Purine metabolism in lung adenocarcinoma: A single-cell analysis revealing prognostic and immunotherapeutic insights.

Lung adenocarcinoma (LUAD) is a prevalent subtype of lung cancer, yet the contribution of purine metabolism (PM) to its pathogenesis remains poorly elucidated. PM, a critical component of intracellular nucleotide synthesis and energy metabolism, is hypothesized to exert a significant influence on LUAD development. Herein, we employed single-cell analysis to investigate the role of PM within the tumour microenvironment (TME) of LUAD. PM scoring (PMS) across distinct cell types was determined using AUCell, UCell, singscore and AddModuleScore algorithms. Subsequently, we explored communication networks among cells within high- and low-PMS groups, establishing a robust PM-associated signature (PAS) utilizing a comprehensive dataset comprising LUAD samples from TCGA and five GEO datasets. Our findings revealed that the high-PMS group exhibited intensified cell interactions, while the PAS, constructed using PM-related genes, demonstrated precise prognostic predictive capability. Notably, analysis across the TCGA dataset and five GEO datasets indicated that low-PAS patients exhibited a superior prognosis. Furthermore, the low-PAS group displayed increased immune cell infiltration and elevated CD8A expression, coupled with reduced PD-L1 expression. Moreover, data from eight publicly available immunotherapy cohorts suggested enhanced immunotherapy outcomes in the low-PAS group. These results underscore a close association between PAS and tumour immunity, offering predictive insights into genomic alterations, chemotherapy drug sensitivity and immunotherapy responses in LUAD. The newly established PAS holds promise as a valuable tool for selecting LUAD populations likely to benefit from future clinical stratification efforts.

Integrating machine learning and single-cell analysis to uncover lung adenocarcinoma progression and prognostic biomarkers.

The progression of lung adenocarcinoma (LUAD) from atypical adenomatous hyperplasia (AAH) to invasive adenocarcinoma (IAC) involves a complex evolution of tumour cell clusters, the mechanisms of which remain largely unknown. By integrating single-cell datasets and using inferCNV, we identified and analysed tumour cell clusters to explore their heterogeneity and changes in abundance throughout LUAD progression. We applied gene set variation analysis (GSVA), pseudotime analysis, scMetabolism, and Cytotrace scores to study biological functions, metabolic profiles and stemness traits. A predictive model for prognosis, based on key cluster marker genes, was developed using CoxBoost and plsRcox (CPM), and validated across multiple cohorts for its prognostic prediction capabilities, tumour microenvironment characterization, mutation landscape and immunotherapy response. We identified nine distinct tumour cell clusters, with Cluster 6 indicating an early developmental stage, high stemness and proliferative potential. The abundance of Clusters 0 and 6 increased from AAH to IAC, correlating with prognosis. The CPM model effectively distinguished prognosis in immunotherapy cohorts and predicted genomic alterations, chemotherapy drug sensitivity, and immunotherapy responsiveness. Key gene S100A16 in the CPM model was validated as an oncogene, enhancing LUAD cell proliferation, invasion and migration. The CPM model emerges as a novel biomarker for predicting prognosis and immunotherapy response in LUAD patients, with S100A16 identified as a potential therapeutic target.

Deciphering lung adenocarcinoma evolution: Integrative single-cell genomics identifies the prognostic lung progression associated signature.

We employed single-cell analysis techniques, specifically the inferCNV method, to dissect the complex progression of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) through minimally invasive adenocarcinoma (MIA) to invasive adenocarcinoma (IAC). This approach enabled the identification of Cluster 6, which was significantly associated with LUAD progression. Our comprehensive analysis included intercellular interaction, transcription factor regulatory networks, trajectory analysis, and gene set variation analysis (GSVA), leading to the development of the lung progression associated signature (LPAS). Interestingly, we discovered that the LPAS not only accurately predicts the prognosis of LUAD patients but also forecasts genomic alterations, distinguishes between 'cold' and 'hot' tumours, and identifies potential candidates suitable for immunotherapy. PSMB1, identified within Cluster 6, was experimentally shown to significantly enhance cancer cell invasion and migration, highlighting the clinical relevance of LPAS in predicting LUAD progression and providing a potential target for therapeutic intervention. Our findings suggest that LPAS offers a novel biomarker for LUAD patient stratification, with significant implications for improving prognostic accuracy and guiding treatment decisions.

Clinical prognostication and immunotherapy response prediction in esophageal squamous cell carcinoma using the DNA damage repair-associated signature.

BACKGROUND: The relationship between DNA damage repair (DDR) and cancer is intricately intertwined; however, its specific role in esophageal squamous cell carcinoma (ESCC) remains enigmatic. METHODS: Employing single-cell analysis, we delineated the functionality of DDR-related genes within the tumor microenvironment (TME). A diverse array of scoring mechanisms, including AUCell, UCell, singscore, ssgsea, and AddModuleScore, were harnessed to scrutinize the activity of DDR-related genes across different cell types. Differential pathway alterations between high-and low-DDR activity cell clusters were compared. Furthermore, leveraging multiple RNA-seq datasets, we constructed a robust DDR-associated signature (DAS), and through integrative multiomics analysis, we explored differences in prognosis, pathways, mutational landscapes, and immunotherapy predictions among distinct DAS groups. RESULTS: Notably, high-DDR activity cell subpopulations exhibited markedly enhanced cellular communication. The DAS demonstrated uniformity across multiple datasets. The low-DAS group exhibited improved prognoses, accompanied by heightened immune infiltration and elevated immune checkpoint expression. SubMap analysis of multiple immunotherapy datasets suggested that low-DAS group may experience enhanced immunotherapy responses. The "oncopredict" R package analyzed and screened sensitive drugs for different DAS groups. CONCLUSION: Through the integration of single-cell and bulk RNA-seq data, we have developed a DAS associated with prognosis and immunotherapy response. This signature holds promise for the future stratification and personalized treatment of ESCC patients in clinical settings.

miR-423-3p activates FAK signaling pathway to drive EMT process and tumor growth in lung adenocarcinoma through targeting CYBRD1.

BACKGROUND: Lung adenocarcinoma (LUAD) is a malignant tumor with a high fatality rate and poor overall survival, while molecular targets diagnosing and alleviating lung cancer remain inadequate. METHODS: In this article, we highlighted the upregulation of microRNA-423-3p (miR-423-3p) in LUAD, especially in smokers aged over 40, and revealed that the high expression of miR-423-3p was significantly associated with smoker, age, and pathologic stage of LUAD patients. RESULTS: Moreover, overexpressing miR-423-3p could facilitate LUAD cell proliferation, invasion, adhesion, and epithelial-mesenchymal transition (EMT) process, while depleted miR-423-3p caused repressive influence upon it. Mechanically, we identified that miR-423-3p could activate FAK signaling pathway through binding to the 3'-UTR of cytochrome B reductase 1 (CYBRD1). Furthermore, we demonstrated that CYBRD1 was lowly expressed in LUAD, and miR-423-3p overexpression could rescue the impairment of LUAD cell proliferation, invasion, adhesion, and EMT caused by CYBRD1 depletion. Noticeably, miR-423-3p depletion efficiently hindered LUAD tumor growth in vivo. CONCLUSION: Collectively, our findings demonstrated that miR-423-3p/CYBRD1 axis could be regarded as a promising biomarker to alleviate the poor LUAD prognosis.

Nomogram based on homogeneous and heterogeneous associated factors for predicting bone metastases in patients with different histological types of lung cancer.

BACKGROUND: The purpose of the present study was to characterize the prevalence, associated factors, and to construct a nomogram for predicting bone metastasis (BM) with different histological types of lung cancer. PATIENTS AND METHODS: This study was a descriptive study that basing on the invasive lung cancer patients diagnosed between 2010 and 2014 in Surveillance, Epidemiology, and End Results program. A total of 125,652 adult patients were retrieved. Logistic regression analysis was conducted to investigate homogeneous and heterogeneous factors for BM occurrence. Nomogram was constructed to predict the risk for developing BM and the performance was evaluated by the receiver operating characteristics curve (ROC) and the calibration curve. The overall survival of the patients with BM was analyzed using the Kaplan-Meier method and the survival differences were tested by the log-rank test. RESULTS: A total of 25,645 (20.9%) were reported to have BM, and the prevalence in adenocarcinoma, squamous cell carcinoma, small cell lung cancer (SCLC), large cell lung cancer (LCLC), and non-small cell lung cancer/not otherwise specified lung cancer (NSCLC/NOS) were 24.4, 12.5, 24.7, 19.5 and 19.4%, respectively, with significant difference (P < 0.001). Male gender, more metastatic sites and lymphatic metastasis were positively associated with BM in all lung cancer subtypes. Larger tumor size was positively associated with BM in all the lung cancer subtypes except for NSCLC/NOS. Poorly differentiated histology was positively associated with adenocarcinoma, squamous cell carcinoma and NSCLC/NOS. The calibration curve and ROC curve exhibited good performance for predicting BM. The median survival of the bone metastatic lung cancer patients was 4.00 (95%CI: 3.89-4.11) months. With the increased number of the other metastatic sites (brain, lung and liver metastasis), the survival significantly decreased (p < 0.001). CONCLUSION: Different lung cancer histological subtypes exhibited distinct prevalence and homogeneity and heterogeneity associated factors for BM. The nomogram has good calibration and discrimination for predicting BM of lung cancer.

[Cetuximab in combination with icotinib overcomes the acquired resistance caused by EGFR T790M mutation in non-small cell lung cancer].

OBJECTIVE: The aim of this study was to investigate the effects of combination of icotinib and cetuximab on the acquired drug resistance caused by T790M mutation of EGFR in NSCLC, and provide experimental evidence for rational treatment of NSCLC. METHODS: The effects of these two agents on cell proliferation, apoptosis, and EGFR-dependent signaling were evaluated using 3-(4, 5-dimethylthiazol-2-yl)- 5-diphenyltetrazolium bromide (MTT) assay, annexin V staining, and Western blotting. The expression of molecular markers of tumor proliferation PCNA and Ki-67 protein was further examined by immunohistochemistry, and the expression of EGFR-signaling-related proteins in tissue sections taken from H1975 tumor xenografts was assessed by Western blot assay. Sensitivity to EGFR inhibitors was detected in human H1975 tumor xenograft in nude mice. RESULTS: The in vitro experiment showed that the proliferative ability of H1975 cells was inhibited in a dose-dependent manner, along with the increasing doses of cetuximab and icotinib, and the combination of cetuximab with icotinib resulted in a more pronounced growth inhibition of the H1975 cells. The apoptosis rate of H1975 cells after treatment with 0.5 µmol/L icotinib and 1 µg/ml cetuximab was (22.03 ± 2.41)% and that after treatment with 5 µmol/L icotinib and 10 µg/ml cetuximab was (42.75 ± 2.49)%, both were significantly higher than that after treatment with the same dose of icotinib or cetuximab alone (P < 0.05). The nude mouse experiment showed that the transplanted tumor was growing to (614.5 ± 10.8) mm(3) in the blank control group and to (611.2 ± 8.7) mm(3) at 28 days after icotinib treatment, but (30.8 ± 2.0) mm(3) in the cetuximab treatment group and 0 mm(3) in the cetuximab combined with icotinib group. There was a significantly decreased expression of Ki-67 and PCNA proteins and down-regulation of phosphorylation of EGFR signaling-related proteins in the cetuximab combined with icotinib group. CONCLUSIONS: The combination of icotinib with cetuximab can exert synergistic inhibitory effect on the acquired drug resistance caused by T790M mutation of EGFR in NSCLC H1975 cells, interrupts the EGFR-downstream signaling pathway, and enhances the anticancer activity of chemotherapeutic drugs. Our results provide further experimental evidence for the clinical studies of combination of icotinib with cetuximab in the treatment of NSCLC patients associated with secondary drug resistance caused by T790M mutation of EGFR.

Exploring cellular diversity in lung adenocarcinoma epithelium: Advancing prognostic methods and immunotherapeutic strategies.

Immunotherapy has brought significant advancements in the treatment of lung adenocarcinoma (LUAD), but identifying suitable candidates remains challenging. In this study, we investigated tumour cell heterogeneity using extensive single-cell data and explored the impact of different tumour cell cluster abundances on immunotherapy in the POPLAR and OAK immunotherapy cohorts. Notably, we found a significant correlation between CKS1B+ tumour cell abundance and treatment response, as well as stemness potential. Leveraging marker genes from the CKS1B+ tumour cell cluster, we employed machine learning algorithms to establish a prognostic and immunotherapeutic signature (PIS) for LUAD. In multiple cohorts, PIS outperformed 144 previously published signatures in predicting LUAD prognosis. Importantly, PIS reliably predicted genomic alterations, chemotherapy sensitivity and immunotherapy responses. Immunohistochemistry validated lower expression of immune markers in the low-PIS group, while in vitro experiments underscored the role of the key gene PSMB7 in LUAD progression. In conclusion, PIS represents a novel biomarker facilitating the selection of suitable LUAD patients for immunotherapy, ultimately improving prognosis and guiding clinical decisions.

Deciphering the prognostic role of endoplasmic reticulum stress in lung adenocarcinoma: integrating prognostic prediction and immunotherapy strategies.

Endoplasmic reticulum stress (ERS) is a critical factor influencing lung adenocarcinoma (LUAD) progression and patient outcomes. In this study, we analyzed gene expression data from LUAD samples sourced from The Cancer Genomic Atlas and Gene Expression Omnibus databases. Utilizing advanced statistical methods including LASSO and Cox regression, we developed a ERS-associated signature (ERAS) based on ten ERS-related genes. This model stratified patients into high- and low-risk groups, with the high-risk group exhibiting decreased survival rates, elevated tumor mutational burden, and heightened chemotherapy sensitivity. Additionally, we observed lower immune and ESTIMATE scores in the high-ERAS group, indicating a potentially compromised immune response. Experimental validation through quantitative real-time polymerase chain reaction confirmed the utility of our model. Furthermore, we constructed a nomogram to predict 1-, 3-, and 5-year survival rates, providing clinicians with a valuable tool for personalized patient management. In conclusion, our study demonstrates the efficacy of the ERAS in identifying high-ERAS LUAD patients, offering promising implications for improved prognostication and treatment strategies.

Cavitation erosion-corrosion properties of as-cast TC4 and LPBF TC4 in 0.6 mol/L NaCl solution: A comparison investigation.

In this work study, a comparative analysis was undertaken to investigate investigation into the cavitation erosion (CE) and corrosion behavior of laser powder bed fusion (LPBF) TC4 and as-cast TC4 in 0.6 mol/L NaCl solution. Relevant results indicated that LPBF TC4 revealed a rectangular checkerboard-like pattern with a more refined grain size compared to as-cast TC4. Meanwhile, LPBF TC4 surpassed its as-cast counterpart in CE resistance, demonstrating approximately 2.25 times lower cumulative mass loss after 8 h CE. The corrosion potential under alternating CE and quiescence conditions demonstrated that both LPBF TC4 and as-cast TC4 underwent a rapid potential decrease at the initial stages of CE, while a consistent negative shift in corrosion potential was observed with the continuously increasing CE time, indicative of a gradual decline in repassivation ability. The initial surge in corrosion potential during the early CE stages was primarily attributed to accelerated oxygen transfer. As CE progressed, the significant reduction in corrosion potential for both LPBF TC4 and as-cast TC4 was attributed to the breakdown of the passive film. The refined and uniform microstructure in LPBF TC4 effectively suppresses both crack formation and propagation, underscoring the potential of LPBF technology in enhancing the CE resistance of titanium alloys. This work can provide important insights into developing high-quality, reliable, and sustainable CE-resistant materials via LPBF technology.

Exploring clinical factors to predict the survival for resectable non-small cell lung cancer patients with neoadjuvant immunotherapy.

OBJECTIVES: To explore clinical factors and build a predictive model for the disease-free and overall survival in non-small cell lung cancer patients receiving neoadjuvant chemotherapy combined with immune checkpoint inhibitors. METHODS: Inclusion criteria for patients in this multicentre study were: (1) patients were diagnosed with stage I-III non-small cell lung cancer diagnosed by bronchoscopy biopsy or puncture; (2) computed tomography/positron emission tomography-computed tomography was applied before treatment and surgery; (3) neoadjuvant chemotherapy combined with immune checkpoint inhibitors were applied for 2-6 cycles preoperatively; (4) peripheral blood indicators and tumour markers were assessed before treatment and surgery; (5) patients underwent radical lung cancer surgery after neoadjuvant therapy. Cases were divided into high- and low-risk groups according to 78 clinical indicators based on 10-fold LASSO selection. We employed Cox proportional hazards models in predicting disease-free and overall survival. Then, we used time-dependent area under the curve and decision curve analyses to examine the accuracy of the results. RESULTS: Data were collected continuously, and 212 and 85 cases were randomly assigned to training and testing sets, respectively. The area under curve for the prediction of disease-free survival (training-1-year, 0.83; 2-year, 0.81; 3-year, 0.83 vs testing-1-year, 0.65; 2-year, 0.66; 3-year, 0.70), overall survival (training-1-year, 0.86; 2-year, 0.85; 3-year, 0.86 vs testing-1-year, 0.66; 2-year, 0.57; 3-year, 0.70) were determined. The coefficient factors including pathological response, preoperative tumour maximum diameter, preoperative lymph shorter-diameter, preoperative tumour&lymph maximum standardized uptake value, change in tumour standardized uptake value preoperative, and blood related risk factors were favorably associated with prognosis (P < 0.001). CONCLUSIONS: Our prediction model integrating data from preoperative positron emission tomography-CT, preoperative blood parameters, and pathological response was able to make high accuracy predictions for disease-free and overall survival in non-small cell lung cancer patients receiving neoadjuvant immunity with chemical therapy.

Study on cavitation erosion-corrosion behavior of CoCrFeNiMoCu0.1 high entropy alloy in 3.5 wt% NaCl solution.

The challenge of cavitation erosion (CE) in flow-handling components of marine engineering has promoted the development of advanced materials due to safety incidents and economic costs. High entropy alloys (HEAs), known for high hardness and corrosion resistance, emerge as promising candidates. This paper delved into the CE characteristics of CoCrFeNiMoCu0.1 HEA when subjected to the 3.5 wt% NaCl solution, elucidating the synergistic effect of CE-corrosion. The quantitative analysis revealed that CE-corrosion synergy contributed 48.02% to total CE mass loss, primarily attributed to corrosion-induced CE damage. Meanwhile, electrochemical noise (EN) was utilized to reveal the corrosion behavior of CoCrFeNiMoCu0.1 HEA in 3.5 wt% NaCl solution combined with the morphologies observation and surface roughness. Extended CE time compromised the corrosion resistance of CoCrFeNiMoCu0.1 HEA and diminished the impact of selective phase corrosion on the surface. Eventually, the CE damage mechanism of CoCrFeNiMoCu0.1 HEA was revealed based on pertinent experimental findings. The results showed that with increased CE time, the CoCrFeNiMoCu0.1 HEA transitioned from predominantly extensive exfoliation of the initial FCC phase to further damage of the intermetallic σ and µ phases.

[Retracted] lncRNA­u50535 promotes the progression of lung cancer by activating CCL20/ERK signaling.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the western blotting data shown in Fig. 4B and C on p. 1952, and the Transwell invasion assay data in Fig. 2F and 4I, had already appeared in previously published articles written by different authors at different research institutes (a number of which have been retracted). Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 42: 1946­1956, 2019; DOI: 10.3892/or.2019.7302].

A cuproptosis-related lncRNA signature-based prognostic model featuring on metastasis and drug selection strategy for patients with lung adenocarcinoma.

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.

Understanding the Corrosion Behavior of Nickel-Aluminum Bronze Induced by Cavitation Corrosion Using Electrochemical Noise: Selective Phase Corrosion and Uniform Corrosion.

Nickel-aluminum bronze (NAB) is widely used to fabricate flow-handling components because of its good cavitation corrosion (CE) resistance and superior casting property. The existence of different phases, e.g., the α phase, ß phase and κ phase, can cause significant selective phase corrosion on NAB. However, under the action of CE with different times, the influence of these phases on the corrosion behavior of NAB, including selective phase corrosion and uniform corrosion, needs to be further studied, which can contribute to a deep understanding of the CE mechanism of NAB in corrosive media. In this work, the corrosion behavior of NAB in 3.5 wt.% NaCl solution after different CE times was evaluated by electrochemical noise (EN), combined with scanning Kelvin probe force microscopy (SKPFM) and morphology analysis. The results showed that the corrosion behavior of NAB was closely associated with the variation in its complex microstructure after different CE times. Selective phase corrosion played a crucial role in the surface damage before 0.5 h of CE. With the prolongation of CE time, the stripping of κ phases decreased the degree of selective phase corrosion of NAB. As a result, both selective phase corrosion and uniform corrosion presented equal performances after 1 h of CE. However, after CE for 2-5 h, uniform corrosion had a dominant impact on the surface damage of NAB. Eventually, the corrosion mechanism of NAB after different CE times was clarified based on the relevant experimental results.

Ion channel gene GJB2 influences the intercellular communication by Up-regulating the SPP1 signaling pathway identified by the single-cell RNA sequencing in lung adenocarcinoma.

Objective: Firstly, observe the prognostic significance and the biological functional effects of gap junction protein beta 2 (GJB2 or Cx26) in lung adenocarcinoma (LUAD). Subsequently, explore the role played by GJB2 in intercellular communication by single-cell RNA sequencing. Method: We made a differential analysis of GJB2 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 GJB2 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 GJB2. Cell-cell communication was analyzed using the CellChat R package through sc-RNA data. Results: GJB2 has an outstanding prognosis value in LUAD and a close relationship was found between GJB2 and immune infiltration in LUAD. GJB2 could participate in several tumor biological processes, including extracellular matrix remodeling and upregulation of multiple cancer-related active pathways. GJB2 related hub-genes influence intercellular communication through the SPP1 signaling pathway. Conclusion: Our study illustrates one mechanism by which GJB2 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 GJB2 and provide us with promising new perceptions for LUAD treatment.

CT-based radiomics model to predict spread through air space in resectable lung cancer.

BACKGROUND: Spread through air space (STAS) has been identified as a pathological pattern associated with lung cancer progression. Patients with STAS were related to a worse prognosis compared with patients without STAS. The objective of this study was to establish a radiomics model capable of forecasting STAS before surgery, which can assist surgeons in selecting the most appropriate operation type for patients with STAS. METHOD: There were 537 eligible patients retrospectively included in this study. ROI segmentation was performed manually on all CT images to identify the region of interest. From each segmented lesion, a total of 1688 features were extracted. The tumor size, maximum tumor diameters, and tumor type were also recorded. Using Spearman's correlation coefficient to calculate the correlation and redundancy of elements, and redundant features less than 0.80 were removed. In order to reduce the level of overfitting and avoid statistical biases, a dimension reduction process of the dataset was conducted to decrease the number of features. Finally, a radiomics model included 44 features was established to predict STAS. To evaluate the performance of the model, the receiver operating characteristic (ROC) curve was used, and the area under the curve (AUC) was calculated, and the accuracy of the model was verified by 10-fold cross-validation. RESULTS: The incidence of STAS was 38.2% (205/537). The tumor type, maximum tumor diameters, and consolidation tumor ratio were significantly different between STAS group and non-STAS group. The training group included 430 patients, while the test group was consisted with 107. The training group achieved an AUC of 0.825 (sensitivity, 0.875; specificity, 0.621; and accuracy, 0.749) and the test group had an AUC of 0.802 (sensitivity, 0.797; specificity,0.688; and accuracy, 0.748). The 10-fold cross-validation had an AUC of 0.834. CONCLUSION: CT-based radiomic model can predict STAS effectively, which is of great importance to guide the selection of operation types before surgery.

Effects of cavitation erosion-induced surface damage on the corrosion behaviour of TA31 Ti alloy.

This study used electrochemical noise technology to analyse the effects of surface damage induced by cavitation erosion (CE) on the pitting and passivation behaviours of TA31 Ti alloy. According to the results, TA31 Ti alloy exhibited high corrosion resistance in NaCl solutions. However, the residual tensile stress layer generated during grinding and polishing reduced its passivation ability. Subsequently, the residual tensile stress layer was eliminated after CE for 1 h, improving the passivation ability of the material. Thereafter, pitting corrosion was initiated on the material surface. Increasing the CE time from 1 h to 2 h gradually decreased the passivation ability of the alloy. A large number of CE holes promoted the transition from pitting initiation to metastable pitting growth. which gradually dominated the surface of TA31 Ti alloy. The damage mechanism of uniform thinning increased the passivation ability and stability of the alloy with the increase in CE time from 2 h to 6 h. Therefore, the surface of TA31 Ti alloy was dominated by the initiation of pitting corrosion.

Value of the metastatic lymph node ratio for predicting the prognosis of non-small-cell lung cancer patients.

BACKGROUND: The aim of this study was to investigate the relation between the metastatic lymph node ratio (LNR) and the prognosis of non-small-cell lung cancer (NSCLC). METHODS: A total of 301 patients with N1 or N2 NSCLC who underwent complete pulmonary resection were analyzed retrospectively. The correlations between the LNR and clinical and pathologic data were analyzed using χ(2) test analysis. The prognostic value of the LNR was calculated by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis. The risk groups were classified by a combination of the LNR and pN stage. RESULTS: The LNR was correlated with age, smoking status, pathologic type, subcarinal lymph node, clinical staging, N stage (P < 0.05), and the number of positive lymph nodes and positive lymph node stations (P < 0.0001). In the univariate analysis, the LNR played an important role in predicting overall survival (OS) (P < 0.0001) and disease-free survival (P < 0.0001) by Kaplan-Meier survival analysis. In the multivariate analysis, high LNR (>18%) was an independent poor prognostic factor for OS [hazard ratio (HR) 2.5034, 95% confidence interval (CI) 1.6096-3.8933, P < 0.0001] and DFS (HR 1.9023, 95% CI 1.2465-2.9031, P = 0.0031). Stratification into high-, medium-, and low-risk groups-based on high-risk factors (LNR > 18%, N2) intermediate-risk factors (LNR > 18%, N1 or LNR < 18%, N2), and low-risk factors (LNR < 18%, N1)-could efficiently predicted outcomes (P < 0.0001) of patients with lymph node-positive NSCLC. CONCLUSIONS: The combination of the LNR and pN status provides a valuable help with prognosis. However, these results must be evaluated further in a large prospective randomized clinical trial.

[Diagnostic value of (18)F-FDG PET/CT imaging plus serum tumor marker assays for pulmonary lesions and clinical significance of SUVmax].

OBJECTIVE: To evaluate the diagnostic value of (18)F-FDG positron emission tomography/computed tomography (PET/CT) plus serum tumor marker assay in lung cancer and explore the correlation between standard uptake value (SUVmax) with clinicopathologic factors in lung cancer. METHODS: A total of 177 cases of lung cancer diagnosed by radiography or computed tomography (CT) were recruited.(18)F-FDG PET/CT imaging and detection of three lung cancer related serum markers (carcinoembryonic antigen, CYFRA21-1 and neuron specific enolase) were performed within one week in all cases. The sensitivity, specificity and accuracy of those approaches were calculated through comparing the results with pathologic examinations. Also the associations between SUVmax and clinicopathologic features were analyzed. RESULTS: Among them, 145 patients were detected to have lung cancer by pathologic diagnosis while the other 32 patients had benign lung diseases. The sensitivity, specificity, accuracy of (18)F-FDG PET/CT imaging, serum tumor markers and their combination in assessing lung cancers were 89.7%, 78.1%, 87.6%; 89.7%, 78.1%, 87.6% and 96.6%, 56.3%, 89.3% respectively. The combination of (18)F-FDG PET/CT and serum tumor markers in lung lesions showed significantly higher sensitivity than serum tumor markers and (18)F-FDG PET/CT alone (P = 0.000, P = 0.002). Its accuracy was also significantly higher than those of tumor markers (P < 0.05). Compared with (18)F-FDG PET/CT alone, the accuracy was higher in combination group. But the difference showed no statistical significance (P > 0.05). SUVmax was significantly associated with tumor staging, tumor size and pathologic type. CONCLUSION: The combination of (18)F-FDG PET/CT and tumor markers may improve the positive diagnostic rate of lung cancer. And SUVmax can help to evaluate tumor staging and determine pathological types.