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In the last decade, a relatively novel, ubiquitous and highly stable subclass of non-coding RNAs, called circular (circ)-RNAs, has increasingly been implicated in cancer development, and several of them have been shown to act as microRNA sponges. As yet, however, the role of circRNAs in lung adenocarcinoma (LUAD) development has largely remained unexplored.Bioinformatics, microarray-based and qRT-PCR expression assays were used to assess circRNA, miRNA and mRNA expression in LUAD patient samples and cell lines. siRNA-mediated silencing was used to assess the effect of circCSNK1G3 on various LUAD-associated characteristics such as proliferation, migration, invasion and tumorigenesis, both in vitro and in vivo. Western blotting, immunohistochemistry, fluorescence in situ hybridization (FISH) and luciferase reporter activity assays were used to characterize relationships between circCSNK1G3, miR-143-3p and HOXA10 in LUAD cells.By screening for differentially expressed circRNAs, we found that circCSNK1G3 was aberrantly expressed in primary LUAD tissues and cell lines. An oncogenic role of circCSNK1G3 was deduced from its aberrant expression and associated enhancement of LUAD A549 and H1299 cell proliferation, migration and invasion. We also found that circCSNK1G3 can directly interact with and suppress miR-143-3p expression by serving as a 'miR-143-3p sponge'. In addition, we found that circCSNK1G3 can modulate homeobox (HOX) A10 expression through miR-143-3p signaling and, thereby, affect LUAD tumorigenesis.Our data indicate that circCSNK1G3 can induce HOXA10 expression and, thereby, promote the growth and metastasis of LUAD cells through hsa-miR-143-3p sponging. As such, our data highlight the targetability of the circCSNK1G3/miR-143-3p/HOXA10 signaling axis in patients with LUAD. Graphical abstract.

Background Immune checkpoint inhibitors (ICIs) have witnessed the achievements of convincing clinical benefits that feature the significantly prolonged overall survival (OS) of patients suffering from advanced non-small cell lung cancer (NSCLC), according to reports recently. Sensitivity to immunotherapy is related to several biomarkers, such as PD-L1 expression, TMB level, MSI-H and MMR. However, a further investigation into the novel biomarkers of the prognosis on ICIs treatment is required. In addition, there is an urgent demand for the establishment of a systematic hazard model to assess the efficacy of ICIs therapy for advanced NSCLC patients. Methods In this study, the gene mutation and clinical data of NSCLC patients was obtained from the TCGA database, followed by the analysis of the detailed clinical information and mutational data relating to two advanced NSCLC cohorts receiving the ICIs treatment from the cBioPortal of Cancer Genomics. The Kaplan–Meier plot method was used to perform survival analyses, while selected variables were adopted to develop a systematic nomogram. The prognostic significance of ERBB4 in pan-cancer was analyzed by another cohort from the cBioPortal of Cancer Genomics. Results The mutation frequencies of TP53 and ERBB4 were 54% and 8% in NSCLC, respectively. The mutual exclusive analysis in cBioPortal has indicated that ERBB4 does show co-occurencing mutations with TP53. Patients with ERBB4 mutations were confirmed to have better prognosis for ICIs treatment, compared to those seeing ERBB4 wild type (PFS: exact p = 0.017; OS: exact p p = 0.021). The mutation status of ERBB4 and TP53 was tightly linked to DCB of ICIs treatment, PD-L1 expression, TMB value, and TIICs. Finally, a novel nomogram was built to evaluate the efficacy of ICIs therapy. Conclusion ERBB4 mutations could serve as a predictive biomarker for the prognosis of ICIs treatment. The systematic nomogram was proven to have the great potential for evaluating the efficacy of ICIs therapy for advanced NSCLC patients.

Activation of epidermal growth factor receptor signaling by kinase dimerization plays a crucial role in the development, progression, and metastasis of lung cancer. Tumor suppressor Mig-6 is a natural inhibitory protein of epidermal growth factor receptor signaling; the protein uses its two regions, namely segments 1 and 2, to directly interact with kinase dimerization interface and then inactivates the kinases. Here, we attempted to improve the binding capability of isolated segment 2 peptide to epidermal growth factor receptor family kinases by cyclizing the peptide. In the procedure, a disulfide bond was introduced across two ends of the peptide to constrain the peptide conformation in an antiparallel, double-stranded β-sheet. Molecular dynamics simulations indicated high-structural flexibility and intrinsic disorder associated with the linear peptide of Mig-6 segment 2, whereas its cyclized version exhibited a considerable rigidity and low mobility. Molecular mechanics/Poisson–Boltzmann surface area calculations and quasiharmonic analysis revealed that the cyclization influences kinase–peptide interaction enthalpy modestly, but can largely minimize entropy penalty upon the interaction, thus effectively restoring peptide binding free energy. Fluorescence polarization assays found no affinity of linear peptide to epidermal growth factor receptor family kinases, while a weak or moderate affinity can be observed for cyclic peptide binding to the kinases.

Background Aberrant DNA methylations are significantly associated with esophageal squamous cell carcinoma (ESCC). In this study, we aimed to investigate the DNA methylation-driven genes in ESCC by integrative bioinformatics analysis. Methods Data of DNA methylation and transcriptome profiling were downloaded from TCGA database. DNA methylation-driven genes were obtained by methylmix R package. David database and ConsensusPathDB were used to perform gene ontology (GO) analysis and pathway analysis, respectively. Survival R package was used to analyze overall survival analysis of methylation-driven genes. Results Totally 26 DNA methylation-driven genes were identified by the methylmix, which were enriched in molecular function of DNA binding and transcription factor activity. Then, ABCD1, SLC5A10, SPIN3, ZNF69, and ZNF608 were recognized as significant independent prognostic biomarkers from 26 methylation-driven genes. Additionally, a further integrative survival analysis, which combined methylation and gene expression data, was identified that ABCD1, CCDC8, FBXO17 were significantly associated with patients’ survival. Also, multiple aberrant methylation sites were found to be correlated with gene expression. Conclusion In summary, we studied the DNA methylation-driven genes in ESCC by bioinformatics analysis, offering better understand of molecular mechanisms of ESCC and providing potential biomarkers precision treatment and prognosis detection. Electronic supplementary material The online version of this article (10.1186/s12935-019-0770-9) contains supplementary material, which is available to authorized users.

Recent diagnostic procedure advances have greatly improved early lung cancer detection. However, the invasive, unpleasant and inconvenient nature of current diagnostic procedures limits their application. There is a great need of novel non-invasive biomarkers for early lung cancer diagnosis. In the present study, we intend to determine whether the blood signatures of p14ARF promoter methylation are suitable for early detection of lung cancer. The study aimed to assess the probability of p14ARF promoter methylation in plasma samples to detect early lung cancer using nested methylation-specific PCR in the training set consisted of tumor tissues and paired blood. Besides, we were further to discuss the difference in time to progression between methylation and unmethylation of p14ARF promoter using univariate and multivariate analysis. The methylation of p14ARF promoter was detected in 33.6 % of tumor tissues, and 12.1 and 25.2 % in distant-cancer mucosa and matched plasma, respectively, and our study has also demonstrated the positive correlation between them by Pearson’s test (r = 0.300). The tumor-free survival time of the unmethylation of p14ARF promoter is significantly longer than that of the methylation of p14ARF promoter in tumor tissues (χ 2 = 7.149, P = 0.008). The methylation of p14ARF promoter in plasma samples has strong potential as a novel non-invasive biomarker for early detection of lung cancer, and the methylation of p14ARF promoter was considered as prognostic factor in our study.

Background Despite the robotic surgery is widely applied, sleeve lobectomy for lung cancer using the Da Vinci surgical system is still less performed. We described a sleeve lobectomy for adenocarcinoma located at the left lower lobe using the Da Vinci surgical system. Case presentation A case of 57-year old female referred to our hospital. Computed tomography scan showed an occupation located at the left lower lobe and adenocarcinoma project from the lobe bronchus was diagnosed by bronchoscope examination. A sleeve lobectomy was performed using the Da Vinci surgical system and the postoperative recovery was uneventful. Conclusions Robotic thoracic surgery is feasible to perform sleeve lobectomy inspite of inadequate experience.

21 earthquakes recorded by a temporary seismic network in the Changbaishan Tianchi volcanic area in Northeast China operated during the summer of 2002 and 2003 were analyzed to estimate the S coda attenuation. The attenuation quality factor Qc was estimated using the single scattering attenuation model of Sato (1977) in the frequency band from 4 to 24 Hz. All the events studied in this paper occurred at depths from 2 to 6 km with ML of 1.4–2.8. The epicentral distances are less than 25 km. For all events which occurred near the Tianchi Lake (caldera), the Qc patterns obtained at the stations near the lake are similar, and the Qc values are relatively small. At the stations located about 15 km east of the Tianchi Lake, however, the average Qc is significantly higher. For an event which occurred 25km from the lake to the west, Qc patterns derived at the stations near the lake are quite similar to the above mentioned Qc for stations located in the east. Further study shows that Qc value in the north and central areas of the volcano is relatively lower than that in the surrounding area. Compared to other volcanic areas in the world, the average Qc of the Changbaishan Tianchi volcanic area is obviously lower. The deep seismic sounding and teleseismic receiver function studies indicated more than one lower velocity layer in the crust. The MT studies suggested the presence of high conductive bodies beneath the area. We interpret the strong attenuation of coda waves near the Changbaishan Tianchi volcano as being possibly related to high temperature medium caused by shallow magma chambers.

The mechanism of action of oncogenic or tumor suppressor microRNAs is not well understood. We examined the microRNA expression profile in completely resected lung adenocarcinoma and examined the associated response to erlotinib. The lung adenocarcinoma tissue and adjacent normal lung parenchyma of 226 stage IIB and IIIA patients who underwent complete resection were obtained for two separate retrospective cohorts. In cohort 1 (119 patients; 80 with epidermal growth factor receptor (EGFR) mutations and 39 without), miRNA microarrays were used to identify EGFR-related miRNAs and their association with survival. In cohort 2 (107 patients with EGFR mutations), the miRNAs and their association with survival and response to erlotinib were analyzed by qRT-PCR. Cox proportional hazards regression was used to evaluate the effect of treatment on survival. As a result, erlotinib is associated with a significant improvement in overall survival (P = 0.0075, cohort 1; P = 0.0372, cohort 2) and disease progression (P = 0.6929, cohort 1; P = 0.3347, cohort 2) in patients with reduced miRNA-21 expression. Additionally, miRNA-145 is strongly associated with overall survival (P = 0.0008, cohort 1; P = 0.0131, cohort 2) and progression-free survival (P = 0.0198, cohort 1; P = 0.0269, cohort 2). Understanding the response rate to erlotinib relative to miRNA-21 (77.3 vs. 41.7 %, P

Although the survival of lung cancer patients has improved significantly due to the development of early detective tools, lung cancer remains a leading cause of cancer-related death after curative surgery. So it is extremely important for cancer patients to predict early metastasis, especially pleural dissemination, the most frequent type of recurrence in patients after surgery. Based on a retrospective study of 86 curatively resected lung cancer patients (training set), we determined a cutoff value of NSE mRNA using receiver-operating characteristic curve. Then, we prospectively used this cutoff value to validate the risk of pleural recurrence in a new cohort of 81 lung cancer patients (validation set) between April 2009 and June 2010 by real-time reverse transcriptase-polymerase chain reaction. During the median 27 months of postoperative surveillance, 16 of the 81 patients died, and 9 of the 16 developed pleural metastases. Multivariate analysis with the Cox proportional hazards model showed that positive NSE mRNA was a significant independent risk factor with both overall survival and pleural recurrence-free survival (both P < 0.0001) as end points which were significantly worse in patients with positive NSE mRNA (P < 0.0001). These results indicate that quantitative NSE mRNA in pleural fluid is a reliable prognostic indicator of pleural recurrence in the clinical setting.