Hopperdonnelly2592

Background The aim of this study was to identify more accurate variables to improve prognostication of individual patients with colorectal liver metastases (CRLM). Clinicopathological characteristics only partly explain the large range in survival rates. Methods MessengerRNA expression profiles of resected CRLM of two patient groups were analysed by mRNA sequencing poor survivors (death from recurrent disease 60 months after surgery). Tumour and adjacent liver parenchyma samples were analysed. Results MessengerRNA expression profiling of the tumour samples identified 77 genes that were differentially expressed between the two survival groups at a False Discovery Rate (FDR) less then 0.1. In the adjacent liver parenchyma samples only one gene, MTRNR2L1, showed significantly higher expression in the good survivors. Pathway analysis showed higher expression of immune-related and stroma-related genes in tumour samples from good survivors. Expression data was then validated by immunohistochemistry in two cohorts comprising a total of 125 patients. Immunohistochemical markers that showed to be associated with good survival in the total cohort were high K/L+ infiltration in tumour stroma [p = 0.029; OR 2.500 (95% CI 1.100-5.682)] and high CD79A+ infiltration in tumour stroma [p = 0.036; OR 2.428 (95%CI 1.062-5.552)]. Conclusions A high stromal infiltration of CD79A+ B cells and K/L+ plasma cells might be favourable prognostic biomarkers after surgery for CRLM. Copyright © 2020 Hof, Visser, Höppener, Nierop, Terpstra, Gouw, Grünhagen, Verhoef, Sijmons, de Jong and Kok.Background Neoadjuvant chemotherapy (NAC) has been of recent interest as an alternative to upfront surgery followed by adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). However, a subset of patients does not respond to NAC and may have been better managed by upfront surgery. Hence, there is an unmet need for accurate biomarkers for predicting NAC response in PDAC. We aimed to identify upregulated proteins in tumor tissue from poor- and good-NAC responders. Methods Tumor and adjacent pancreas tissue samples were obtained following surgical resection from NAC-treated PDAC patients. SWATH-MS proteomic analysis was performed to identify and quantify proteins in tissue samples. Statistical analysis was performed to identify biomarkers for NAC response. Pathway analysis was performed to characterize affected canonical pathways in good- and poor-NAC responders. Results A total of 3,156 proteins were identified, with 19 being were significantly upregulated in poor-responders compared to good-responders (log2 ratio > 2, p less then 0.05). Those with the greatest ability to predict poor-NAC response were GRP78, CADM1, PGES2, and RUXF. Notably, canonical pathways that were significantly upregulated in good-responders included acute phase signaling and macrophage activation, indicating a heightened immune response in these patients. Conclusion A novel biomarker signature for poor-NAC response in PDAC was identified. Copyright © 2020 Sahni, Nahm, Krisp, Molloy, Mehta, Maloney, Itchins, Pavlakis, Clarke, Chan, Gill, Howell, Samra and Mittal.Ammonium tetrathiomolybdate (ATTM) has been used in breast cancer therapy for copper chelation, as elevated copper promotes tumor growth. ATTM is also an identified H2S donor and endogenous H2S facilitates VitB12-induced S-adenosylmethionine (SAM) generation, which have been confirmed in m6A methylation and lung cancer development. The m6A modification was recently shown to participate in lung adenocarcinoma (LUAD) progression. These conflicting analyses of ATTM's anticancer vs. H2S's carcinogenesis suggest that H2S should not be ignored during LUAD's treatment with ATTM. This study was aimed to explore ATTM's effects on LUAD cells and mechanisms associated with H2S and m6A. It was found that treatment with ATTM inhibited cell growth at high concentrations, while enhanced cell growth at low concentrations in three LUAD cell lines (A549, HCC827, and PC9). However, another copper chelator triethylenetetramine, without H2S releasing activity, was not found to induce cell growth. Low ATTM concentrations also elevctively, H2S impedes ATTM-induced anticancer effects through YTHDF1-dependent PRPF6 m6A methylation in lung adenocarcinoma cells. Copyright © 2020 Li, Li, Huang, Xu, Zheng, Hamsath, Zhang, Dai, Zhang, Wong, Xian, Yang and Liu.MicroRNAs (miRNAs) are a class of small non-coding RNAs which regulate gene expression at post-transcriptional level. Alterations of miR-186 expression were demonstrated in numerous cancers, shown to play a vital role in oncogenesis, invasion, metastasis, apoptosis, and drug resistance. MiR-186 was documented as a tumor suppressor miRNA in the majority of studies, while conflicting reports verified miR-186 as an oncomir. The contradictory role in cancers may impede the application of miR-186, as well as other dual-functional miRNAs, as a diagnostic and therapeutic target. This review emphasizes the alterations and functions of miR-186 in cancers and discusses the mechanisms behind the contradictory findings. Among these, target abundance and dose-dependent effects of miR-186 are highlighted. The paper aims to review the challenges involved in developing diagnostic and therapeutic strategies for cancer treatment based on dual-functional miRNAs. Copyright © 2020 Xiang, Tian, Guan and Niu.Purpose GPSM2 (G protein signaling modulator 2) was reported to be involved in the cell division of breast cancer cells. Additionally, cytoplasmic dynein may mediate the transport process of GPSM2. DYNC1I1 (Cytoplasmic dynein 1 intermediate chain 1) is the most common cargo-binding subunit of dynein. However, the relationship between GPSM2 and DYNC1I1 and its clinical value is unclear. Methods Immunohistochemical staining was performed for assessment of GPSM2 and DYNC1I1 expression. Immunoprecipitation analysis was used to assess the interaction between GPSM2 and DYNC1I1. Results GPSM2 was correlated with clinical characteristics of breast cancer patients and is an unfavorable independent prognostic factor. In addition, nuclear expression of GPSM2 is an unfavorable independent prognostic factor (HR = 2.658, 95% CI = 1.490-4.741, p = 0.001). GPSM2 and DYNC1I1 are known to form a complex in breast cancer cells. Patients who were positive for expression of both DYNC1I1 and GPSM2 presented with shorter recurrence-free survival than other patients. Importantly, patients with GPSM2 nuclear expression showed higher DYNC1I1 expression. Conclusion GPSM2 was an independent prognostic factor in breast cancer and nuclear expression of GPSM2 was significantly associated with poor prognosis, which was related to the positive expression of DYNC1I1. Examination of both GPSM2 and DYNC1I1 is necessary to establish a prognosis in breast cancer patients. Copyright © 2020 Deng, Zhang, Liu, Hou, Che, Qu, Liu, Hu, Zhang and Lv.Background The significance of uncommon epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC) and brain metastasis (BM) remains unclear. Cerebrospinal fluid (CSF) liquid biopsy is a novel tool for assessing EGFR mutations in BM. This study aimed to evaluate the EGFR mutations in patients with NSCLC and newly diagnosed BM and to examine the effect of EGFR tyrosine kinase inhibitors (TKI) on BM harboring CSF-tested uncommon EGFR mutations. Methods This was a prospective study of 21 patients with NSCLC and BM diagnosed between 04/2018 and 01/2019. CSF was obtained to detect the BM EGFR mutations by next-generation sequencing. BM characteristics at magnetic resonance imaging (MRI) and EGFR-TKI response were examined. Results Of 21 patients with NSCLC, 10 (47.6%) had leptomeningeal metastasis (LM), while 11 (52.4%) had brain parenchymal metastasis (BPM); 13 (61.9%) had confirmed EGFR mutation-positive primary tumors. The uncommon mutation rate in CSF ctDNA was 33.3% (7/21). Among those with EGFR mutation-positive primary tumors, the rate of uncommon EGFR mutations in CSF was 53.8% (7/13). Uncommon EGFR mutations were more common in patients with LM than in patients with PBM (6/11, 54.5% vs. 1/10, 10%), and included G719A, L861Q, L703P, and G575R. TKI was effective for four patients with BMs harboring uncommon EGFR mutations. Conclusion In patients with NSCLC and LM, the rate of uncommon EGFR mutation was high. The BMs with uncommon EGFR mutations seem to respond to EGFR-TKI treatment. CSF liquid biopsy could reveal the EGFR genetic profile of the BM and help guide treatment using small-molecule TKI. Copyright © 2020 Ma, Zhang, Tang, Ye, Li, Mu, Li, Liu, Xiang, Huang and Jiang.Natural killer (NK)/T-cell lymphoma (NKTCL) is a subtype of non-Hodgkin lymphoma with aggressive progression and poor prognosis. The molecular mechanisms of NKTCL have not been well-studied. Herein, we revealed the lymphoma-associated dysregulated genes and signaling pathways or biological processes in NKTCL. We characterized that the extracellular matrix (ECM) receptor interaction pathway and T-cell receptor signaling pathway were the main dysregulated pathways in NKTCL by Gene Ontology (GO) analysis and pathway enrichment analysis. By using weighted gene co-expression network analysis (WGCNA), the gene co-expression network of NKTCL (SRP049695) was constructed, and hub genes (LMO3, GRB14) were identified. In addition, another Gene Expression Omnibus (GEO) dataset (GSE69406) was used to validate these hub genes. Furthermore, these hub genes were identified and validated by survival analysis (GSE90597). These results provided novel insights into the pathogenesis of NKTCL. Of particular interest, LMO3 and GRB14 might be potential oncoproteins and biomarkers for the diagnosis and treatment of NKTCL. Copyright © 2020 Liu, Liu, You, Li and Li.Metabolism plays a critical role in direct regulation of a variety of cellular activities via metabolic enzymes and metabolites. Here, we demonstrate that phosphofructokinase 1 platelet isoform (PFKP), which catalyzes a rate-limiting reaction in glycolysis, promotes EGFR activation-induced nuclear translocation and activation of β-catenin, thereby enhancing the expression of its downstream genes CCND1 and MYC in human glioblastoma cells. Importantly, we showed that EGFR-phosphorylated PFKP Y64 has a critical role in AKT activation and AKT-mediated β-catenin S552 phosphorylation and subsequent β-catenin transactivation and promotion of tumor cell glycolysis, migration, invasion, proliferation, and brain tumor growth. These findings highlight a novel mechanism underlying a glycolytic enzyme-mediated β-catenin transactivation and underscore the integrated and reciprocal regulation of metabolism and gene expression, which are two fundamental biological processes in tumor development. Copyright © 2020 Lee, Shao, Ling, Lu, Liu, Du, Chung, Koh, Leem, Shao, Xing, An and Lu.Background Helicobacter pylori (H. pylori) is widely accepted to be the most important cause of gastric non-cardia adenocarcinoma (GNCA), while its role in the development of gastric cardia adenocarcinoma (GCA) is not well-defined. We aimed to investigate current H. pylori infection in relation to the severity of both precancerous and cancerous lesions of the gastric cardia in an Asian population at high risk of GCA. Methods A population-based cross-sectional study was conducted in Linzhou County, Henan Province, China. Two thousand three (2,003) randomly selected participants with data on current H. pylori infection, assayed by 13C-urea breath test (13C-UBT), and a sequence of histological diagnoses of the gastric cardia mucosa were analyzed. Results Of 2,003 subjects, 828 (41.33%) were currently infected with H. CID44216842 pylori. The prevalence of current H. pylori infection increased with increasing severity of histological lesions, from 34.12% in subjects with normal gastric cardia mucosa to 52.17% in subjects with gastric cardia high-grade intraepithelial neoplasia (CHIN)/ gastric cardia adenocarcinoma (GCA) (P for trend less then 0.