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Background: Pancreatic cancer has an extremely poor prognosis, even after curative resection. Treatment options for pancreatic cancer remain limited, therefore new therapeutic targets are urgently needed. We searched for genes predictive of poor prognosis in pancreatic cancer using a public database and validated the survival impact of the selected gene in a patient cohort., Methods: We used a public database to search for genes associated with early pancreatic cancer recurrence. As a validation cohort, 201 patients who underwent radical resection in our institution were enrolled. Expression of the target gene was evaluated using immunohistochemistry (IHC). We evaluated growth and invasiveness using small interfering RNAs, then performed pathway analysis using gene set enrichment analysis., Results: We extracted ARHGEF2 from GSE21501 as a gene with a high hazard ratio (HR) for early recurrence within 1 year. The high ARHGEF2 expression group had significantly poorer recurrence-free survival (RFS) and poorer overall survival (OS) than the low ARHGEF2 expression group. Multivariate analysis demonstrated that high ARHGEF2 expression was an independent poor prognostic factor for RFS (HR 1.92) and OS (HR 1.63). In vitro, ARHGEF2 suppression resulted in reduced cell growth and invasiveness. Bioinformatic analysis revealed that ARHGEF2 expression was associated with MYC, G2M, E2F, and CDC25A expression, suggesting that c-Myc and cell cycle genes are associated with high ARHGEF2 expression. IHC revealed a positive correlation between ARHGEF2 and c-Myc expression., Conclusions: High ARHGEF2 expression is associated with cell cycle progression, and predicts early recurrence and poor survival in patients with pancreatic cancer.

Background: The clinical significance of programmed death 1 and its ligand (PD-L1) as therapeutic targets has been reported previously. This study aimed to investigate the clinical impact of PD-L1 expression in cancer and stroma cells in cholangiocarcinoma (CCA)., Methods: The study enrolled 177 consecutive CCA patients who underwent curative resection between 2005 and 2014. Expression of PD-L1 in CCA and stroma cells was assayed by immunohistochemistry, and their relationships with patient clinicopathologic characteristics and prognoses were evaluated. Tumor-infiltrating immune cells (CD66b + neutrophils [TANs] and CD163 + M2 macrophages [TAMs]) also were assayed by immunohistochemistry, and their relationship with PD-L1 expression in cancer and stroma cells was evaluated., Results: Among the 177 analyzed CCA cases, PD-L1 expression was identified in cancer cells in 54 cases (30.5%) and in stroma cells in 77 cases (43.5%). The patients with positive PD-L1 expression in cancer and stroma cells had worse overall survival rates than those negative for PD-L1 (cancer cells: hazard ratio [HR] 2.08; P = 0.0004; stroma cells: HR 1.84; P = 0.003). Moreover, the patients with PD-L1-positive cancer cells had higher rates of PD-L1 expression in stroma cells (P < 0.0001) and higher numbers of TANs (P = 0.0003) and TAMs (P = 0.004) than those with low PD-L1 expression. In the multivariate analysis, PD-L1 expression in both cancer and stroma cells (HR 2.20; P = 0.002) was an independent predictor of poor overall survival., Conclusions: The study showed PD-L1 expressed in both CCA and stromal cells and demonstrated that its expression may affect numbers of TANs and TAMs and play a pivotal role in CCA outcomes.

Background: Depletion of skeletal muscle mass (sarcopenia) indicates a poor prognosis for patients with several kinds of cancer, but it remains unclear whether esophageal squamous cell carcinoma (ESCC) is among these cancers. The aim of this study was to clarify the relationship between sarcopenia and postoperative outcome in patients with ESCC treated by esophagectomy., Methods: Skeletal muscle mass was assessed in 138 patients who underwent esophagectomy from August 2009 to May 2014. A multifrequency bioelectrical impedance analysis (InBody 720; Biospace, Tokyo, Japan) was used to assess skeletal muscle mass just before surgery. Postoperative complications were graded according to the Clavien-Dindo classification, and univariate and multivariate analyses were performed for postoperative respiratory complications., Results: Sarcopenia was determined in 61 patients (44.2 %). Preoperative pulmonary function was significantly lower and the rate of respiratory complications significantly higher in the sarcopenia group than in the non-sarcopenia group (p < 0.01). For other complications, the differences were not significant. Multivariate analysis showed that sarcopenia [odds ratio (OR) 5.82; p = 0.0001] and longer operation time (OR 3.09; p = 0.04) were risk factors for the occurrence of respiratory complications., Conclusions: Sarcopenia may be a predictor of pulmonary complications after esophagectomy. Further analysis is needed to clarify whether nutritional intervention improves skeletal muscle mass and thus contributes to reducing postoperative respiratory complications in sarcopenic patients.