Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Human Pathology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Ann Surg. 2020 Apr;271(4):732-739. doi: 10.1097/SLA.0000000000002911.
To predict metachronous liver metastasis after pancreatectomy for pancreatic neuroendocrine neoplasms (Pan-NENs).
Liver metastasis determines the prognosis of patients with Pan-NENs, but no index exists in the WHO 2017 classification for this prediction.
Between April 2014 and March 2018, resected primary tumors from 20 patients with or without simultaneous liver metastasis were examined using genome-wide gene expression analysis. For validation analysis, resected primary tumors from 62 patients without simultaneous liver metastasis were examined for PAX6 expression.
Gene expression profiling revealed pancreatic beta cell genes (NES, -2.0; P < 0.001) as the most downregulated set in patients with simultaneous liver metastasis. In the test study, PAX6 was the most valuable index for liver metastasis (log FC, -3.683; P = 0.0096). Multivariate analysis identified PAX6 expression (hazard ratio, 0.2; P = 0.03) as an independent risk factor for metachronous liver metastasis-free survival (mLM-FS). The 5-year mLM-FS of patients with high versus low PAX6 expression was significantly better (95% vs 66%, respectively; P < 0.0001). The 5-year overall survival rate of was also better than in those with high versus low PAX6 expression (100% vs 87%, respectively). Patients with low PAX 6 expression were significantly younger and leaner, had a higher Ki-67 index (P = 0.01, 0.007, 0.008, respectively), and showed a higher mitotic rate than patients with high PAX6 expression.
Downregulated pancreatic beta cell genes involving PAX6 in primary tumors may predict mLM and poor overall survival after primary tumor resection in Pan-NEN patients.
预测胰腺神经内分泌肿瘤（Pan-NENs）患者行胰腺切除术后的肝转移。
肝转移决定了 Pan-NENs 患者的预后，但 2017 年世界卫生组织（WHO）分类中没有预测肝转移的指标。
2014 年 4 月至 2018 年 3 月，对 20 例同时伴有或不伴有肝转移的患者的切除原发肿瘤进行了全基因组基因表达分析。为了验证分析，对 62 例无同时肝转移的患者的切除原发肿瘤进行了 PAX6 表达检测。
基因表达谱分析显示，在同时伴有肝转移的患者中，胰腺β细胞基因（NES，-2.0；P<0.001）下调最为显著。在试验研究中，PAX6 是预测肝转移最有价值的指标（log FC，-3.683；P=0.0096）。多因素分析确定 PAX6 表达（危险比，0.2；P=0.03）是肝转移无复发生存（mLM-FS）的独立危险因素。高表达与低表达 PAX6 的患者 5 年 mLM-FS 差异显著（分别为 95%和 66%；P<0.0001）。高表达与低表达 PAX6 的患者 5 年总生存率也较好（分别为 100%和 87%）。低表达 PAX6 的患者年龄更小、更瘦，Ki-67 指数更高（P=0.01、0.007、0.008），有丝分裂率也高于高表达 PAX6 的患者。
原发肿瘤中下调的胰腺β细胞基因包括 PAX6，可能预测 Pan-NEN 患者行胰腺切除术后的 mLM 和整体预后不良。
