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Background: Accumulating evidence indicates tumor-promoting roles of synaptotagmin 13 (SYT13) in several cancers; however, no studies have investigated its expression in breast cancer (BC). This study aimed to clarify the significance of SYT13 in BC. Methods: SYT13 mRNA expression levels were evaluated in BC cell lines. Polymerase chain reaction (PCR) array analysis was conducted to determine the correlation between expression levels of SYT13 and other tumor-associated genes. Then, the association of SYT13 expression levels in the clinical BC specimens with patients’ clinicopathological factors was evaluated. These findings were subsequently validated using The Cancer Genome Atlas (TCGA) database. Results: Among 13 BC cell lines, estrogen receptor (ER)-positive cells showed higher SYT13 mRNA levels than ER-negative cells. PCR array analysis revealed positive correlations between SYT13 and several oncogenes predominantly expressed in ER-positive BC, such as estrogen receptor 1, AKT serine/threonine kinase 1, and cyclin-dependent kinases 4. In 165 patients, ER-positive specimens exhibited higher SYT13 mRNA expression levels than ER-negative specimens. The TCGA database analysis confirmed that patients with ER-positive BC expressed higher SYT13 levels than ER-negative patients. Conclusion: This study suggests that SYT13 is highly expressed in ER-positive BC cells and clinical specimens, and there is a positive association of SYT13 with the ER signaling pathways. [ABSTRACT FROM AUTHOR]

Background Hepatocellular carcinoma (HCC) is one of the top five causes of cancer-related deaths worldwide. We developed a novel technique to identify cancer-related genes of HCC as follows: triple-combination array analysis, which combines gene expression profiles, single nucleotide polymorphism arrays, and methylation arrays. Materials and methods Triple-combination array analysis was performed on one HCC sample from a 68-y-old female patient, and one candidate cancer-related gene was selected. Subsequently, we analyzed the identified gene by quantitative real-time reverse-transcriptase polymerase chain reaction (PCR) and methylation-specific PCR in nine HCC cell lines and in samples from 48 HCC patients. Additionally, we evaluated gene expression by immunohistochemistry and Western blotting. Results Using this method, protein tyrosine kinase 7 ( PTK7 ) was detected as a candidate cancer-related gene. PTK7 was revealed to be hypermethylated (methylation value 0.826, range 0–1.0) in cancer tissue, compared with that of adjacent noncancerous tissues (0.047) by methylation array. Of the 48 clinical samples, 30 HCC samples (62.5%) showed PTK7 promoter hypermethylation. Downregulation of PTK7 (expressions in tumor tissues decreased by ≥50% compared with the noncancerous tissues) was significantly associated with age >60 y ( P = 0.030) and elevation in serum protein induced by vitamin K absence or antagonists-II ( P = 0.033). Moreover, patients with downregulation were significantly inferior in overall survival ( P < 0.001) than the others. [ABSTRACT FROM AUTHOR]

Aim: To identify simple and sensitive markers for postoperative complications after gastrectomy, the predictive values were compared among candidate preoperative factors., Methods: Three-hundred and twelve patients with previously untreated clinical T2-4 gastric cancer who underwent a D2 standard gastrectomy (distal gastrectomy or total gastrectomy) were included in the analysis. Correlations between 21 parameters that can be determined by preoperative routine blood tests and clinically relevant postoperative complications (grade II or higher according to the Clavien-Dindo classification) were evaluated. The optimal cutoff values and clinical significance of the selected markers were further evaluated by subgroup analyses according to age, body mass index, operative procedure and clinical disease stage., Results: Sixty-six patients (21.1%) experienced grade II or higher postoperative complications. The platelet-lymphocyte ratio (PLR, total lymphocyte count/platelet count × 100) exhibited the highest area under the curve value (0.639) for predicting postoperative complications among the 21 parameters, and the optimal cutoff value was determined to be 0.71 (sensitivity = 70%, specificity = 56%). In the univariate analysis, the odds ratio of a low PLR for the occurrence of postoperative complications was 2.94 (95%CI: 1.66-5.35, P < 0.001), and a multivariate binomial logistic analysis involving other potential risk factors identified a low PLR as an independent risk factor for postoperative complications (OR = 3.32, 95%CI: 1.82-6.25, P < 0.001). In subgroups classified according to age, body mass index, operative procedure and clinical disease stage, the low PLR group exhibited an increased incidence of postoperative complications., Conclusion: The preoperative PLR is a simple and useful predictor of complications after curative gastrectomy in patients with clinical T2-4 gastric cancer., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest.

Peritoneal dissemination represents a devastating form of gastric cancer (GC) progression with a dismal prognosis. There is no effective therapy for this condition. The 5-year survival rate of patients with peritoneal dissemination is 2%, even including patients with only microscopic free cancer cells without macroscopic peritoneal nodules. The mechanism of peritoneal dissemination of GC involves several steps: detachment of cancer cells from the primary tumor, survival in the free abdominal cavity, attachment to the distant peritoneum, invasion into the subperitoneal space and proliferation with angiogenesis. These steps are not mutually exclusive, and combinations of different molecular mechanisms can occur in each process of peritoneal dissemination. A comprehensive understanding of the molecular events involved in peritoneal dissemination is important and should be systematically pursued. It is crucial to identify novel strategies for the prevention of this condition and for identification of markers of prognosis and the development of molecular-targeted therapies. In this review, we provide an overview of recently published articles addressing the molecular mechanisms of peritoneal dissemination of GC to provide an update on what is currently known in this field and to propose novel promising candidates for use in diagnosis and as therapeutic targets.

Hepatocellular carcinoma (HCC) is a primary cancer of the liver that is predominant in developing countries and is responsible for nearly 600000 deaths each year worldwide. Similar to many other tumors, the development of HCC must be understood as a multistep process involving the accumulation of genetic and epigenetic alterations in regulatory genes, leading to the activation of oncogenes and the inactivation or loss of tumor suppressor genes. Extensive research over the past decade has identified a number of molecular biomarkers, including aberrant expression of HCC-related genes and microRNAs. The challenge facing HCC research and clinical care at this time is to address the heterogeneity and complexity of these genetic and epigenetic alterations and to use this information to direct rational diagnosis and treatment strategies. The multikinase inhibitor sorafenib was the first molecularly targeted drug for HCC to show some extent of survival benefits in patients with advanced tumors. Although the results obtained using sorafenib support the importance of molecular therapies in the treatment of HCC, there is still room for improvement. In addition, no molecular markers for drug sensitivity, recurrence and prognosis are currently clinically available. In this review, we provide an overview of recently published articles addressing HCC-related genes and microRNAs to update what is currently known regarding genetic and epigenetic aspects of the pathogenesis of HCC and propose novel promising candidates for use as diagnostic and therapeutic targets in HCC.

Gastric cancer (GC) is the third most common cause of cancer-related death in the world, representing a major global health issue. Although the incidence of GC is declining, the outcomes for GC patients remain dismal because of the lack of effective biomarkers to detect early GC and predict both recurrence and chemosensitivity. Current tumor markers for GC, including serum carcinoembryonic antigen and carbohydrate antigen 19-9, are not ideal due to their relatively low sensitivity and specificity. Recent improvements in molecular techniques are better able to identify aberrant expression of GC-related molecules, including oncogenes, tumor suppressor genes, microRNAs and long non-coding RNAs, and DNA methylation, as novel molecular markers, although the molecular pathogenesis of GC is complicated by tumor heterogeneity. Detection of genetic and epigenetic alterations from gastric tissue or blood samples has diagnostic value in the management of GC. There are high expectations for molecular markers that can be used as new screening tools for early detection of GC as well as for patient stratification towards personalized treatment of GC through prediction of prognosis and drug-sensitivity. In this review, the studies of potential molecular biomarkers for GC that have been reported in the publicly available literature between 2012 and 2015 are reviewed and summarized, and certain highlighted papers are examined.

Aim: To identify sensitive predictors of clinically relevant postoperative pancreatic fistula (POPF) at the acute phase after pancreatectomy., Methods: This study included 153 patients diagnosed as having POPFs at postoperative day (POD) 3 after either open pancreatoduodenectomy or distal pancreatectomy between January 2008 and March 2013. The POPFs were categorized into three grades based on the International Study Group on Pancreatic Fistula Definition, and POPFs of grades B or C were considered to be clinically relevant. The predictive performance for the clinically relevant POPF formation of values at PODs 1, 3 and 5 as well as time-dependent changes in levels of inflammatory markers, including white blood cell count, neutrophil count, total lymphocyte count, C-reactive protein (CRP), procalcitonin level, platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio, and amylase content in the drain fluid were compared using the receiver operating characteristic (ROC) curve and multivariable analyses. A scoring system for the prediction of clinically relevant POPFs was created using five risk factors identified in this study, and its diagnostic performance was also evaluated., Results: Over time, 77 (50%) of 153 enrolled patients followed a protracted course and were categorized as having clinically relevant POPFs. ROC curve analyses revealed that changes in CRP levels from POD 1 to POD 3 had the greatest area under the curve value (0.767) and that an elevated CRP level of 28.4 mg/L yielded the most optimal predictive value for clinically relevant POPFs. Multivariable analyses for the risk factors of clinically relevant POPFs identified invasive carcinomas of the pancreas and elevation of the CRP level (≥ 28.4 mg/L, from POD 1 to POD 3) as independent diagnostic factors for clinically relevant POPFs (OR 2.94, 95%CI: 1.08-8.55, P = 0.035 and OR 4.82, 95%CI: 1.25-20.2, P = 0.022, respectively). A gradual increase in the prevalence of clinically relevant POPFs in proportion to the risk classification score was confirmed. A highly elevated CRP level and a risk score ≥ 8 were significantly associated with a prolonged duration of drain placement and postoperative hospitalization., Conclusion: A steep rise in the serum CRP level from POD 1 to POD 3 was a highly predictive factor for subsequent clinically relevant POPFs.