Nishizawa Nobuyuki, Kumamoto Yusuke, Katoh Hiroshi, Ushiku Hideki, Yokoi Keigo, Tanaka Toshimichi, Ishii Satoru, Igarashi Kazuharu, Tajima Hiroshi, Kaizu Takashi, Yoshida Tsutomu, Saegusa Makoto, Watanabe Masahiko, Yamashita Keishi
Department of Surgery, Kitasato University Hospital, Sagamihara, Kanagawa 252-0374, Japan.
Department of Pathology, Kitasato University Hospital, Sagamihara, Kanagawa 252-0374, Japan.
Oncol Lett. 2019 Feb;17(2):2141-2150. doi: 10.3892/ol.2018.9839. Epub 2018 Dec 17.
We previously reported that the dissected pancreatic tissue margin (DPM) and the preoperative serum level of carbohydrate antigen 19-9 (preCA19-9) were independent prognostic factors in pancreatic ductal adenocarcinoma (PDAC). In the current study, the prognostic relevance of these factors, including their molecular associations, were validated. A total of 161 patients with PDAC underwent a pancreatectomy between 1986 and 2013, and a multivariate Cox proportional hazards model and a propensity score-based model validated the prognostic importance of DPM. The prognostic factors were compared with the mutation profiles of the and genes. Univariate prognostic analysis of disease-specific survival (DSS) demonstrated that DPM (P<0.0001), preCA19-9 (P<0.0001) and Union for International Cancer Control (UICC) stage (P<0.0001), were all significantly associated with poor outcome in PDAC. A multivariate Cox proportional hazards model confirmed that preCA19-9 (P=0.0002) and DPM (P=0.0002) remained as prognostic factors independent of UICC stage (P=0.0015). The combination of preCA19-9 and DPM to predict prognosis could accurately identify the long-term survivors of PDAC (70% 5-year DSS), and a multivariate logistic regression model identified that DPM was the most effective predictor of mortality. The prognostic relevance of DPM was also confirmed (P=0.0008) through propensity score-based background adjustment of patient bias. gene mutation was significantly associated with DPM (P=0.0002), and DPM-positive patients demonstrated recurrence of distant metastasis in 67% of cases. Therefore, DPM is a critical prognostic indicator in PDAC. In combination with preCA19-9, DPM may be useful to identify long-term survivors of PDAC. Furthermore, to the best of our knowledge, the current study was the first to discover that DPM can represent a poor prognosis based putatively on its association with the gene mutation.
我们之前报道过，胰腺组织切除边缘（DPM）和术前血清糖类抗原19-9水平（preCA19-9）是胰腺导管腺癌（PDAC）的独立预后因素。在本研究中，对这些因素的预后相关性，包括它们的分子关联，进行了验证。1986年至2013年间，共有161例PDAC患者接受了胰腺切除术，多变量Cox比例风险模型和基于倾向评分的模型验证了DPM的预后重要性。将这些预后因素与KRAS和NRAS基因的突变谱进行了比较。疾病特异性生存（DSS）的单变量预后分析表明，DPM（P<0.0001）、preCA19-9（P<0.0001）和国际癌症控制联盟（UICC）分期（P<0.0001）均与PDAC的不良预后显著相关。多变量Cox比例风险模型证实，preCA19-9（P=0.0002）和DPM（P=0.0002）仍然是独立于UICC分期（P=0.0015）的预后因素。preCA19-9和DPM联合预测预后能够准确识别PDAC的长期生存者（5年DSS为70%），多变量逻辑回归模型确定DPM是死亡率最有效的预测指标。通过基于倾向评分的患者偏倚背景调整，也证实了DPM的预后相关性（P=0.0008）。KRAS基因突变与DPM显著相关（P=0.0002），DPM阳性患者67%出现远处转移复发。因此，DPM是PDAC的关键预后指标。与preCA19-9联合，DPM可能有助于识别PDAC的长期生存者。此外，据我们所知，本研究首次发现DPM可能因其与KRAS基因突变的关联而代表不良预后。
