Purpose:
Examining the role of developmental signaling pathways in “driver gene–negative” lung adenocarcinoma (patients with lung adenocarcinoma negative for EGFR, KRAS, BRAF, HER2, MET, ALK, RET, and ROS1 were identified as “driver gene–negative”) may shed light on the clinical research and treatment for this lung adenocarcinoma subgroup. We aimed to investigate whether developmental signaling pathways activation can stratify the risk of “driver gene–negative” lung adenocarcinoma.
Experimental Design:
In the discovery phase, we profiled the mRNA expression of each candidate gene using genome-wide microarrays in 52 paired lung adenocarcinoma and adjacent normal tissues. In the training phase, tissue microarrays and LASSO Cox regression analysis were applied to further screen candidate molecules in 189 patients, and we developed a predictive signature. In the validation phase, one internal cohort and two external cohorts were used to validate our novel prognostic signature.
Results:
Kyoto Encyclopedia of Genes and Genomes pathway analysis based on whole-genome microarrays indicated that the Wnt/β-catenin pathway was activated in “driver gene–negative” lung adenocarcinoma. Furthermore, the Wnt/β-catenin pathway–based gene expression profiles revealed 39 transcripts differentially expressed. Finally, a Wnt/β-catenin pathway–based CSDW signature comprising 4 genes (CTNNB1 or β-catenin, SOX9, DVL3, and Wnt2b) was developed to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter overall survival [HR, 10.42; 6.46–16.79; P < 0.001) than patients with low-risk scores.
Conclusions:
The CSDW signature is a reliable prognostic tool and may represent genes that are potential drug targets for “driver gene–negative” lung adenocarcinoma.
Lung cancer is the leading cause of mortality among malignant diseases in humans worldwide. During the last decade, molecular targeted therapies for non-small cell lung cancer using first-generation, reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib, have been shown to be a promising approach for patients harboring activating mutations in EGFR. The current study reports a 77-year-old patient diagnosed with adenocarcinoma harboring L858R and T790M point mutations in the EGFR gene. The patient was treated with gefitinib as the second-line therapy, but no clinical benefit was observed. As the majority of patients with lung cancer receiving EGFR-TKI therapy acquire resistance, repeated biopsies and detection of the EGFR mutation state are beneficial for selecting appropriate treatments.
Differentially expressed genes in peripheral blood mononuclear cells between CHB and ASC have been isolated by suppression subtractive hybridization, including some new genes. Of the up-regulated genes in CHB, most are known to be responsive to inflammatory conditions. These genes might provide clues in elucidating the mechanisms of the two different HBV infection states and designing therapeutic targets for HBV infection.
The main shortcomings of the software-based power engineering education are a lack of physical understanding of phenomena and hands-on experience. Existing scaled-down analogous educational power system platforms cannot be widely used for experiments in universities due to the high cost, complicated operation, and huge size. An integrated power distribution system laboratory platform (PDSLP) using modular miniature physical elements is proposed in this paper. The printed circuit board (PCB) and microelectronic technology are proposed to construct each physical element. Furthermore, the constructed physical elements are used to set up an integrated PDSLP based on modular assembly technology. The size of the proposed cost-efficient PDSLP is significantly reduced, and the reliability of the proposed PDSLP can be improved greatly because the signal transmission path is shortened and a number of welding points are reduced. A PDSLP for fault location in neutral non-effectively grounded distribution systems (NGDSs) is selected as a typical experimental scenario and one scaled-down distribution network with three feeders is subsequently implemented and discussed. The measured zero-sequence currents by our proposed PDSLP when a single-phase earth fault occurred can reveal the true features of the fault-generated signals, including steady-state and transient characteristics of zero-sequence currents. They can be readily observed and used for students to design corresponding fault location algorithms. Modular renewable energy sources and other elements can be designed, implemented and integrated into the proposed platform for the laboratory education of the active distribution networks in the future.
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