Virtual bronchoscopic navigation with intraoperative cone-beam CT for the diagnosis of peripheral pulmonary nodules.

OBJECTIVE: Transbronchial biopsy is a safe manner with fewer complications than percutaneous transthoracic needle biopsy; however, the current diagnostic yield is still necessitating further improvement. We aimed to evaluate the diagnostic yield of using virtual bronchoscopic navigation (VBN) and cone-beam CT (CBCT) for transbronchial biopsy and to investigate the factors that affected the diagnostic sensitivity. METHODS: We retrospectively investigated 255 patients who underwent VBN-CBCT-guided transbronchial biopsy at our two centers from May 2021 to April 2022. A total of 228 patients with final diagnoses were studied. Patient characteristics including lesion size, lesion location, presence of bronchus sign, lesion type and imaging tool used were collected and analyzed. Diagnostic yield was reported overall and in groups using different imaging tools. RESULTS: The median size of lesion was 21 mm (range of 15.5-29 mm) with 46.1% less than 2 cm in diameter. Bronchus sign was present in 87.7% of the patients. The overall diagnostic yield was 82.1%, and sensitivity for malignancy was 66.3%. Patients with lesion > 2 cm or with bronchus sign were shown to have a significantly higher diagnostic yield. Four patients had bleeding and no pneumothorax occurred. CONCLUSION: Guided bronchoscopy with VBN and CBCT was an effective diagnostic method and was associated with a high diagnostic yield in a safe manner. In addition, the multivariant analysis suggested that lesion size and presence of bronchus sign could be a predictive factor for successful bronchoscopic diagnosis.

Bioinspired Dielectric Nanocomposites with High Charge-Discharge Efficiency Enabled by Superspreading-Induced Alignment of Nanosheets.

High-performance dielectric nanocomposites are promising candidates for thin-film dielectric capacitors for high-power pulse devices. However, the existing nanocomposites suffer from low charge-discharge efficiency (η), which results in severe generation and accumulation of Joule heat and subsequently the failure of the devices. In this work, we report nacre-inspired dielectric nanocomposites with outstanding η, which are enabled by superspreading shear flow-induced highly aligned two-dimensional (2D) nanofillers. Taking boron nitride nanosheets (BNNS) as an example, the highly aligned BNNS in the poly(vinylidene fluoride) (PVDF)-based nanocomposites contributes to a highly efficient Coulomb blockade effect for the injected charge carriers. Therefore, the bioinspired nanocomposites with highly aligned BNNS show significantly reduced dielectric loss (tan δ) (63.3%) and improved η (144.8%), compared to the ones with partially aligned nanosheets fabricated by solution casting. Furthermore, the optimized loading content of BNNS is as low as 3.6 wt %. The resulting nanocomposites exhibit reduced tan δ (0.018) and enhanced Eb (687 kV/mm), η (71%), and Ue (16.74 J/cm3). Our work demonstrates that the realization of high alignment of 2D nanofillers enabled by the superspreading shear flow is a promising way for the development of high-performance dielectric nanocomposites.

Chinese expert consensus on cone-beam CT-guided diagnosis, localization and treatment for pulmonary nodules.

Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Superspreading-Based Fabrication of Thermostable Nanoporous Polyimide Membranes for High Safety Separators of Lithium-Ion Batteries.

The development of thermally stable separators is a promising approach to address the safety issues of lithium-ion batteries (LIBs) owing to the serious shrinkage of commercial polyolefin separators at elevated temperatures. However, achieving controlled nanopores with a uniform size distribution in thermostable polymeric separators and high electrochemical performance is still a great challenge. In this study, nanoporous polyimide (PI) membranes with excellent thermal stability as high-safety separators is developed for LIBs using a superspreading strategy. The superspreading of polyamic acid solutions enables the generation of thin and uniform liquid layers, facilitating the formation of thin PI membranes with controllable and uniform nanopores with narrow size distribution ranging from 121 ± 5 nm to 86 ± 6 nm. Such nanoporous PI membranes display excellent structural stability at elevated temperatures up to 300 °C for at least 1 h. LIBs assembled with nanoporous PI membranes as separators show high specific capacity and Coulombic efficiency and can work normally after transient treatment at a high temperature (150 °C for 20 min) and high ambient temperature, indicating their promising application as high-safety separators for rechargeable batteries.

Bronchoscopic instillation of amphotericin B is a safe and effective measure to treat pulmonary mycosis.

Background and objectives: In recent years, there has been a significant increase in the prevalence of pulmonary mycosis disease, and its mortality has increased. There are very few studies on treating pulmonary mycosiss with bronchoscopic instillation of amphotericin B. This study investigated the clinical efficacy and safety of bronchoscopic instillation of amphotericin B for treating pulmonary mycosiss. Methods: This was a multi-centre, retrospective clinical study of 80 patients with pulmonary mycosiss who were treated with bronchoscopic instillation of amphotericin B. The efficacy and safety of this treatment were evaluated. Results: Eighty patients were included {51 males; mean [standard deviation (SD)] age, 46 (15.9) years}. The most common underlying cause was haematological malignancy (73.75%). The mean number of bronchoscopic instillations of amphotericin B was 2.4 (SD 1.5). In terms of treatment success, 58 (72.5%) patients achieved complete or partial changes on imaging after treatment. A total of 62 (77.5%) patients achieved complete or partial changes on imaging and/or local limitation of the mycosis infection. Seventy-six (95%) patients achieved complete or partial changes on imaging and/or local limitation of mycosis infection and/or an immunotherapy time window. The efficacy rates for treatment of Aspergillus and Mucor infections in terms of the three treatment success criteria described above were 73.81% vs. 63.64%, 80.95% vs. 72.73%, and 92.86% vs. 90.91%, respectively. Conclusion: Bronchoscopic instillation of amphotericin B is safe and effective for treatment of pulmonary mycosiss.

DOX-loaded mesoporous hydroxyapatite modified by hyaluronic acid can achieve efficient targeted therapy for lung cancer.

It is a novel therapeutic strategy to suppress tumour growth and metastasis by regulating the interaction between bioactivity ions and the biological process of tumour cells. This study synthesised a mesoporous hydroxyapatite (MHAP)-based nanocarrier for targeted delivery of the anti-cancer drug doxorubicin (DOX). To further strengthen the targeting of DOX-loaded nanocarrier to tumour, HA that could specifically identify receptor on the surface of tumours was functionally modified. The drug release properties curve showed that the MHAP-HA@DOX complex showed pH-sensitive and sustained release properties. Also, the MHAP-HA@DOX complex represented high toxicity against lung cancer A549 cells. Besides, it displayed a significant inhibitory effect on tumour growth rate in tumour-bearing mice, while no evident toxicity for mice was observed. This nano-material is hoped to be an effective and novel nano-drug for lung cancer.

CO2-elevated cell-free protein synthesis.

Gases are the vital nutrition of all organisms as the precursor of metabolism pathways. As a potential biological process, protein synthesis is inevitably regulated by gas transport and utilization. However, the effect of carbon dioxide (CO2) present in many metabolic pathways on protein synthesis has not been studied well. In this work, carbon dioxide combined with oxygen was employed for cell-free protein synthesis (CFPS) in the tube-in-tube reactor with precise control of gas concentration. In this in vitro system, gases could directly affect the protein synthesis process without transmembrane transport. Varied concentrations of carbon dioxide (0-1%) and constant oxygen concentration (21%) were employed for CFPS to assess the effects. The cell-free reactions with 0.3% CO2 and 21% O2 showed the highest protein yields. The combined effect of CO2 and O2 also resulted in relatively high protein expression under high oxygen conditions (0.3% CO2 and 100% O2). Moreover, metabolomics assays were performed to gain insight into metabolic changes, which showed that CO2 slightly improved energy metabolism and redox balance. In particular, the extra supplied CO2 activated the decarboxylating reactions and removed toxic metabolites to recover the protein synthesis activity. The exploration of CO2 on protein synthesis could provide guiding implications for basic studies and biomanufacturing.

The combination of MnO2@Lipo-coated gefitinib and bevacizumab inhibits the development of non-small cell lung cancer.

It can be found from a large number of cancer treatments that use of anti-cancer drugs alone often presents low efficacy and high side effects. This study aims to develop a new drug carrier with tumor-specific response, controlled release in vivo and high tumor-suppressive property. Inorganic nano-materials MnO2 with pH and glutathione (GSH, abundant in cancer cells) responsiveness were used to construct sustained-release functional nano-liposome to be an excellent in vivo pH-sensitive drug delivery system. Some hydrophilic MnO2, gefitinib (Geb), and bevacizumab (Beb) were encapsulated in the phospholipid vesicles (liposomes), so as to integrate several anti-tumor drugs (MnO2-PDA@Lipo@Geb@Beb) to achieve effective treatment of non-small cell lung cancer (NSCLC). Part of the MnO2 nanorods on the lipid shell had the properties of pH and GSH responsiveness, which could further enhance anti-cancer efficacy. Cell assay results showed that MnO2-PDA@Lipo@Geb@Beb nano-drug had an effective inhibition on A549 cell progression and showed excellent biocompatibility. In vivo results further confirmed that MnO2-PDA@Lipo@Geb@Beb nano-drug could effectively inhibit the growth of NSCLC cells. Overall, it can be inferred from the above experimental results that the nanocomposite drug is expected to be widely used in the clinical application of lung cancer.

Application of Montgomery T-Tube Placement in Treating Cotton-Myer IV Subglottic Airway Atresia after Bi-Level Airway Recanalization.

OBJECTIVE: The purpose of this study is to explore the effectiveness and safety of Montgomery T-tube placement in treating Cotton-Myer IV subglottic airway atresia after bi-level airway recanalization. METHODS: This study is a retrospective study. 11 patients who were treated for IV subglottic airway atresia between January 2017 and January 2019 in the Second Affiliated Hospital of Jiaxing University were involved in this study. The 11 patients all had undergone tracheotomies at our hospital, and they were transferred to the Department of Pulmonary and Critical Care Medicine for Montgomery T-tube placement after bi-level airway recanalization when their subglottic airway was atretic. Patients were observed for their clinical manifestations after placement. The effectiveness of T-tube placement after bi-level airway recanalization was assessed. The incidence of short-term and long-term complications after surgery was assessed. Patients were followed up for 3 to 24 months for evaluating their airway recovery. RESULTS: T-tubes were successfully placed in 11 patients. The atretic airways of all patients were recanalized after treatment. Eight patients got restoration of vocal ability, and 3 patients could only say simple words. None of the patients needed assisted oxygen inhalation. The SpO2 average level was increased from 95 ± 2% before treatment to 97 ± 3% after treatment. Patients had significant relief of cough or sputum, and they had less difficulty in dyspnea. All short- or long-term complications were self-relieved or controlled without further malignant progression after treatment by doctors. The average postoperative extubating time was (14.86 ± 3.62) months. CONCLUSION: The application of Montgomery T-tube placement in treating Cotton-Myer IV subglottic airway atresia after bi-level airway recanalization is well effective and safe for patients, and it can be promoted in clinical treatment.

An integrated epigenomic-transcriptomic landscape of lung cancer reveals novel methylation driver genes of diagnostic and therapeutic relevance.

Background: Aberrant DNA methylation occurs commonly during carcinogenesis and is of clinical value in human cancers. However, knowledge of the impact of DNA methylation changes on lung carcinogenesis and progression remains limited. Methods: Genome-wide DNA methylation profiles were surveyed in 18 pairs of tumors and adjacent normal tissues from non-small cell lung cancer (NSCLC) patients using Reduced Representation Bisulfite Sequencing (RRBS). An integrated epigenomic-transcriptomic landscape of lung cancer was depicted using the multi-omics data integration method. Results: We discovered a large number of hypermethylation events pre-marked by poised promoter in embryonic stem cells, being a hallmark of lung cancer. These hypermethylation events showed a high conservation across cancer types. Eight novel driver genes with aberrant methylation (e.g., PCDH17 and IRX1) were identified by integrated analysis of DNA methylome and transcriptome data. Methylation level of the eight genes measured by pyrosequencing can distinguish NSCLC patients from lung tissues with high sensitivity and specificity in an independent cohort. Their tumor-suppressive roles were further experimentally validated in lung cancer cells, which depend on promoter hypermethylation. Similarly, 13 methylation-driven ncRNAs (including 8 lncRNAs and 5 miRNAs) were identified, some of which were co-regulated with their host genes by the same promoter hypermethylation. Finally, by analyzing the transcription factor (TF) binding motifs, we uncovered sets of TFs driving the expression of epigenetically regulated genes and highlighted the epigenetic regulation of gene expression of TCF21 through DNA methylation of EGR1 binding motifs. Conclusions: We discovered several novel methylation driver genes of diagnostic and therapeutic relevance in lung cancer. Our findings revealed that DNA methylation in TF binding motifs regulates target gene expression by affecting the binding ability of TFs. Our study also provides a valuable epigenetic resource for identifying DNA methylation-based diagnostic biomarkers, developing cancer drugs for epigenetic therapy and studying cancer pathogenesis.

Innovative method for Amplatzer device implantation in patients with bronchopleural fistulas.

BACKGROUND: Bronchopleural fistula (BPF) is a relatively rare complication after various types of pulmonary resection. The double-sided mushroom-shaped occluder (Amplatzer device, AD) has been gradually used for BPF blocking due to its reliable blocking effect. We have improved the existing AD implantation methods to facilitate clinical use and named the new approach Sheath-free method (SFM). The aim of the present report was to explore the reliability and advantages of the SFM in AD implantation. METHODS: We improved the existing implantation methods by abandoning the sheath of the AD and using the working channel of the bronchoscope to directly store or release the AD without general anesthesia, rigid bronchoscopy, fluoroscopy, or bronchography. A total of 6 patients (5 men and 1 woman, aged 66.67 ± 6.19 years [mean ± SD]) had BPF blocking and underwent the SFM in AD implantation. RESULTS: AD implantation was successfully performed in all 6 patients with the SFM, 4 persons had a successful closure of the fistula, one person died after few days and one person did not have a successful closure of the fistula. The average duration of operation was 16.17 min (16.17 ± 4.67 min [mean ± SD]). No patients died due to operation complications or BPF recurrence. The average follow-up time was 13.2 months (range 10-17 months). CONCLUSION: We observed that the SFM for AD implantation-with accurate device positioning and a clear field of vision-is efficient and convenient. The AD is effective in BPF blocking, and could contribute to significantly improved symptoms of patients.

Rapid degradation of refractory organic pollutants by continuous ozonation in a micro-packed bed reactor.

Recently microreactor technology attracts attention due to the excellent multiphase mixing and enhanced mass transfer. Herein, a continuous ozonation system based on a micro-packed bed reactor (µPBR) was used to improve the dissolution rate of ozone and achieved a rapid and efficient degradation of refractory organic pollutants. The effects of liquid flow rate, gas flow rate, initial pH, initial O3 concentration and initial phenol concentration on the phenol and chemical oxygen demand (COD) removal efficiencies were also investigated. Experimental results showed that phenol and COD removal efficiencies under optimal conditions achieved 100.0% and 86.4%, respectively. Compared with large-scale reactors, the apparent reaction rate constant in µPBR increased by 1-2 orders of magnitude. In addition, some typical organic pollutants (including phenols, antibiotics and dyes) were treated by ozonation in µPBR. The removal efficiencies of these organic pollutants and COD achieved 100.0% and 70.2%-80.5% within 71 s, respectively. In this continuous treatment system, 100% of the unreacted ozone was converted to oxygen, which promoted the healthy development of aquatic ecosystems. Thus, this continuous system based on µPBR is a promising method in rapid and efficient treating refractory organic pollutants.

Gefitinib encapsulation based on nano-liposomes for enhancing the curative effect of lung cancer.

Gefitinib (GEB) is one of the drugs used for patients with epidermal growth factor receptor (EGFR)-positive mutations in non-small cell lung cancer (NSCLC). However, application of GEB is limited by its low water solubility, stability, and utilization rate, especially the side effects while GEB is given by oral. In this study, nanoliposome was used as a carrier to prepare nanoliposome compound drug (GL) by embedding GEB in the nanoliposome perfectly combined with green nontoxic solvent and thin-film dispersion method. The nanoliposome structure was expected to improve the water solubility and biocompatibility of GEB, thus improving the effect of cancer treatment. The surface electronegative nanoliposomes can effectively avoid protein adsorption and prolong the circulation time in vivo. Meanwhile, the ratio of lecithin to cholesterol (LE/CH) was explored to maximize the encapsulation efficiency of nanoliposome. Subsequent test results showed that GL exhibited better stability, smaller particle size and higher encapsulation efficiency. In addition, in vitro drug release curve also further confirmed that GL had a promising drug sustained-release effect. In particular, a series of in vitro tests such as cell activity, apoptosis, colony formation, scratch, invasion, and cell cycle assays were performed. The results indicated that GL significantly enhanced the pro-apoptotic effect on A549 cells. Most cell cycles of A549 cells were blocked in the G0/G1 phase influenced by GL, thus inhibiting the proliferation of cancer cells. In vivo anti-tumor studies showed that compared with pure GEB, GL had a significant inhibiting effect on NSCLC. In conclusion, the GL which was synthesized by a simple method in this study significantly improved the treatment effect of cancer cells, which proved that the nanoliposome carrier had an excellent application prospect in the treatment of lung cancer.

Application Value of Vital Signs Telemetry System for 2019 Novel Coronavirus Disease Suspected Cases in Isolation Wards.

OBJECTIVE: A large number of isolation wards were built to screen suspected patients because of the outbreak of coronavirus disease 2019 (COVID-19). The particularity of the isolation wards would lead to more medical resource consumption and heavier hospital control tasks. Therefore, we adopted a vital signs telemetry system in the isolation wards to improve this situation. MATERIALS AND TECHNOLOGIES: Twenty sets of vital signs telemetry system were installed in the east district of the isolation area and the wards were used as the telemetry system wards (TSWs). The wards in the west district were used as the routine wards (RW). The daily telephone questionnaire was used to collect the frequency and time of ward rounds by medical staff and lasted for one week. RESULTS: Within one-week survey, the average frequency of RW rounds was 3.00 ± 1.00 times per day, and the average time was 93.57 ± 66.25 min. The daily frequency of RW rounds was 0.428 ± 0.394 times per capita, and the time was 7.88 ± 2.36 min. There was a statistically significant difference in the time of ward rounds per capita, which presented that the daily time of TSW rounds per capita was shorter than that of RW rounds. No security events related to telemetry equipment were found throughout the study. CONCLUSION: The application of vital signs telemetry system as an alternative to traditional ward monitoring is considered feasible. The use of telemetry system can significantly reduce the consumption of medical resources, the workload of medical staff along with the administration and labor cost for isolation wards. The telemetry system provides sensitive and reliable real-time monitoring for the key indicators used for disease judgment and can make an accurate warning of the patients with disease aggravation in time. Thus, it is worthy of promotion and wide application.

tRNA-derived RNA fragments in cancer: current status and future perspectives.

Non-coding RNAs (ncRNAs) have been the focus of many studies over the last few decades, and their fundamental roles in human diseases have been well established. Transfer RNAs (tRNAs) are housekeeping ncRNAs that deliver amino acids to ribosomes during protein biosynthesis. tRNA fragments (tRFs) are a novel class of small ncRNAs produced through enzymatic cleavage of tRNAs and have been shown to play key regulatory roles similar to microRNAs. Development and application of high-throughput sequencing technologies has provided accumulating evidence of dysregulated tRFs in cancer. Aberrant expression of tRFs has been found to participate in cell proliferation, invasive metastasis, and progression in several human malignancies. These newly identified functional tRFs also have great potential as new biomarkers and therapeutic targets for cancer treatment. In this review, we focus on the major biological functions of tRFs including RNA silencing, translation regulation, and epigenetic regulation; summarize recent research on the roles of tRFs in different types of cancer; and discuss the potential of using tRFs as clinical biomarkers for cancer diagnosis and prognosis and as therapeutic targets for cancer treatment.

Exosome-Derived miR-486-5p Regulates Cell Cycle, Proliferation and Metastasis in Lung Adenocarcinoma via Targeting NEK2.

OBJECTIVE: This study aimed to describe the mechanism of exosome-derived miR-486-5p underlying the cell cycle and progression in lung adenocarcinoma (LUAD). METHODS: Bioinformatics methods were applied for identifying the differentially expressed genes (DEGs) in the GEO-LUAD dataset, predicting where the potential target miRNA was expressed and exploring the corresponding downstream target mRNA. qRT-PCR was conducted to detect the levels of the target genes in cancer cells. Thereafter, a series of in vitro experiments were performed for cell activities evaluation, including CCK-8, EdU, colony formation assay and transwell. Besides, Western blot was applied to determine the protein levels of the migration and invasion-related factors (NEK2, E-cadherin, N-cadherin, Vimentin, MMP-2, and MMP-9). Dual-luciferase reporter gene assay was employed for validating the targeted relationship between the target genes. Furthermore, nude mouse transplantation tumor experiment was conducted to further validate the role of the target miRNA in tumor development, and immunohistochemistry was used for Ki67 detection and TUNEL was applied for cell apoptosis assay. RESULTS: miR-486-5p was observed to be enriched in serum exosomes, and seen to be significantly down-regulated in cancer tissues as well as in cancer serum exosomes. It was proven that exosomes could release miR-486-5p, thus regulating LUAD progression and affecting cell cycle. Moreover, NEK2 was identified as a target of miR-486-5p both in vivo and in vitro. Enrichment analysis revealed that NEK2 was mainly activated in cell cycle and mitosis-related pathways. Meanwhile, NEK2 was found to present significant difference in different TNM stages. Furthermore, rescue experiments indicated that the inhibitory effect of miR-486-5p overexpression on LUAD progression could be abrogated when miR-486-5p and NEK2 were simultaneously up-regulated. CONCLUSION: Exosome-derived miR-486-5p is responsible for cell cycle arrest as well as the inhibition of cell proliferation and metastasis in LUAD via targeting NEK2.

O2-Tuned Protein Synthesis Machinery in Escherichia coli-Based Cell-Free System.

Involved in most aerobic biochemical processes, oxygen affects cellular functions, and organism behaviors. Protein synthesis, as the underlying biological process, is unavoidably affected by the regulation of oxygen delivery and utilization. Bypassing the cell wall, cell-free protein synthesis (CFPS) systems are well adopted for the precise oxygen regulation analysis of bioprocesses. Here a reliable flow platform was developed for measuring and analyzing the oxygen regulation on the protein synthesis processes by combining Escherichia coli-based CFPS systems and a tube-in-tube reactor. This platform allows protein synthesis reactions conducted in precisely controlled oxygen concentrations. For analysis of the intrinsic role of oxygen in protein synthesis, O2-tuned CFPS systems were explored with transcription-translation related parameters (transcripts, energy, reactive oxygen species, and proteomic pathway analysis). It was found that 2% of oxygen was the minimum requirement for protein synthesis. There was translation-related protein degradation in the high oxygen condition leading to a reduction. By combining the precise gas level controlling and open biosystems, this platform is also potential for fundamental understanding and clinical applications by diverse gas regulation in biological processes.

The Functional Effects of Key Driver KRAS Mutations on Gene Expression in Lung Cancer.

Lung cancer is a common malignant cancer. Kirsten rat sarcoma oncogene (KRAS) mutations have been considered as a key driver for lung cancers. KRAS p.G12C mutations were most predominant in NSCLC which was comprised about 11-16% of lung adenocarcinomas (p.G12C accounts for 45-50% of mutant KRAS). But it is still not clear how the KRAS mutation triggers lung cancers. To study the molecular mechanisms of KRAS mutation in lung cancer. We analyzed the gene expression profiles of 156 KRAS mutation samples and other negative samples with two stage feature selection approach: (1) minimal Redundancy Maximal Relevance (mRMR) and (2) Incremental Feature Selection (IFS). At last, 41 predictive genes for KRAS mutation were identified and a KRAS mutation predictor was constructed. Its leave one out cross validation MCC was 0.879. Our results were helpful for understanding the roles of KRAS mutation in lung cancer.

Exploring the Effect of Differentially Expressed Long Non-coding RNAs Driven by Copy Number Variation on Competing Endogenous RNA Network by Mining Lung Adenocarcinoma Data.

Lung cancer is the first cause of cancer death, and gene copy number variation (CNV) is a vital cause of lung cancer progression. Prognosis prediction of patients followed by medication guidance by detecting CNV of lung cancer is emerging as a promising precise treatment in the future. In this paper, the differences in CNV and gene expression between cancer tissue and normal tissue of lung adenocarcinoma (LUAD) from The Cancer Genome Atlas Lung Adenocarcinoma data set were firstly analyzed, and greater differences were observed. Furthermore, CNV-driven differentially expressed long non-coding RNAs (lncRNAs) were screened out, and then, a competing endogenous RNA (ceRNA) regulatory network related to the gene CNV was established, which involved 9 lncRNAs, seven microRNAs, and 178 downstream messenger RNAs (mRNAs). Pathway enrichment analyses sequentially performed revealed that the downstream mRNAs were mainly enriched in biological pathways related to cell division, DNA repair, and so on, indicating that these mRNAs mainly affected the replication and growth of tumor cells. Besides, the relationship between lncRNAs and drug effects was explored based on previous studies, and it was found that LINC00511 and LINC00942 in the CNV-associated ceRNA network could be used to determine tumor response to drug treatment. As examined, the drugs affected by these two lncRNAs mainly targeted metabolism, target of rapamycin signaling pathway, phosphatidylinositol-3-kinase signaling pathway, epidermal growth factor receptor signaling pathway, and cell cycle. In summary, the present research was devoted to analyzing CNV, lncRNA, mRNA, and microRNA of lung cancer, and nine lncRNAs that could affect the CNV-associated ceRNA network we constructed were identified, two of which are promising in determining tumor response to drug treatment.

Long noncoding RNA LCAT1 functions as a ceRNA to regulate RAC1 function by sponging miR-4715-5p in lung cancer.

INTRODUCTION: Long noncoding RNAs (lncRNAs) are emerging as key players in the development and progression of cancer. However, the biological role and clinical significance of most lncRNAs in lung carcinogenesis remain unclear. In this study, we identified and explored the role of a novel lncRNA, lung cancer associated transcript 1 (LCAT1), in lung cancer. METHODS: We predicted and validated LCAT1 from RNA-sequencing (RNA-seq) data of lung cancer tissues. The LCAT1-miR-4715-5p-RAC1 axis was assessed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Signaling pathways altered by LCAT1 knockdown were identified using RNA-seq. Furthermore, the mechanism of LCAT1 was investigated using loss-of-function and gain-of-function assays in vivo and in vitro. RESULTS: LCAT1 is an oncogene that is significantly upregulated in lung cancer tissues and associated with poor prognosis. LCAT1 knockdown caused growth arrest and cell invasion in lung cancer cells in vitro, and inhibited tumorigenesis and metastasis in the mouse xenografts. Mechanistically, LCAT1 functions as a competing endogenous RNA for miR-4715-5p, thereby leading to the upregulation of the activity of its endogenous target, Rac family small GTPase 1 (RAC1). Moreover, EHop-016, a small molecule inhibitor of RAC1, as an adjuvant could improve the Taxol monotherapy against lung cancer cells in vitro. CONCLUSIONS: LCAT1-miR-4715-5p-RAC1/PAK1 axis plays an important role in the progression of lung cancer. Our findings may provide valuable drug targets for treating lung cancer. The novel combination therapy of Taxol and EHop-016 for lung cancer warrants further investigation, especially in lung cancer patients with high LCAT1 expression.