Objective: Specific methylation sites have shown promise in the early diagnosis of lung adenocarcinoma (LUAD). However, their utility in predicting LUAD prognosis remains unclear. This study aimed to construct a reliable methylation-based predictor for accurately predicting the prognosis of LUAD patients.Method: DNA methylation data and survival data from LUAD patients were obtained from the TCGA and a GEO series. A DNA methylation-based signature was developed using univariate least absolute shrinkage and selection operators and multivariate Cox regression models.Result: Eight CpG sites were identified and validated as optimal prognostic signatures for the overall survival of LUAD patients. Receiver operating characteristic analysis demonstrated the high predictive ability of the eight-site methylation signature combined with clinical factors for overall survival.Conclusion: This research successfully identified a novel eight-site methylation signature for predicting the overall survival of LUAD patients through bioinformatic integrated analysis of gene methylation markers used in the early diagnosis of lung cancer.

Several targeted immunotherapies have recently showed significant advances in treatment of non-small cell lung cancer (NSCLC), including antibodies and inhibitors targeting programmed death-1 (PD-1) and its ligand (PD-L1). Tumor tissue samples were prospectively collected from 183 patients with NSCLC including lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). PD-L1 expression level was measured by immunohistochemistry assay and tumor mutational burden (TMB) status was assessed by next generation sequencing. Correlations between PD-L1 expressions, TMB status with clinicopathological characteristics were analyzed. PD-L1 expression was detected in 37% of ADC group and 55% in SQCC group while all clinicopathological characteristics were found comparable between these two groups. PD-L1 expression was negatively associated with overall survival in ADC group (P < 0.0001) but not in SQCC group (P = 0.418). In consistent with PD-L1 expression level, TMB status was significantly lower in ADC subjects as compared to SQCC subjects (P = 0.024) while PD-L1 positive subgroup and TMB high subgroup shared less subjects within ADC group than SQCC group. More importantly, the combination of TMB status and PD-L1 expression successfully identified responders, who showed significant longer median overall survival than non-responders (32 months vs. 8.5 months) in ADC subjects (P < 0.0001) but not in SQCC subjects. Here we tested the hypothesis that monitoring TMB, in addition to the existing PD-L1 expression level, could represent valuable non-invasive biomarkers for the chemotherapy and targeted therapy. Further analyses are in need to further assess the prognostic value of TMB for ADC and SQCC patients receiving immunotherapy.

Background: Although lobectomy is still the preferred treatment for patients with stage I non-small cell lung cancer (NSCLC), segmentectomy or wedge resection is frequently performed on patients who cannot withstand the physiological rigors of lobectomy. The objective of this study was to compare the overall survival (OS), cancer-specific survival (CSS), and disease-free survival outcomes among patients with stage I NSCLC who have undergone these procedures. Methods: A systematic electronic search in three online databases was conducted from their earliest publication dates to June 2015. The studies were evaluated according to rigorous, predefined inclusion criteria. The hazard ratio (HR) was used as the outcome measure for data combining. Results: There were nine eligible studies. These studies included 1181 patients who underwent segmentectomy and 2003 patients who underwent wedge resection. Stage I NSCLC patients who underwent segmentectomy had significantly better OS (HR 0.80; 95% confidence interval [CI], 0.68–0.93; p = 0.004) and CSS (HR 0.42; 95% CI, 0.20–0.88; p = 0.02) rates than those who underwent wedge resection. However, there were no significant differences in OS (HR 0.39; 95% CI, 0.15–1.02; p = 0.06) and CSS (HR 1.87; 95% CI, 0.29–12.06; p = 0.51) rates between segmentectomy and wedge resection in patients with stage Ia NSCLC with tumor size ⩽ 2 cm. Conclusions: For patients with stage I NSCLC, segmentectomy results in higher survival rates than wedge resection, whereas the outcomes of wedge resection are comparable to those of segmentectomy for patients with stage Ia NSCLC with tumor size ⩽ 2 cm. Considering the limitations and heterogeneity of the included studies, this conclusion should be further confirmed by rigorous randomized clinical trials.

Background: PD‐1/PD‐L1 tumor immunotherapy shows effective anticancer in treatment of solid tumors, so PEI lipid nanoparticles (PEI‐LNP)/siRNA complex (EPV‐PEI‐LNP‐SiRNA) with the therapeutic function of PD‐L1‐siRNA and EGFR short peptide/PD‐L1 double immune‐enhancing function were constructed for the prevention and treatment of EGFR‐positive lung cancer in this study.Method: In this study, PEI lipid nanoparticles (PEI‐LNP)/siRNA complex (EPV‐PEI‐LNP‐siRNA) with the therapeutic function of PD‐L1‐siRNA and EGFR short peptide/PD‐L1 double immune‐enhancing function were constructed for the prevention and treatment of EGFR‐positive lung cancer and functional evaluation was conducted.Results: On the basis of the construction of the composite nano‐drug delivery system, the binding capacity, cytotoxicity, apoptosis and uptake capacity of siRNA and EPV‐PEI‐LNP were tested in vitro, and the downregulation effect of PD‐L1 on A549 cancer cells and the cytokine levels of cocultured T cells were tested. Lipid nanoparticles delivered siRNA and EGFR short peptide vaccine to non‐small cell lung cancer (NSCLC), increasing tumor invasion and activation of CD8 + T cells. Combination therapy is superior to single target therapy.Conclusion: Our constructed lipid nanoparticles of tumor targeted therapy gene siRNA combination had the ability to target cells in vitro and downregulate the expression of PD‐L1, realizing the tumor‐specific expression of immune‐stimulating cytokines, which is a highly efficient and safe targeted therapy nano‐vaccine.

The purpose of this study is to detect the Parkinson’s disease gene family mRNA relative expression in the non-small-cell lung cancer (NSCLC) tumor tissue and analyze the association between tumor characteristics and the Parkinson’s disease gene family. Tumor tissue and tumor-adjacent tissue of 114 NSCLC patients were collected and SYBR quantitative analysis was used to detect the relative expression level of nine Parkinson’s disease gene mRNAs. Then, paired sample test, two-sided Student’s t-test, or two-sided Wilcoxon rank sum test was performed to analyze the mRNA relative expression level of nine Parkinson’s disease gene mRNAs in different gender, tumor histology, and tumor stage. Overexpression in the tumors was detected in 46/114 (40.35 %) PARK1/4, 74/114 (64.91 %) PARK2, 104/114 (91.23 %) PARK5, 95/114 (83.33 %) PARK6, 80/114 (70.18 %) PARK7, 55/114 (48.25 %) PARK8, 100/114 (87.72 %) PARK9, 55/114 (48.25 %) PARK15, and 99/114 (86.84 %) glucocerebrosidase (GBA). Five genes PARK5 (91.23 %), PARK6 (83.33 %), PARK7 (70.18 %), PARK9 (87.72 %), and GBA (86.84 %) were supposed to be overexpressed in the lung tumor tissues compared with tumor-adjacent tissues. There was no significant difference in PARK1/4, PARK2, PARK5, PARK9, and GBA mRNA expression by different tumor stage, whereas, PARK6, PARK7, PARK8, and PARK15 mRNA expression were found to have significant difference in the comparison of different tumor stages. The expression of PARK6 (P = 0.01, P = 0.03) and PARK15 (P < 0.001, P < 0.001) were significantly higher in stages I and II when compared with stage III, respectively. NSCLC patients in stage I showed the higher expression PARK7 compared to the patients in stage II (P = 0.003). The high expression of PARK6, PARK7, and PARK15 might lead to the occurrence of a primary NSCLC tumor, and the tumor with a decreasing expression of these three genes tends to be stages II and III. The results of our study indicate that the Parkinson’s disease gene family may be a potential marker for the prediction of NSCLC.

In recent years, more and more studies have shown that antiparasitic drugs can affect a variety of biological processes of tumor cells and exhibit a potential anti-tumor activity. Although artesunate (ART), a strong bioactive derivative of artemisinin and widely used clinically against malaria, was found to have an inhibitory effect on tumor cells, it is still unclear whether ART could regulate the tumor malignancy of non-small-cell lung cancer (NSCLC) cells. In this study, we aimed to investigate the effect of ART on migration capacities in NSCLC cell lines of A549 and H1975. Cell migration capacity was remarkably inhibited by ART treatment. The expression of epithelial marker E-cadherin was upregulated, while mesenchymal markers (N-cadherin, vimentin and FN1) were inhibited by ART in both protein and mRNA levels in A549 and H1975 cells, indicating ART could suppress the epidermal interstitial transformation (EMT) of NSCLC cells. Meanwhile, BTBD7 was found highly expressed in tumor tissues of NSCLC patient and associated with poor prognosis. The anti-migration activity of ART was found to be mediated by the inhibition of BTBD7 mRNA expression and was reversed when the cells were transiently transfected with the BTBD7 overexpression plasmid. Our study demonstrated the potent anti-migratory activity of ART, thereby presenting it as a new candidate for clinical therapy in NSCLC. Graphical abstract