Lung cancer has been the focus of attention for many researchers in recent years for the leading contribution to cancer-related death worldwide, in which lung adenocarcinoma (LUAD) is the most common histological type. However, the potential mechanism behind LUAD initiation and progression remains unclear. Aiming to dissect the tumor microenvironment of LUAD and to discover more informative prognosis signatures, we investigated the immune-related differences in three types of genetic or epigenetic characteristics (expression status, somatic mutation, and DNA methylation) and considered the potential roles that these alterations have in the immune response and both the immune-related metabolic and neural systems by analyzing the multi-omics data from The Cancer Genome Atlas (TCGA) portal. Additionally, a four-step strategy based on lasso regression and Cox regression was used to construct the prognostic prediction model. For the prognostic predictions on the independent test set, the performance of the trained models (average concordance index [C-index] = 0.839) is satisfied, with average 1-year, 3-year, and 5-year areas under the curve (AUCs) equal to 0.796, 0.786, and 0.777. Finally, the overall model was constructed based on all samples, which comprised 27 variables and achieved a high degree of accuracy on the 1-year (AUC = 0.861), 3-year (AUC = 0.850), and 5-year (AUC = 0.916) survival predictions.
Chest wall tumors are a relatively uncommon disease in clinical practice. Most of the published studies about chest wall tumors are usually single-center retrospective studies, involving few patients.Therefore, evidences regarding clinical conclusions about chest wall tumors are lacking, and some controversial issues have still to be agreed upon. In January 2019, 73 experts in thoracic surgery, plastic surgery, science, and engineering jointly released the Chinese Expert Consensus on Chest Wall Tumor Resection and Chest Wall Reconstruction (2018 edition). After that, numerous experts put forward new perspectives on some academic issues in this version of the consensus, pointing out the necessity to further discuss the points of contention. Thus, we conducted a survey through the administration of a questionnaire among 85 experts in the world. Consensus has been reached on some major points as follows. (I) Wide excision should be performed for desmoid tumor (DT) of chest wall. After excluding the distant metastasis by multi-disciplinary team, solitary sternal plasmacytoma can be treated with extensive resection and adjuvant radiotherapy. (II) Wide excision with above 2 cm margin distance should be attempted to obtain R0 resection margin for chest wall tumor unless the tumor involves vital organs or structures, including the great vessels, heart, trachea, joints, and spine. (III) For patients with chest wall tumors undergoing unplanned excision (UE) for the first time, it is necessary to carry out wide excision as soon as possible within 1-3 months following the previous surgery. (IV) Current Tumor Node Metastasis staging criteria (American Joint Committee on Cancer) of bone tumor and soft tissue sarcoma are not suitable for chest wall sarcomas. (V)It is necessary to use rigid implants for chest wall reconstruction once the maximum diameter of the chest wall defect exceeds 5 cm in adults and adolescents. (VI) For non-small cell lung cancer (NSCLC) invading the chest wall, wide excision with neoadjuvant and/or adjuvant therapy are recommended for patients with stage T 3-4 N 0-1 M 0 . As clear guidelines are lacking, these consensus statements on controversial issues on chest wall tumors and resection could possibly serve as further guidance in clinical practice during the upcoming years.
Therapeutic agents that target both tumor cell and vascular endothelial cell may achieve additional anti-tumor efficacy, particularly in lung cancer due to the critical roles of angiogenesis during lung cancer progression and metastasis. In this work, we showed that pitavastatin, a novel cholesterol-lowering drug, potently inhibited lung cancer cells and angiogenesis. This was achieved by the induction of apoptosis and inhibition of proliferation of lung cancer cells and human lung tumor-associated endothelial cell. Pitavastatin was not only effective to chemo-sensitive but also chemo-resistant lung cancer cells. This was also consistent with the finding that pitavastatin significantly enhanced cisplatin’s efficacy in lung cancer xenograft model without causing toxicity in mice. We further showed that pitavastatin inhibited lung tumor angiogenesis in vitro and in vivo through suppressing human lung tumor-associated endothelial cell migration and morphogenesis without affecting adhesion. Mechanistically, we showed that pitavastatin acted on lung cancer cells and human lung tumor-associated endothelial cell through suppressing prenylation-dependent Ras/Raf/MEK and PI3K/Akt/mTOR signaling. Our work is the first to demonstrate the inhibitory effects of pitavastatin on Ras-mediated signaling. Our findings provide pre-clinical evidence to repurpose pitavastatin for the treatment of lung cancer.
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