Background ANLN has been identified as an actin‐binding protein and previous studies have suggested that ANLN is associated with actin cytoskeletal dynamics. Lung adenocarcinoma is a poor prognosis tumor. Metastasis is a very common complication and is regarded as the main cause for an unsatisfactory treatment outcome. Whether ANLN is involved in the metastasis of lung adenocarcinoma is unknown. Methods We performed immunohistochemical staining and analyzed the correlation between the expression level and pathological parameters. We tested the migration and invasion of A549 and PC9 cell after interference with ANLN expression by Transwell and scratch wound healing assays. Protein expression of E‐cadherin, vimentin and N‐cadherin were detected using Western blotting and immunofluorescence staining. The same experiment was also tested after overexpression of ANLN. Results The metastasis of patients with high expression of ANLN was significantly more than that of patients with low expression of ANLN. In vitro, after interfering with ANLN expression, E‐cadherin and vimentin expression were increased and N‐cadherin expression was decreased in A549 and PC9 cells. Migration and invasion ability of A549 and PC9 cells were decreased,vice versa. Conclusion Our study suggests that the expression of ANLN in lung adenocarcinoma is associated with metastasis of cancer cells. ANLN may be involved in the metastasis of lung adenocarcinoma by promoting epithelial mesenchymal transformation of tumor cells.

BackgroundThe purpose of the study was to investigate the association between radiomic features based on contrast‐enhanced multidetector computed tomography (CT) and the Ki‐67 proliferation index (PI) in patients with lung cancer.MethodsOne hundred and ten patients with lung cancer confirmed by surgical histology were retrospectively included. Radiomic features were extracted from preoperative contrast‐enhanced chest multidetector CT images for each tumor using open‐source three‐dimensional Slicer software. Statistical analysis was performed to determine significant radiomic features serving as image predictors of Ki‐67 status in lung cancer and to investigate the relationship between these features and Ki‐67 PI.ResultsHigher Ki‐67 expression was more common in men (P = 0.02) and patients with a smoking history (P = 0.01). Twelve radiomic features were significantly associated with Ki‐67 status. Multivariate logistic regression analysis identified inverse variance, minor axis, and elongation as independent predictors of Ki‐67 PI. There was a positive correlation between inverse variance, minor axis, elongation (P = 0.00, P = 0.02, and P = 0.14, respectively) and Ki‐67 PI. The area under the curve to identify high Ki‐67 status for inverse variance was 0.77 with a cutoff value of 0.47, which was significantly higher than for minor axis and elongation (P = 0.02 and P = 0.03, respectively).ConclusionRadiomic features based on contrast CT images, including inverse variance, minor axis, and elongation, can serve as noninvasive predictors of Ki‐67 status in patients with lung cancer. Inverse variance could be superior to the other radiomic features to identify high Ki‐67 status.

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Forkhead box protein M1 (FOXM1) was identified as an oncogenic transcription factor and master regulator of tumor progression and metastasis. FOXM1 expression often correlates with poor prognosis and chemotherapy resistance. In the present study, we investigated the association of FOXM1 expression and chemoresistance in pancreatic cancer. Elevated FOXM1 protein levels were associated with gemcitabine chemoresistance in patients with pancreatic cancer. In gemcitabine resistance cell line models of pancreatic cancer, FOXM1 expression increased, which induced gemcitabine chemoresistance in vitro. In pancreatic cancer cells treated with gemcitabine, FOXM1 affected nuclear factor κB (NF-κB) signaling activity. Immunohistochemical analysis demonstrated a negative association of FOXM1 expression and the level of phosphorylated signal transducer and activator of transcription 1 (pSTAT1) in human pancreatic cancer tissues. Dual-luciferase reporter assays and chromatin-immunoprecipitation assays demonstrated that pSTAT1 directly binds to the FOXM1 promoter to down-regulate its transcription. Interferon γ (IFNγ) promoted gemcitabine-induced cell apoptosis and inhibited cell proliferation in vitro and in vivo by FOXM1 inhibition. These data suggested that FOXM1 enhances chemoresistance to gemcitabine in pancreatic cancer. IFNγ could be used to down-regulate the expression of FOXM1 through STAT1 phosphorylation, thereby increasing the sensitivity of pancreatic cancer cells to gemcitabine. These studies suggested the sensitization by IFNγ in pancreatic ductal adenocarcinoma (PDAC) chemotherapy, which requires further clinical studies.

Background: The purpose of this study was to explore the reason for guanine nucleotide binding-protein gamma subunit-4 (GNG4) overexpression and the relationship between GNG4 overexpression and the poor prognosis of lung adenocarcinoma (LUAD) patients. Methods: The genes and phenotypes related to GNG4 expression in patients with lung adenocarcinoma were analyzed by bioinformatics. The phenotype indicated by bioinformatic analysis was confirmed by experiments. Results: GNG4 expression is elevated in lung adenocarcinoma, and overexpressed GNG4 is related to the poor prognosis of patients with lung adenocarcinoma. The hypoxic microenvironment of lung adenocarcinoma can promote GNG4 expression and GNG4 promotes the migration and proliferation of lung adenocarcinoma cells. Conclusions: GNG4 expression in lung adenocarcinoma was significantly higher than in paired adjacent tissues. GNG4 overexpression is associated with a variety of malignant phenotypes of lung adenocarcinoma. Increased GNG4 expression is related to the hypoxic microenvironment in lung adenocarcinoma.

ObjectivePancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumour with limited treatment options. Here, we identified syndecan binding protein (SDCBP), also known as syntenin1, as a novel targetable factor in promoting PDAC tumour progression. We also explored a therapeutic strategy for suppressing SDCBP expression.DesignWe used samples from patients with PDAC, human organoid models, LSL-KrasG12D/+mice, LSL-Trp53R172H/+ and Pdx1-Cre (KPC) mouse models, and PDX mouse models. Immunostaining, colony formation assay, ethynyl-2-deoxyuridine incorporation assay, real-time cell analysis, cell apoptosis assay, automated cell tracking, invadopodia detection and gelatin degradation assays, coimmunoprecipitation, and pull-down assays were performed in this study.ResultsThe median overall survival and recurrence-free survival rates in the high-SDCBP group were significantly shorter than those in the low-SDCBP group. In vitro and in vivo studies have demonstrated that SDCBP promotes PDAC proliferation and metastasis. Mechanically, SDCBP inhibits CK1δ/ε-mediated YAP-S384/S387 phosphorylation, which further suppresses β-TrCP-mediated YAP1 ubiquitination and proteasome degradation by directly interacting with YAP1. SDCBP interacts with the TAD domain of YAP1, mainly through its PDZ1 domain. Preclinical KPC mouse cohorts demonstrated that zinc pyrithione (ZnPT) suppresses PDAC tumour progression by suppressing SDCBP.ConclusionsSDCBP promotes the proliferation and metastasis of PDAC by preventing YAP1 from β-TrCP-mediated proteasomal degradation. Therefore, ZnPT could be a promising therapeutic strategy to inhibit PDAC progression by suppressing SDCBP.

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Pancreatic cancer is a dismal malignancy with poor prognosis. In spite of progress in surgical technology, chemotherapy is still the cornerstone in the multi-disciplinary treatment. Albumin-bound paclitaxel is a first-line treatment for PDAC patients. Yet the response rate of the drug is far from satisfying. SOX8 is a member of the sex determining region Y-boxes family, which is potentially related to the chemoresistance of tumor. Patient with high expression of SOX8 were insensitive to albumin-bound paclitaxel. SOX8 reduced apoptosis and G2/M cell cycle arrest caused by albumin-bound paclitaxel. SOX8 transcriptionally regulated EZH2, which reduced expression of SPARC by promoting the methylation of SPARC, thereby reducing the transport of albumin-bound paclitaxel in pancreatic cancer cells. EZH2 inhibitor, UNC1999, can reverse the effect of SOX8 on chemo-resistance of albumin-bound paclitaxel. Collectively, our data revealed SOX8/EZH2/SPARC signaling induced primary chemo-resistance of albumin-bound paclitaxel in pancreatic ductal adenocarcinoma.