Background
The International Association for the Study of Lung Cancer (IASLC) proposed a novel grading system for invasive lung adenocarcinoma, but lymphatic invasion was not evaluated. Meanwhile, ...the scope of lymph node dissection in part-solid invasive lung adenocarcinoma (PSILA) is still controversial. Therefore, this study aims to explore preoperative risk factors for lymph node metastasis in PSILA, to provide reference for intraoperative dissection of lymph nodes.
Methods
From 2018 to 2020, clinical data of patients (stage cN0) consecutively diagnosed as PSILA were retrospectively analyzed and classified according to the novel grading system. Logistic regression was conducted to screen the clinicopathological factors of lymph node metastasis in PSILA.
Results
A large cohort of 960 patients with PSILA who underwent lobectomy or sub-lobectomy were enrolled. By logistic regression analyses, solid part size, bronchial cutoff sign, spiculation, and carbohydrate antigen 199 (CA199) were eventually identified as independent risk factors for lymph node metastasis, based on which a nomogram was built to preoperatively predict the risk of lymph node metastasis area under the receiver operating characteristic curve (AUC)=0.858; concordance index = 0.857; best cutoff, 0.027. This suggests that intraoperative systematic lymph node dissection is recommended when the predicted risk value exceeds 0.027. Reproducibility of the novel grading system was verified.
Conclusions
The novel IASLC grading system was applicative in real world. The nomogram for preoperative prediction of lymph node metastasis may provide reference for the lymph node dissection strategy during PSILA surgeries.
Firstly, observe the prognostic significance and the biological functional effects of gap junction protein beta 2 (
or Cx26) in lung adenocarcinoma (LUAD). Subsequently, explore the role played by
in ...intercellular communication by single-cell RNA sequencing.
We made a differential analysis of
expression through public databases and investigated the clinical characteristics and prognostic significance. ESTIMATE analysis and Tumor Immune Estimation Resource (TIMER) database were utilized to illustrate the association of
with immune infiltration and components of the tumor microenvironment. Gene Ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Gene set enrichment analysis (GSEA) were performed to study the biological function of
. Cell-cell communication was analyzed using the CellChat R package through sc-RNA data.
has an outstanding prognosis value in LUAD and a close relationship was found between
and immune infiltration in LUAD.
could participate in several tumor biological processes, including extracellular matrix remodeling and upregulation of multiple cancer-related active pathways.
related hub-genes influence intercellular communication through the SPP1 signaling pathway.
Our study illustrates one mechanism by which
exerts its cancer-specific relevant effects, that is, causing changes in intercellular communication through the SPP1 signaling pathway. Blockade of this pathway may limit the functional role of
and provide us with promising new perceptions for LUAD treatment.
Introduction:
Lung adenocarcinoma is a common cause of mortality in patients with cancer. Recent studies have indicated that copper-related cell death may not occur in the same way as previously ...described. Long non-coding RNAs (lncRNAs) play a key role in the occurrence and development of tumors; however, the relationship between cuproptosis and lncRNAs in tumorigenesis and lung adenocarcinoma (LUAD) treatment has not been well established. Our study aimed to construct a model to analyze the prognosis of lung adenocarcinoma in patients using a carcinogenesis-related lncRNA (CR) signature.
Methods:
The transcriptional profiles of 507 samples from The Cancer Genome Atlas were assessed. Cox regression and co-expression analyses, and the least absolute shrinkage and selection operator (LASSO) were used to filter the CR and develop the model. The expression status of the six prognostic CRs was used to classify all samples into high- and low-risk groups. The overall disease-free survival rate was compared between the two groups. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used to identify the pathways and mechanisms involved in this model. Subsequently, immunotherapy response, sensitivity, and correlation analyses for several anti-tumor medications were performed.
In vitro
experiments, including qPCR, were conducted in nine lung adenocarcinoma cell lines and 16 pairs of lung adenocarcinoma and para-carcinoma tissues.
Results:
After confirmation using the ROC curve, patients in the low-risk category benefited from both overall and disease-free survival. Gene Ontology analysis highlighted cell movement in the model. In the
in vitro
experiments, qPCR results showed the expression levels of six CRs in 16 pairs of carcinoma and para-carcinoma tissues, which were in accordance with the results of the model. AL138778.1 is a protective factor that can weaken the invasion and migration of A549 cells, and AL360270.1 is a hazardous factor that promotes the invasion and migration of A549 cells. According to this model, targeted treatments such as axitinib, gefitinib, linsitinib, pazopanib, and sorafenib may be more appropriate for low-risk patients.
Conclusion:
Six CR profiles (AL360270.1, AL138778.1, CDKN2A-DT, AP003778.1, LINC02718, and AC034102.8) with predictive values may be used to evaluate the prognosis of patients with lung adenocarcinoma undergoing therapy.
Purpose: Immune checkpoint inhibitors (ICIs) have been successfully used in many clinical trials related to immunotherapy. This study aimed to investigate the clinical efficacy of ICIs and prognostic ...factors in patients with resectable non-small cell lung cancer (NSCLC) following neoadjuvant therapy in the real world.Methods: A total of 170 consecutive patients were finally selected and divided into two groups: the preoperative chemotherapy group (n = 91) and the chemo-immunotherapy group (n = 79). The primary endpoint was disease-free survival (DFS). The secondary endpoints were pathological response, clinical response, pathological nodal disease, and ability of multivariate Cox regression analysis to predict survival. Survival was estimated using Kaplan–Meier method and compared using log-rank test.Results: There was a statistically significant difference in DFS between the two groups (log-rank test, P = 0.019). Multivariate Cox regression analysis showed that maximum tumor diameter (P = 0.016), higher lymph node stage (ypN1, P = 0.016; ypN2, P <0.001), and major pathological response not achieved (non-major pathological response MPR, P = 0.011) were independent prognostic factors for worse DFS.Conclusion: Neoadjuvant chemo-immunotherapy yields better effects in pathological and clinical response than chemotherapy alone, which is also associated with longer DFS in the treatment of locally advanced NSCLC. Moreover, a larger tumor specimen diameter, higher ypN staging, and non-MPR after neoadjuvant therapy were associated with worse prognosis.
A proof-of-concept for the fabrication of novel anti-biofouling water purification membranes through the incorporation of a 2-aminoimidazole (2-AI) during membrane casting is presented. 2-AI ...molecules are known to inhibit biofouling through the disruption of biofilm formation mechanisms, not through the inactivation of bacteria. Three approaches to incorporation were evaluated, adding the 2-AI to either one of the two monomer solutions, (a) m-phenylene diamine or (b) trimesoyl chloride, that polymerize to make a polyamide active layer, or by (c) reacting the active layer with a post-polymerization-2-AI-soak solution. These methods of incorporation are directly translatable to current membrane fabrication practices without the addition of other chemicals aside from the 2-AIs themselves. Results showed that the 2-AI was incorporated into the active layer of the membranes at concentrations (0.16–0.93 M) orders of magnitude higher than what is required for biofilm inhibition (IC50 = 162–420 μM). The 2-AI membranes significantly (p = 0.002–0.04) inhibited Pseudomonas aeruginosa biofilms (49–90% on average) due to the presence and action of 2-AI, not physico-chemical changes. The 2-AI-soak approach produced membranes that had the most stable incorporation, with no loss of compound during use and cleaning, and the highest biofilm inhibition, at 90% inhibition on average. The incorporation of 2-AI into the membranes decreased water permeability by 26–44% and salt rejection by 1.2–4.3% points, as compared to control membranes. No attempt was made to optimize 2-AI membrane preparation toward minimization of changes in water permeability and salt rejection. Given the substantial biofilm formation inhibition exhibited by the 2-AI membranes, and the limited decrease observed in water permeability and salt rejection, the 2-AI membranes presented in this study support 2-AI incorporation into polyamide active layers as a promising avenue to enhance current water purification membranes.
•Biofilm was significantly inhibited (39–92%) by 2-aminoimidazole (2-AI) membranes.•2-AI incorporated (0.16–0.95 M) during casting for scalable antibiofouling membranes.•Post-polymerization 2-AI-soak produced the most stable and effective 2-AI membrane.•Biofilm inhibition attributed to 2-AI, not changes in physico-chemical properties.
Given that abnormal autophagy is involved in the pathogenesis of cancers, we sought to explore the potential value of autophagy-associated genes in lung adenocarcinoma (LUAD).
RNA sequencing and ...clinical data on tumour and normal samples were acquired from The Cancer Genome Atlas (TCGA) database and randomly assigned to training and testing groups. Differentially expressed autophagy-associated genes (AAGs) were screened. Within the training group, Cox regression and Lasso regression analyses were conducted to screen five prognostic AAGs, which were used to develop a model. Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were plotted to determine the performance of the model in both groups. Immunohistochemistry was used to demonstrate the differential expression of AAGs in tumour and normal tissues at the protein level. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were utilized to further elucidate the roles of AAGs in LUAD.
The data from the TCGA database included 497 tumour and 54 normal samples, within which 30 differentially expressed AAGs were screened. Using Cox regression and Lasso regression analyses for the training group, 5 prognostic AAGs were identified and the prognostic model was constructed. Patients with low risk had better overall survival (OS) in the training group (3-year OS, 73.0% vs 48.0%; 5-year OS, 45.0% vs 33.8%; P = 1.305E-04) and in the testing group (3-year OS, 66.8% vs 41.2%; 5-year OS, 31.7% vs 25.8%; P = 1.027E-03). The areas under the ROC curves (AUC) were significant for both the training and testing groups (3-year AUC, 0.810 vs 0.894; 5-year AUC, 0.792 vs 0.749).
We developed a survival model for LUAD and validated the performance of the model, which may provide superior outcomes for the patients.
Isoprene significantly contributes to organic aerosol in the southeastern United States where biogenic hydrocarbons mix with anthropogenic emissions. In this work, the Community Multiscale Air ...Quality model is updated to predict isoprene aerosol from epoxides produced under both high- and low-NO x conditions. The new aqueous aerosol pathways allow for explicit predictions of two key isoprene-derived species, 2-methyltetrols and 2-methylglyceric acid, that are more consistent with observations than estimates based on semivolatile partitioning. The new mechanism represents a significant source of organic carbon in the lower 2 km of the atmosphere and captures the abundance of 2-methyltetrols relative to organosulfates during the simulation period. For the parametrization considered here, a 25% reduction in SO x emissions effectively reduces isoprene aerosol, while a similar reduction in NO x leads to small increases in isoprene aerosol.
The switch from anchorage-dependent to anchorage-independent growth is essential for epithelial metastasis. The underlying mechanism, however, is not fully understood. In this study, we identified ...growth factor independent-1 (GFI1), a transcription factor that drives the transition from adherent endothelial cells to suspended hematopoietic cells during hematopoiesis, as a critical regulator of anchorage independence in lung cancer cells. GFI1 elevated the numbers of circulating and lung-infiltrating tumor cells in xenograft models and predicted poor prognosis of patients with lung cancer. Mechanistically, GFI1 inhibited the expression of multiple adhesion molecules and facilitated substrate detachment. Concomitantly, GFI1 reconfigured the chromatin structure of the RASGRP2 gene and increased its expression, causing Rap1 activation and subsequent sustained ERK activation upon detachment, and this led to ERK signaling dependency in tumor cells. Our studies unveiled a mechanism by which carcinoma cells hijacked a hematopoietic factor to gain anchorage independence and suggested that the intervention of ERK signaling may suppress metastasis and improve the therapeutic outcome of patients with GFI1-positive lung cancer.
Acid-catalyzed multiphase chemistry of isoprene epoxydiols (IEPOX) on sulfate aerosol produces substantial amounts of water-soluble secondary organic aerosol (SOA) constituents, including ...2-methyltetrols, methyltetrol sulfates, and oligomers thereof in atmospheric fine particulate matter (PM2.5). These constituents have commonly been measured by gas chromatography interfaced to electron ionization mass spectrometry (GC/EI-MS) with prior derivatization or by reverse-phase liquid chromatography interfaced to electrospray ionization high-resolution mass spectrometry (RPLC/ESI-HR-MS). However, both techniques have limitations in explicitly resolving and quantifying polar SOA constituents due either to thermal degradation or poor separation. With authentic 2-methyltetrol and methyltetrol sulfate standards synthesized in-house, we developed a hydrophilic interaction liquid chromatography (HILIC)/ESI-HR-quadrupole time-of-flight mass spectrometry (QTOFMS) protocol that can chromatographically resolve and accurately measure the major IEPOX-derived SOA constituents in both laboratory-generated SOA and atmospheric PM2.5. 2-Methyltetrols were simultaneously resolved along with 4-6 diastereomers of methyltetrol sulfate, allowing efficient quantification of both major classes of SOA constituents by a single non-thermal analytical method. The sum of 2-methyltetrols and methyltetrol sulfates accounted for approximately 92%, 62%, and 21% of the laboratory-generated β-IEPOX aerosol mass, laboratory-generated δ-IEPOX aerosol mass, and organic aerosol mass in the southeastern U.S., respectively, where the mass concentration of methyltetrol sulfates was 171-271% the mass concentration of methyltetrol. Mass concentrations of methyltetrol sulfates were 0.39 and 2.33 μg m-3 in a PM2.5 sample collected from central Amazonia and the southeastern U.S., respectively. The improved resolution clearly reveals isomeric patterns specific to methyltetrol sulfates from acid-catalyzed multiphase chemistry of β- and δ-IEPOX. We also demonstrate that conventional GC/EI-MS analyses overestimate 2-methyltetrols by up to 188%, resulting (in part) from the thermal degradation of methyltetrol sulfates. Lastly, C5-alkene triols and 3-methyltetrahydrofuran-3,4-diols are found to be largely GC/EI-MS artifacts formed from thermal degradation of 2-methyltetrol sulfates and 3-methyletrol sulfates, respectively, and are not detected with HILIC/ESI-HR-QTOFMS.
The human gut microbiome can be easily disturbed upon exposure to a range of toxic environmental agents. Environmentally induced perturbation in the gut microbiome is strongly associated with human ...disease risk. Functional gut microbiome alterations that may adversely influence human health is an increasingly appreciated mechanism by which environmental chemicals exert their toxic effects. In this review, we define the functional damage driven by environmental exposure in the gut microbiome as gut microbiome toxicity. The establishment of gut microbiome toxicity links the toxic effects of various environmental agents and microbiota-associated diseases, calling for more comprehensive toxicity evaluation with extended consideration of gut microbiome toxicity.
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