Comprehensive analysis of the transcriptional expressions and prognostic value of S100A family in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a treatment-refractory malignancy with poor prognosis. It is urgent to identify novel and valid biomarkers to predict the progress and prognosis of PDAC. The S100A family have been identified as being involved in cell proliferation, migration and differentiation progression of various cancer types. However, the expression patterns and prognostic values of S100As in PDAC remain to be analyzed. METHODS: We investigated the transcriptional expressions, methylation level and prognostic value of S100As in PDAC patients from the Oncomine, GEPIA2, Linkedomics and cBioPortal databases. Real-time PCR was used to detect the expressions of S100A2/4/6/10/14/16 in four pancreatic cancer cell lines and pancreatic cancer tissues from PDAC patients undergoing surgery. To verify the results further, immunohistochemistry was used to measure the expression of S100A2/4/6/10/14/16 in 43 PDAC patients' tissue samples. The drug relations of S100As were analyzed by using the Drugbank database. RESULTS: The results suggested that, the expression levels of S100A2/4/6/10/14/16 were elevated to PDAC tissues than in normal pancreatic tissues, and the promoter methylation levels of S100A S100A2/4/6/10/14/16 in PDAC (n = 10) were lower compared with normal tissue (n = 184) (P < 0.05). In addition, their expressions were negatively correlated with PDAC patient survival. CONCLUSIONS: Taken together, these results suggest that S100A2/4/6/10/14/16 might be served as prognostic biomarkers for survivals of PDAC patients.

Effect of KIF22 on promoting proliferation and migration of gastric cancer cells via MAPK-ERK pathways.

BACKGROUND: Gastric cancer (GC) is one of the most globally prevalent cancers in the world. The pathogenesis of GC has not been fully elucidated, and there still lacks effective targeted therapeutics. The influence of altered kinesin superfamily protein 22 (KIF22) expression in GC progression is still unclearly. The aim of this study was to investigate the KIF22 effects on GC and related mechanisms. METHODS: Gastric carcinoma tissues and matching non-cancerous tissues were collected from patients with GC who have accepted a radical gastrectomy in Lanzhou University Second Hospital from May 2013 to December 2014. The expression of KIF22 was examined in GC of 67 patients and 20 para-carcinoma tissues by immunochemical staining. The relationship between the expression of KIF22 and clinicopathologic characteristics was next investigated in the remaining 52 patients except for 15 patients who did not complete follow-up for 5 years. Cell viability was performed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test and colony formation assay in the MGC-803 and BGC-823 GC cells. Cell scratch and trans-well invasion assay was performed to assess migration ability in the MGC-803 and BGC-823 GC cells. Gene set enrichment analysis (GSEA) pathway enrichment analysis was performed to explore the potential functions. Cell cycle was detected by flow cytometry. In addition, the two GC cell lines were used to elucidate the underlying mechanism of KIF22 in GC in vitro via assessing the effects on mitogen-activated protein kinase and extracellular regulated protein kinases (MAPK/ERK) signal transduction pathway-related expressions by Western blotting assays. The differences were compared by t tests, one-way analysis of variance, and Chi-squared tests. RESULTS: The study showed that KIF22 was up-regulated in GC, and KIF22 high expression was significantly related to differentiation degree (χ = 12.842, P = 0.002) and poorly overall survivals. GSEA pathway enrichment analysis showed that KIF22 was correlated with the cell cycle. Silence of KIF22 decreased the ability of the proliferation and migration in gastric cells, induced G1/S phase cell cycle arrest via regulating the MAPK-ERK pathways. CONCLUSIONS: KIF22 protein level was negatively correlated with prognosis. KIF22 knockdown might inhibit proliferation and metastasis of GC cells via the MAPK-ERK signaling pathway.

The Role of Shcbp1 in Signaling and Disease.

Src homolog and collagen homolog (Shc) proteins have been identified as adapter proteins associated with cell surface receptors and have been shown to play important roles in signaling and disease. Shcbp1 acts as a Shc SH2-domain binding protein 1 and is involved in the regulation of signaling pathways, such as FGF, NF-κB, MAPK/ERK, PI3K/AKT, TGF-ß1/Smad and ß -catenin signaling. Shcbp1 participates in T cell development, the regulation of downstream signal transduction pathways, and cytokinesis during mitosis and meiosis. In addition, Shcbp1 has been demonstrated to correlate with Burkitt-like lymphoma, breast cancer, lung cancer, gliomas, synovial sarcoma, human hepatocellular carcinoma and other diseases. Shcbp1 may play an important role in tumorigenesis and progression. Accordingly, recent studies are reviewed herein to discuss and interpret the role of Shcbp1 in normal cell proliferation and differentiation, tumorigenesis and progression, as well as its interactions with proteins.