity in human cancers. We assessed the prognostic impact of ADAM12 and its predictive value for neoadjuvant chemotherapy (NAC) in patients with pancreatic ductal adenocarcinoma (PDAC) treated with surgical resection. METHODS: ADAM12 expression was immunohistochemically examined in 428 patients with PDAC who underwent surgical resection. The association of ADAM12 expression with clinicopathological factors and survival was also analyzed. RESULTS: Patients with high ADAM12 expression exhibited significantly shorter median disease-free survival (DFS) (high ADAM12: 17.8 vs. low ADAM12: 37.9 months; P < 0.001) and overall survival (OS) (high ADAM12: 33.1 vs. low ADAM12: 65.0 months; P < 0.001). A multivariate analysis revealed that high ADAM12 expression was an independent risk factor for poor DFS (P < 0.001) and OS (P < 0.001) in all eligible patients. Of 100 patients who received neoadjuvant chemotherapy (NAC), high ADAM12 expression was significantly associated with poor DFS in a subset of patients treated with the nab-paclitaxel (PTX) neoadjuvant regimen (P = 0.03), whereas the prognostic value of ADAM12 was not evident in patients not treated with nab-PTX (P = 0.12). CONCLUSIONS: A negative prognostic value of high ADAM12 expression was observed in patients with PDAC treated with surgical resection, which was enhanced in patients treated with NAC, including nab-PTX. These results suggested that ADAM12 expression can predict nab-PTX chemosensitivity in PDAC and reflect PDAC progression.