KIF23 enhances cell proliferation in pancreatic ductal adenocarcinoma and is a potent therapeutic target.

BACKGROUND: In recent research, high expression of kinesin family member 23 (KIF23), one of the kinesin motor proteins involved in the regulation of cytokinesis, has been shown to be related to poor prognosis in glioma and paclitaxel-resistant gastric cancer, as a results of the enhancement of proliferation, migration, and invasion. In this study, we analyzed the role of KIF23 in the progression of pancreatic ductal adenocarcinoma. METHODS: A bioinformatic method was used to analyze the KIF23 mRNA level in pancreatic tumor tissues compared with normal pancreatic tissues and to analyze the connection between high KIF23 expression and prognosis. We examined the expression of KIF23 using immunohistochemistry and analyzed the connection between the expression of KIF23 and clinicopathological features in pancreatic ductal adenocarcinoma patients. In addition, a colony formation assay, MTT assay, and western blot assay were performed in vitro, along with a mouse xenograft model in vivo, to analyze the effect of KIF23 on proliferation. Further, the correlation between KIF23 and CDCA8 was analyzed by TCGA and immunohistochemical data. RESULTS: Bioinformatic results showed that KIF23 mRNA expression was higher in pancreatic tumor tissues than in normal pancreatic tissues and a poor prognosis has been linked to the high expression of KIF23. Immunohistochemistry revealed that KIF23 was highly expressed at the protein level and high expression of KIF23 correlated with adverse clinicopathological features. Our experimental results demonstrated that knockdown of KIF23 could inhibit the proliferation of pancreatic cells. Further, a positive correlation between KIF23 and CDCA8 expression existed, and KIF23 might promote pancreatic cancer proliferation by affecting CDCA8 expression. CONCLUSIONS: Our data showed that high expression of KIF23 is associated with a poor prognosis, and KIF23 might be a potential therapeutic target for pancreatic ductal adenocarcinoma.

[Factors influencing survival of patients with cancer of the pancreatic head after resection].

OBJECTIVE: The aim of this cohort study was to investigate the clinical outcome and prognostic factors in patients after resection for ductal adenocarcinoma of the pancreatic head. METHODS: patients with pancreatic head cancer undergoing curative resection (R0) between 1997 and 2002 were included in this study. Univariate and multivariate analyses were performed to examine factors affecting clinical outcome and recurrence of the cancer. RESULTS: Surgical procedures consisted of 58 (43.3%) extended pancreaticoduodenectomies (EPD), 47 (35.1%) pancreaticoduodenectomies (PD) and 29 (21.6%) pylorus-preserving pancreaticoduodenectomies (PPPD). The results showed that 81.3% (109/134) of patients had a recurrence during the study period, mainly retroperitoneal combined with distant metastasis (53.7%). The median postoperative survival time was 24.7 months. The 1-, 3- and 5-year overall survival rates for the study population were 67.1%, 38.5% and 17.6%, respectively. Univariate analysis showed that preoperative abdominal and/or back pain, tumor size > 2 cm, lymph node involvement and vascular invasion, and CA19-9 level were all significant predictors for poor survival. Multivariate analysis also showed that preoperative abdominal and/or back pain, tumor size > 2 cm, lymph node involvement and vascular invasion were all significant predictors for poor survival. CONCLUSION: Our results suggest that preoperative abdominal and/or back pain, tumor size > 2 cm, lymph node involvement and vascular invasion are significant predictors for poor survival in patients with pancreatic head cancer.

Integrated analysis of gene expression and copy number variations in MET proto­oncogene­transformed human primary osteoblasts.

The aim of the present study was to screen the potential osteosarcoma (OS)­associated genes and to obtain additional insight into the pathogenesis of OS. Transcriptional profile (ID: GSE28256) and copy number variations (CNV) profile were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) between MET proto­oncogene­transformed human primary osteoblast (MET­HOB) samples and the control samples were identified using the Linear Models for Microarray Data package. Subsequently, CNV areas and CNVs were identified using cut­off criterion of >30%­overlap within the cases using detect_cnv.pl in PennCNV. Genes shared in DEGs and CNVs were obtained and discussed. Additionally, the Database for Annotation, Visualization and Integrated Discovery was used to identify significant Gene Ontology (GO) functions and pathways in DEGs with P<0.05. A total of 1,601 DEGs were screened out in MET­HOBs and compared with control samples, including 784 upregulated genes, such as E2F transcription factor 1 (E2F1) and 2 (E2F2) and 817 downregulated genes, such as retinoblastoma 1 (RB1) and cyclin D1 (CCND1). DEGs were enriched in 344 GO terms, such as extracellular region part and extracellular matrix and 14 pathways, including pathways in cancer and extracellular matrix­receptor interaction. Additionally, 239 duplications and 439 deletions in 678 genes from 1,313 chromosome regions were detected. A total of 12 genes were identified to be CNV­driven genes, including cadherin 18, laminin subunit α 1, spectrin ß, erythrocytic, ciliary rootlet coiled­coil, rootletin pseudogene 2, ß­1,4-N-acetyl-galactosaminyltransferase 1, G protein regulated inducer of neurite outgrowth 1, EH domain binding protein 1­like 1, growth factor independent 1, cathepsin Z, WNK lysine deficient protein kinase 1, glutathione S­transferase mu 2 and microsomal glutathione S­transferase 1. Therefore, cell cycle­associated genes including E2F1, E2F2, RB1 and CCND1, and cell adhesion­associated genes, such as CDH18 and LAMA1 may be used as diagnosis and/or therapeutic markers for patients with OS.

Clinical and Prognostic Significance of Coagulation Assays in Pancreatic Cancer Patients With Absence of Venous Thromboembolism.

OBJECTIVES: Activation of coagulation and fibrinolysis is frequently observed in patients with cancer, even with absence of thrombosis. Furthermore, plasma coagulation parameters were associated with tumor progression, metastasis, and prognosis. Few studies have investigated these associations in pancreatic cancer (PA). This study aimed to investigate the clinical and prognostic significance of various plasma coagulation tests in PA patients with absence of venous thromboembolism (VTE). MATERIALS AND METHODS: A total of 139 PA patients with the absence of VTE were included in the analysis. Patients were followed up for at least 12 months until death. Pretreatment coagulation parameters including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (F), antithrombin-III (AT-III), protein C (PC), factor-VIII (F-VIII), and D-dimer (DD) were evaluated. A total of 40 age-matched and sex-matched healthy individuals without coagulation disorder were enrolled as the control group. RESULTS: Patients were inclined to have higher levels of PT, INR, APTT, F, F-VIII, and DD and lower levels of AT-III and PC than the control group (P<0.01 for all, except P=0.022 for INR and P=0.015 for AT-III). Patients with advanced tumor stages were likely to have higher median DD levels and lower AT-III levels than the control group (P=0.005 and P<0.001, respectively). DD levels were higher in patients with advanced pathology grade (P<0.001). Plasma DD levels (hazards ratio=1.71; 95% confidence interval, 1.07-2.73; P=0.025) were identified as the significantly independent prognostic predictors. CONCLUSIONS: PA patients are susceptible to activation of hemostasis system. Pretreatment plasma DD level was a potential predictor of prognosis in PA patients without VTE.

The outcome of cryoablation in treating advanced pancreatic cancer: a comparison with palliative bypass surgery alone.

OBJECTIVE: This study aimed to investigate the efficacy and safety of palliative bypass surgery combined with cryoablation in treating patients with advanced pancreatic cancer and compare this combination therapy with palliative bypass surgery alone. METHODS: Medical records of 118 patients with advanced pancreatic cancer who received palliative bypass surgery combined with cryoablation (the combination treatment group) or bypass surgery alone (the bypass surgery alone group) at the Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital (Tianjin, China) were retrospectively reviewed. Their baseline and peri-operative parameters were collected and compared. RESULTS: In both groups abdominal distension and pain was significantly ameliorated after treatment. Preoperative jaundice was more common in the bypass surgery group while backache was more frequent in the combination treatment group, which were both relieved by treatment. The pre-operative serum bilirubin level was higher in the bypass surgery group and was decreased significantly after treatment. However, a significant reduction in tumor size and serum carbohydrate antigen 19-9 level was found only in the combination treatment group. There was no significant difference in the incidence of postoperative complications and prognosis between the two groups. CONCLUSIONS: Cryoablation can reduce tumor size and relieve the patients' symptoms and signs such as abdominal discomfort and backache, although it could not improve the patients' prognosis significantly. It is a safe and efficient modality when combined with bypass surgery for patients with advanced pancreatic cancer.