The enigmatic helicase DHX9 as a candidate prognostic biomarker for resected pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, and current therapies have limited efficacy on PDAC. The DEAH-box helicase 9 (DHX9) is widely reported to influence cell biological behavior via regulating DNA replication, genomic stability, transcription, translation, and microRNA biogenesis. However, the prognostic role of DHX9 in PDAC remains unclear. Thus, the objective of this study is to investigate the prognostic value of DHX9 expression in PDAC patients. Methods: Tumor specimens from PDAC patients with surgical resection were obtained, and DHX9 was stained and analyzed in this study. Univariate and multivariate Cox regression analyses were utilized to identify independent risk factors of overall survival (OS) and recurrence-free survival (RFS). The prognostic nomograms for predicting OS and RFS were established to obtain superior predictive power. Results: Among the enrolled 110 patients, 61 patients were identified as having high expression of DHX9. The correlation analysis revealed that higher DHX9 expression in PDAC was prone to have advanced N stage (p = 0.010) and TNM stage (p = 0.017). For survival, the median OS (21.0 vs. 42.0 months, p < 0.001) and RFS (12.0 vs. 24.0 months, p < 0.001) of patients in the high DHX9 group were significantly shorter than those in the low DHX9 group. Within the univariate and multivariate analyses, American Joint Committee on Cancer (AJCC) N stage (p = 0.036) and DHX9 expression (p = 0.041) were confirmed as independent prognostic factors of OS, while nerve invasion (p = 0.031) and DHX9 expression (p = 0.005) were independent prognostic factors of RFS. Finally, the novel prognostic nomograms for OS and RFS were established and showed superior predictive accuracy. Conclusion: This study identified the independent prognostic value of DHX9 for RFS and OS in resected PDAC patients, and higher DHX9 expression was prone to have an earlier recurrence and shorter OS. Therefore, DHX9 may be a promising and valuable biomarker and a potential target for treating PDAC. More accurate and promising predictive models would be achieved when DHX9 is incorporated into nomograms.

Effect of World Health Organization (WHO) Histological Classification on Predicting Lymph Node Metastasis and Recurrence in Early Gastric Cancer.

BACKGROUND The World Health Organization (WHO) histological classification for gastric cancer is widely accepted and used. However, its impact on predicting lymph node metastasis and recurrence in early gastric cancer (EGC) is not well studied. MATERIAL AND METHODS From 1987 to 2005, 2873 EGC patients with known WHO histological type who had undergone curative resection were enrolled in this study. In all, 637 well-differentiated adenocarcinomas (WD), 802 moderately-differentiated adenocarcinomas (MD), 689 poorly-differentiated adenocarcinomas (PD), and 745 signet-ring cell adenocarcinomas (SRC) were identified. RESULTS The distribution of demographic and clinical features in early gastric cancer among WD, MD, PD, and SRC were significantly different. Lymph node metastasis was observed in 317 patients (11.0%), with the lymph node metastasis rate being 5.3%, 14.8%, 17.0%, and 6.3% in WD, MD, PD, and SRC, respectively. Univariate and multivariate analyses indicated that gender, tumor size, gross appearance, depth of invasion, and WHO classification were significantly associated with lymph node metastasis. Recurrence was observed in 83 patients (2.9%), with the recurrence rate being 2.2%, 4.5%, 3.0%, and 1.6% in WD, MD, PD, and SRC, respectively. Multivariate analysis confirmed that MD, elevated gross type, and lymph node metastasis were independent risk factors for recurrence in EGC. MD patients showed worse disease-free survival than non-MD patients (P=0.001). CONCLUSIONS WHO classification is useful and necessary to evaluate during the perioperative management of EGC. Treatment strategies for EGC should be made prudently according to WHO classification, especially for MD patients.

Ferulic Acid Exerts Anti-Angiogenic and Anti-Tumor Activity by Targeting Fibroblast Growth Factor Receptor 1-Mediated Angiogenesis.

Most anti-angiogenic therapies currently being evaluated target the vascular endothelial growth factor (VEGF) pathway; however, the tumor vasculature can acquire resistance to VEGF-targeted therapy by shifting to other angiogenesis mechanisms. Therefore, other therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated. Here, we identified ferulic acid as a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor and a novel agent with potential anti-angiogenic and anti-cancer activities. Ferulic acid demonstrated inhibition of endothelial cell proliferation, migration and tube formation in response to basic fibroblast growth factor 1 (FGF1). In ex vivo and in vivo angiogenesis assays, ferulic acid suppressed FGF1-induced microvessel sprouting of rat aortic rings and angiogenesis. To understand the underlying molecular basis, we examined the effects of ferulic acid on different molecular components and found that ferulic acid suppressed FGF1-triggered activation of FGFR1 and phosphatidyl inositol 3-kinase (PI3K)-protein kinase B (Akt) signaling. Moreover, ferulic acid directly inhibited proliferation and blocked the PI3K-Akt pathway in melanoma cell. In vivo, using a melanoma xenograft model, ferulic acid showed growth-inhibitory activity associated with inhibition of angiogenesis. Taken together, our results indicate that ferulic acid targets the FGFR1-mediated PI3K-Akt signaling pathway, leading to the suppression of melanoma growth and angiogenesis.