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

解整合素和金属蛋白酶结构域蛋白12对胰腺导管腺癌手术切除和围手术期化疗的影响

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作者:Takuya Sakoda, Kenichiro Uemura, Naru Kondo, Tatsuaki Sumiyoshi, Kenjiro Okada, Shingo Seo, Hiroyuki Otsuka, Yoshiaki Murakami, Shinya Takahashi

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.

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.

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