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Purpose: To explore the role of FKBP prolyl isomerase 10 (FKBP10) protein in the progression of gastric cancer. Methods: Four independent gastric cancer databases (GSE27342, GSE29272, GSE54129 and TCGA-STAD) were used to identify differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to identify the abnormally active pathways in patients with gastric cancer. Univariate Cox regression analysis was used to identify genes with stable prognostic value in gastric cancer patients based on three independent gastric cancer databases (GSE15459, GSE62254, TCGA-STAD). Gene set enrichment analysis (GSEA) was used to explore the possible pathways related to FKBP10. The reverse transcription-polymerase chain reaction (RT-PCR) was employed to determine the expression of FKBP10 mRNA in the HGC-27 and MKN-7 cell lines. Adhesion assay was used to detect changes in cell adhesion ability. FKBP10, ITGA1, ITGA2, ITGA5, ITGAV, ITGA6, P-AKT473, P-AKT308, AKT, and β-actin were evaluated by Western blot (WB). Results: We first performed differential expression genes (DEGs) screening of four independent GC databases (GSE27342, GSE29272, GSE54129 and TCGA-STAD). Eighty-nine genes showed consistent up-regulation in GC, the results of pathway analysis showed that they were related to "Focal adhesion". The prognostic value of these 89 genes was tested in three independent GC databases GSE15459, GSE62254 and TCGA-STAD cohort. Finally, 12 genes, in which the expression of FKBP10 was prominently increased in patients with lymph node metastasis (LNM), showed stable prognostic value. The following gene set enrichment analysis (GSEA) also showed that FKBP10 is mainly involved in cell adhesion process, while adhesion experiments confirmed that cell adhesion was down-regulated after silencing FKBP10 in GC cells, and adhesion-related molecules integrin αV and α 6 were down-regulated. Conclusion: FKBP10 may be used as a marker for lymph node metastasis of GC and could be used as a potential target for future treatment of GC. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the top five malignant tumors worldwide. At present, the molecular mechanisms of gastric cancer progression are still not completely clear. Cytoplasmic dynein regulates intracellular transport and mitotic spindle localization, and its abnormal function is crucial for tumorigenesis, promotes tumor cell cycle progression, and tumor migration. DYNC1I1 is an important binding subunit of cytoplasmic dynein. However, studies on DYNC1I1 in tumors are currently limited. In the current study, we found that high DYNC1I1 expression in gastric cancer is associated with poor prognosis and is an independent prognostic factor. DYNC1I1 promoted the proliferation and migration of gastric cancer cells both in vitro and in vivo. DYNC1I1 also upregulated IL-6 expression by increasing NF-κB nuclear translocation. Collectively, these data revealed an important role for the DYNC1I1-driven IL-6/STAT pathway in gastric cancer proliferation and migration, suggesting that DYNC1I1 may be a potential therapeutic target for gastric cancer. [ABSTRACT FROM AUTHOR]

Prognostic models are generally used to predict gastric cancer outcomes. However, no model combining patient-, tumor- and host-related factors has been established to predict outcomes after radical gastrectomy, especially outcomes of patients without nodal involvement. The aim of this study was to develop a prognostic model based on the systemic inflammatory response and clinicopathological factors of resectable gastric cancer and determine whether the model can improve prognostic accuracy in node-negative patients. We reviewed the clinical, laboratory, histopathological and survival data of 1397 patients who underwent radical gastrectomy between 2007 and 2013. Patients were split into development and validation sets of 1123 and 274 patients, respectively. Among all 1397 patients, 545 had node-negative gastric cancer; 440 were included in the development set, 105 were included in the validation set. A prognostic model was constructed from the development set. The scoring system was based on hazard ratios in a Cox proportional hazard model. In the multivariate analysis, age, tumor size, Lauren type, depth of invasion, lymph node metastasis, and the neutrophil—lymphocyte ratio were independent prognostic indicators of overall survival. A prognostic model was then established based on the significant factors. Patients were categorized into five groups according to their scores. The 3-year survival rates for the low- to high-risk groups were 98.9%, 92.8%, 82.4%, 58.4%, and 36.9%, respectively (P < 0.001). The prognostic model clearly discriminated patients with stage pT1-4N0M0 tumor into four risk groups with significant differences in the 3-year survival rates (P < 0.001). Compared with the pathological T stage, the model improved the predictive accuracy of the 3-year survival rate by 5% for node-negative patients. The prognostic scores also stratified the patients with stage pT4aN0M0 tumor into significantly different risk groups (P = 0.004). Furthermore, the predictive value of this model was validated in an independent set of 274 patients. This model, which included the systemic inflammatory markers and clinicopathological factors, is more effective in predicting the prognosis of node-negative gastric cancer than traditional staging systems. Patients in the high-risk group might be good candidates for adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Although much progress has been made in chemotherapy or target therapy for advanced gastric cancer, the prognosis is still poor. It is necessary to screen biomarkers for early diagnosis and prognosis prediction. However, the prognostic value of LOX family in gastric cancer and the underlying molecular mechanisms for promoting the progression of gastric cancer remains unclear. Among five members of LOX family, LOXL1 was the unique independent prognostic risk factor. The nomogram established based on the expression of LOXL1 and other clinical parameters could predict the overall survival rate of gastric cancer. Knockdown (KD) of LOXL1 decreased cell proliferation and led to G1 phase arrest in gastric cells. According to GSEA analysis that LOXL1 was positively correlated with the WNT signaling pathway, in vitro experiment proved that LOXL1-KD reduced the phosphorylation level of β-catenin and the expression of the downstream G1 phase checkpoint CCND1. In conclusion, LOXL1 has been identified as a potential risk prognostic biomarker for gastric cancer by promoting gastric cancer proliferation via WNT/β-catenin/cyclinD1 pathway. • LOXL1 is the only independent prognostic risk factor in GC among all of LOX family members. • We construct a nomogram model based on LOXL1 expression. • LOXL1 leads to poor prognosis by promoting GC cell proliferation via WNT/β-catenin/cyclin D1 pathway. [ABSTRACT FROM AUTHOR]