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Abstract The clinical translation of tumor hypoxia intervention modalities still falls short of expectation, restricted by poor biocompatibility of oxygen‐carrying materials, unsatisfactory oxygen loading performance, and abnormally high cellular oxygen consumption‐caused insufficient hypoxia relief. Herein, a carrier‐free oxygen nano‐tank based on modular fluorination prodrug design and co‐assembly nanotechnology is elaborately exploited, which is facilely fabricated through the molecular nanoassembly of a fluorinated prodrug (FSSP) of pyropheophorbide a (PPa) and an oxygen consumption inhibitor (atovaquone, ATO). The nano‐tank adeptly achieves sufficient oxygen enrichment while simultaneously suppressing oxygen consumption within tumors for complete tumor hypoxia alleviation. Significant, the fluorination module in FSSP not only confers favorable co‐assemblage of FSSP and ATO, but also empowers the nanoassembly to readily carry oxygen. As expected, it displays excellent oxygen carrying capacity, favorable pharmacokinetics, on‐demand laser‐triggerable ATO release, closed‐loop tumor hypoxia relief, and significant enhancement to PPa‐mediated PDT in vitro and in vivo. This study provides a novel nanotherapeutic paradigm for tumor hypoxia intervention‐enhanced cancer therapy.

Endometrial cancer (EC) is one of the most common gynecologic malignancies with increasing morbidity. The prognosis for patients diagnosed with early-stage EC remains favorable; however, for patients with recurrent or metastatic EC, the prognosis is poor and treatment options, until recently, are limited. Antibody drug conjugates (ADCs) represent innovative strategies in cancer treatment; however, there are less investigations regarding their efficacy in EC. This report describes an EC case with low human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) expression score (IHC 2+) that experienced recurrent metastasis in the abdominal and peritoneal following post-surgical chemotherapy and radiotherapy. Subsequently, the commencement of HER2-targeted ADC, disitamab vedotin (RC48; 2.5 mg/kg), administered intravenously every two weeks, was initiated. The tumor lesions shrunk markedly after three cycles of treatment and disappeared by the completion of ten cycles of therapy. The patient is still in remission at present. The current findings imply the potential efficacy of HER2-targeted ADCs for patients with HER2-low metastatic EC.

Abstract Background Emerging data suggested a favorable outcome in advanced non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) patients treated by immunotherapy. The objective of this study was to investigate the effectiveness of neoadjuvant immunotherapy among NSCLC with COPD versus NSCLC without COPD and explore the potential mechanistic links. Patients and methods Patients with NSCLC receiving neoadjuvant immunotherapy and surgery at Shanghai Pulmonary Hospital between November 2020 and January 2023 were reviewed. The assessment of neoadjuvant immunotherapy’s effectiveness was conducted based on the major pathologic response (MPR). The gene expression profile was investigated by RNA sequencing data. Immune cell proportions were examined using flow cytometry. The association between gene expression, immune cells, and pathologic response was validated by immunohistochemistry and single-cell data. Results A total of 230 NSCLC patients who received neoadjuvant immunotherapy were analyzed, including 60 (26.1%) with COPD. Multivariate logistic regression demonstrated that COPD was a predictor for MPR after neoadjuvant immunotherapy [odds ratio (OR), 2.490; 95% confidence interval (CI), 1.295–4.912; P = 0.007]. NSCLC with COPD showed a down-regulation of HERV–H LTR-associating protein 2 (HHLA2), which was an immune checkpoint molecule, and the HHLA2low group demonstrated the enrichment of CD8+CD103+ tissue-resident memory T cells (TRM) compared to the HHLA2high group (11.9% vs. 4.2%, P = 0.013). Single-cell analysis revealed TRM enrichment in the MPR group. Similarly, NSCLC with COPD exhibited a higher proportion of CD8+CD103+TRM compared to NSCLC without COPD (11.9% vs. 4.6%, P = 0.040). Conclusions The study identified NSCLC with COPD as a favorable lung cancer type for neoadjuvant immunotherapy, offering a new perspective on the multimodality treatment of this patient population. Down-regulated HHLA2 in NSCLC with COPD might improve the MPR rate to neoadjuvant immunotherapy owing to the enrichment of CD8+CD103+TRM. Trial registration Approval for the collection and utilization of clinical samples was granted by the Ethics Committee of Shanghai Pulmonary Hospital (Approval number: K23-228).

Abstract Objective This study assessed the outcomes of elderly patients with limited‐stage small cell lung cancer (LS‐SCLC), which may be linked to the timing of thoracic radiotherapy (TRT) following chemotherapy. Methods Elderly patients (n = 78) with LS‐SCLC were divided into three groups depending on the timing of radiotherapy. The patients in the TRT group were stratified into early (TRT after 1–2 cycles of chemotherapy, n = 29), medium‐term (TRT after 3–4 cycles of chemotherapy, n = 33), and late (TRT after 5–6 cycles of chemotherapy, n = 16) TRT groups. The overall survival (OS) and progression‐free survival (PFS) were assessed and compared. Results The medium‐term TRT group demonstrated significantly longer mPFS (20.12 months) and better mOS (35.97 months) than those in the other groups (PFS: P = 0.021;OS: P = 0.035). A pairwise comparison of the three groups revealed that those who received medium‐term TRT exhibited significantly improved PFS than the early (mPFS: 20.12 vs. 10.36 mouths, P = 0.018) and late (mPFS: 20.12 vs. 9.17 months, P = 0.016) TRT. The medium‐term TRT group demonstrated significantly improved OS than the early TRT (mOS: 35.97 vs. 25.22 months, P = 0.007) but not in comparison with the late TRT (mOS: 35.97 vs. 21.63 months, P = 0.100). Conclusion In elderly patients with LS‐SCLC, the addition of TRT after 3–4 cycles of chemotherapy appears to be a viable and potentially beneficial treatment approach.

Abstract Lung cancer is a leading cause of cancer deaths and imposes an enormous economic burden on patients. It is important to develop an accurate risk assessment model to determine the appropriate treatment for patients after an initial lung cancer diagnosis. The Cox proportional hazards model is mainly employed in survival analysis. However, real-world medical data are usually incomplete, posing a great challenge to the application of this model. Commonly used imputation methods cannot achieve sufficient accuracy when data are missing, so we investigated novel methods for the development of clinical prediction models. In this article, we present a novel model for survival prediction in missing scenarios. We collected data from 5,240 patients diagnosed with lung cancer at the Weihai Municipal Hospital, China. Then, we applied a joint model that combined a BN and a Cox model to predict mortality risk in individual patients with lung cancer. The established prognostic model achieved good predictive performance in discrimination and calibration. We showed that combining the BN with the Cox proportional hazards model is highly beneficial and provides a more efficient tool for risk prediction.

Lung cancer incidence and mortality rates are increasing worldwide, posing a significant public health challenge and an immense burden to affected families. Lung cancer encompasses distinct subtypes, namely, non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). In clinical investigations, researchers have observed that neuroendocrine tumors can be classified into four types: typical carcinoid, atypical carcinoid, small-cell carcinoma, and large-cell neuroendocrine carcinoma based on their unique features. However, there exist combined forms of neuroendocrine cancer. This study focuses specifically on combined pulmonary carcinomas with a neuroendocrine component. In this comprehensive review article, the authors provide an overview of combined lung cancers and present two pathological images to visually depict these distinctive subtypes.

Summary: Brain metastases (BM) of lung adenocarcinoma (LUAD) are the most common intracranial malignancy leading to death. However, the cellular origins and drivers of BM from LUAD have not been clarified. Cellular composition was characterized by single-cell sequencing analysis of primary lung adenocarcinoma (pLUAD), BM and lymph node metastasis (LNM) samples in GSE131907. Our study briefly analyzed the tumor microenvironment (TME), focusing on the role of epithelial cells (ECs) in BM. We have discovered a population of brain metastasis-associated epithelial cells (BMAECs) expressing SPP1, SAA1, and CDKN2A, and it has been observed that this population is mainly composed of aneuploid cells from pLUAD, playing a crucial role in brain metastasis. Our study concluded that both LNM and BM in LUAD originated from pLUAD lesions, but there is currently insufficient evidence to prove a direct association between BM lesions and LNM lesions, which provides inspiration for further investigation of the TME in BM.

Abstract Small‐cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that is prone to spread extensively. Compared to non‐small‐cell lung cancer (NSCLC), SCLC treatment progresses slowly. Although SCLC is highly sensitive to chemotherapy during the initial treatment, most patients still experience resistance and recurrence after receiving chemotherapy. A meta‐analysis demonstrated that thoracic radiotherapy (TRT) improves overall survival in SCLC. The results of the CALGB and CONVERT trials provide evidence for the efficacy of once‐daily high‐dose TRT. TRT at 60 Gy administered twice daily significantly improved survival without increasing toxicity. The long‐standing debate over the optimal timing of radiotherapy has not been fully resolved. SBRT has excellent local control rates and is a safe and effective treatment option for patients with stage I or II SCLC. Prophylactic cranial irradiation (PCI) is used to reduce treatment‐related neurotoxicity to the extent that there has been a recent discussion on whether magnetic resonance imaging (MRI) monitoring can replace PCI. Radiotherapy combined with immunotherapy significantly improves the survival rate of patients with NSCLC; however, its clinical effectiveness has not been systematically explored in patients with SCLC. Therefore, we summarize the evolving therapeutic strategies, (TRT for limited stage‐SCLC and consolidative TRT for extensive stage‐SCLC) and improved radiotherapy techniques (role of SBRT in stage I or II node‐negative SCLC, progress of PCI, and stereotactic radiosurgery), and discuss the possibilities and prospects of radiotherapy combined with immunotherapy for SCLC.

Objective: To investigate the prognostic factors in and role of postoperative radiotherapy (PORT) for surgically resected thymomas. Methods: A total of 1540 patients with pathologically confirmed thymomas undergoing resection between 2000 and 2018 were identified retrospectively from the SEER (Surveillance, Epidemiology, and End Results) database. Tumors were restaged as local (limited to thymus), regional (invasion to mediastinal fat and other neighboring structures), or distant stage. Disease-specific survival (DSS) and overall survival (OS) were estimated by the Kaplan–Meier method and the log-rank test. Adjusted hazard ratios (HRs) with 95% CIs were calculated by Cox proportional hazards modeling. Results: Tumor stage and histology were independent predictors of both DSS (regional: HR, 3.711; 95% CI, 2.006-6.864; distant: HR, 7.920; 95% CI, 4.061-15.446; type B2/B3: HR, 1.435; 95% CI, 1.008-2.044) and OS (regional: HR, 1.461; 95% CI, 1.139-1.875; distant: HR, 2.551; 95% CI, 1.855-3.509; type B2/B3: HR, 1.409; 95% CI, 1.153-1.723). For patients with regional stage and type B2/B3 thymomas, PORT was associated with better DSS after thymectomy/thymomectomy (HR, 0.268; 95% CI, 0.099-0.727), but the association was not significant after extended thymectomy (HR, 1.514; 95% CI, 0.516-4.44). Among patients with lymph node metastases, those who received PORT (HR, 0.372; 95% CI, 0.146-0.949), chemotherapy (HR, 0.843; 95% CI, 0.303-2.346), or both (HR, 0.296, 95% CI, 0.071-1.236) had a better OS. Conclusions: The extent of invasion and tumor histology were independent predictors of worse survival following surgical resection of thymoma. Patients with regional invasion and type B2/B3 thymoma who undergo thymectomy/thymomectomy may benefit from PORT, while patients with nodal metastases may benefit from multimodal therapy, including PORT and chemotherapy.

With the unprecedented development of big data, it is becoming hard to get the valuable information hence, the recommendation system is becoming more and more popular. When the limited Boltzmann machine is used for collaborative filtering, only the scoring matrix is considered, and the influence of the item content, the user characteristics and the user evaluation content on the predicted score is not considered. To solve this problem, the modified hybrid recommendation algorithm based on Gaussian restricted Boltzmann machine is proposed in the paper. The user text information and the item text information are input to the embedding layer to change the text information into numerical vector. The convolutional neural network is used to get the latent feature vector of the text information. The latent vector is connected to rating vector to get the item and the user vector. The user vector and the item vector are fused together to get the user-item matrix which is input to the visual layer of Gaussian restricted Boltzmann Machine to predict the ratings. Some simulation experiments have been performed on the algorithm, and the results of the experiments proved that the algorithm is feasible.

BackgroundThe purpose of this study was to evaluate the role of differentiation-related genes (DRGs) in tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC).MethodsSingle cell RNA-seq (scRNA-seq) data from GEO and bulk RNA-seq data from TCGA were analyzed to identify DRGs using trajectory method. Functional gene analysis was carried out by GO/KEGG enrichment analysis. The mRNA and protein expression in human tissue were analyzed by HPA and GEPIA databases. To investigate the prognostic value of these genes, three risk score (RS) models in different pathological types of NSCLC were generated and predicted NSCLC prognosis in datasets from TCGA, UCSC and GEO databases.Results1,738 DRGs were identified through trajectory analysis. GO/KEGG analysis showed that these genes were predominantly related to myeloid leukocyte activation and leukocyte migration. 13 DRGs (C1QB, CCL4, CD14, CD84, FGL2, MS4A6A, NLRP3, PLEK, RNASE6, SAMSN1, SPN, TMEM176B, ZEB2) related to prognosis were obtained through univariate Cox analysis and Lasso regression. C1QB, CD84, FGL2, MS4A6A, NLRP3, PLEK, SAMSN1, SPN, and ZEB2 were downregulated in NSCLC compared to non-cancer tissue. The mRNA of 13 genes were significantly expressed in pulmonary macrophages with strong cell specificity. Meanwhile, immunohistochemical staining showed that C1QB, CCL4, SPN, CD14, NLRP3, SAMSN1, MS4A6A, TMEM176B were expressed in different degrees in lung cancer tissues. ZEB2 (HR=1.4, P

For lung adenocarcinoma, arm aneuploidy landscape among primary and metastatic sites, and among different driver and frequently mutated gene groups have not been previously studied. We collected the largest cohort of LUAD patients (n=3533) to date and analyzed the profiles of chromosome arm aneuploidy (CAA), and its association with different metastatic sites and mutated gene groups. Our results showed distant metastasis (bone, brain, liver) were characterized by high CAA burden and biased towards arm losses compared to regional metastasis (pleura, chest) and primary tumors. Moreover, EGFR, MET, PIK3CA, PKHD1 and RB1 mutant groups were found to have high CAA burden, while those with BRAF, ERBB2 and KRAS mutations belonged to the low CAA burden group. Comparing EGFR L858R and EGFR 19del mutants, distinct CAA co-occurrences were observed. Network-based stratification with population based genomic evolution analysis revealed two distinct subtypes of LUAD with different CAA signatures and unique CAA order of acquisition. In summary, our study presented a comprehensive characterization of arm aneuploidy landscape and evolutionary trajectories in lung adenocarcinoma, which could provide basis for both biological and clinical investigations in the future.

Prosthetic joint infection (PJI) is a prevalent and severe complication characterized by high diagnostic challenges. Currently, a unified diagnostic standard incorporating both computed tomography (CT) images and numerical text data for PJI remains unestablished, owing to the substantial noise in CT images and the disparity in data volume between CT images and text data. This study introduces a diagnostic method, HGT, based on deep learning and multimodal techniques. It effectively merges features from CT scan images and patients’ numerical text data via a Unidirectional Selective Attention (USA) mechanism and a graph convolutional network (GCN)-based Feature Fusion network. We evaluated the proposed method on a custom-built multimodal PJI dataset, assessing its performance through ablation experiments and interpretability evaluations. Our method achieved an accuracy (ACC) of 91.4% and an area under the curve (AUC) of 95.9%, outperforming recent multimodal approaches by 2.9% in ACC and 2.2% in AUC, with a parameter count of only 68 M. Notably, the interpretability results highlighted our model’s strong focus and localization capabilities at lesion sites. This proposed method could provide clinicians with additional diagnostic tools to enhance accuracy and efficiency in clinical practice.

BackgroundThe aim of this study was to build and validate a radiomics nomogram by integrating the radiomics features extracted from the CT images and known clinical variables (TNM staging, etc.) to individually predict the overall survival (OS) of patients with non-small cell lung cancer (NSCLC).MethodsA total of 1,480 patients with clinical data and pretreatment CT images during January 2013 and May 2018 were enrolled in this study. We randomly assigned the patients into training (N = 1036) and validation cohorts (N = 444). We extracted 1,288 quantitative features from the CT images of each patient. The Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model was applied in feature selection and radiomics signature building. The radiomics nomogram used for the prognosis prediction was built by combining the radiomics signature and clinical variables that were derived from clinical data. Calibration ability and discrimination ability were analyzed in both training and validation cohorts.ResultsEleven radiomics features were selected by LASSO Cox regression derived from CT images, and the radiomics signature was built in the training cohort. The radiomics signature was significantly associated with NSCLC patients’ OS (HR = 3.913, p < 0.01). The radiomics nomogram combining the radiomics signature with six clinical variables (age, sex, chronic obstructive pulmonary disease, T stage, N stage, and M stage) had a better prognostic performance than the clinical nomogram both in the training cohort (C-index, 0.861, 95% CI: 0.843–0.879 vs. C-index, 0.851, 95% CI: 0.832–0.870; p < 0.001) and in the validation cohort (C-index, 0.868, 95% CI: 0.841–0.896 vs. C-index, 0.854, 95% CI: 0.824–0.884; p = 0.002). The calibration curves demonstrated optimal alignment between the prediction and actual observation.ConclusionThe established radiomics nomogram could act as a noninvasive prediction tool for individualized survival prognosis estimation in patients with NSCLC. The radiomics signature derived from CT images may help clinicians in decision-making and hold promise to be adopted in the patient care setting as well as the clinical trial setting.

The communication between macrophages and tendon cells plays a critical role in regulating the tendon-healing process. However, the potential mechanisms through which macrophages can control peritendinous fibrosis are unknown. Our data showed a strong pro-inflammatory phenotype of macrophages after a mouse tendon–bone injury. Moreover, by using a small-molecule compound library, we identified an aldehyde dehydrogenase inhibitor, disulfiram (DSF), which can significantly promote the transition of macrophage from M1 to M2 phenotype and decrease macrophage pro-inflammatory phenotype. Mechanistically, DSF targets gasdermin D (GSDMD) to attenuate macrophage cell pyroptosis, interleukin-1β, and high mobility group box 1 protein release. These pro-inflammatory cytokines and damage-associated molecular patterns are essential for regulating tenocyte and fibroblast proliferation, migration, and fibrotic activity. Deficiency or inhibition of GSDMD significantly suppressed peritendinous fibrosis formation around the injured tendon and was accompanied by increased regenerated bone and fibrocartilage compared with the wild-type littermates. Collectively, these findings reveal a novel pathway of GSDMD-dependent macrophage cell pyroptosis in remodeling fibrogenesis in tendon–bone injury. Thus, GSDMD may represent a potential therapeutic target in tendon–bone healing.

Mutation of the proto-oncogene K-Ras is one of the most common molecular mechanisms in non-small cell lung cancer. Many drugs for treating lung cancer have been developed, however, due to clinical observed K-Ras mutations, corresponding chemotherapy and targeted therapy for such mutation are not efficient enough. In this study, on the basis of the crystal structure of K-Ras, 21 analogues (TKR01–TKR21) containing urea or thiourea were rationally designed, which can effectively inhibit the lung cancer cell A549 growth. The designing of these compounds was based on the structure of K-Ras protein, and the related groups were replaced by bioisosteres to improve the affinity and selectivity. Biological testing revealed that compound TKR15 could significantly inhibit the proliferation of A549 cell with IC50 of 0.21 µM. Docking analysis showed that the TKR15 can effectively bind to the hydrophobic cavity and form a hydrogen bond with the Glu37. In addition, through flow apoptosis assay and immunofluorescence staining assay, it confirmed that this compound can inhibit A549 cell proliferation with the mechanism of blocking K-RasG12V protein and effector proteins interactions through the apoptotic pathway. In conclusion, our studies in finding novel potent compound (TKR15) with confirmed mechanism showed great potential for further optimisation and other medicinal chemistry relevant studies.

Abstract Thrombotic cardio‐cerebrovascular diseases seriously threaten human health. Currently, conventional thrombolytic treatments are challenged by the low utilization, inferior thrombus penetration, and high off‐target bleeding risks of most thrombolytic drugs, resulting in unsatisfactory treatment outcomes. Herein, it is proposed that these challenges can be overcome by precisely integrating the conventional thrombolytic strategy with photothermal therapy. After co‐assembly engineering optimization, a fibrin‐targeting peptide‐decorated nanoassembly of DiR (a photothermal probe) and ticagrelor (TGL, an antiplatelet drug) is prepared for thrombus‐homing delivery, abbreviated as FT‐DT NPs. The elaborately engineered nanoassembly shows multiple advantages, including simple preparation with high drug co‐loading capacity, synchronous delivery of two drugs with long systemic circulation, thrombus‐targeted accumulation with self‐indicating function, as well as photothermal‐potentiated thrombus penetration and thrombolysis with high therapeutic efficacy. As expected, FT‐DT NPs not only show bright fluorescence signals in the embolized vessels, but also perform photothermal/antiplatelet synergistic thrombolysis in vivo. This study offers a simple and versatile co‐delivery nanoplatform for imaging‐guided photothermal/antiplatelet dual‐modality thrombolysis.

BackgroundLung adenocarcinoma (LUAD) is a highly mortal cancer. Tertiary lymphoid structures (TLS) are ectopic lymphoid organs with similar morphological and molecular characters to secondary lymphoid organ. The aim of this study is to investigate the prognostic effect of a gene signature associated with TLSs, including B-cell-specific genes.MethodsClinical data of 515 LUAD patients in the TGCA cohort were used to examine the relationship of TLS signature with immune microenvironment, tumor mutational burden (TMB), and driver gene mutations. Patients were divided into the TLS signature high group and TLS signature low group, and comparative analysis of survival and its influencing factors between the two groups was performed. The resulting data were then validated in the GSE37745 cohort.ResultsTLS signature high group had significantly better overall survival (OS) and progression-free interval (PFI) as well as significantly higher infiltration of immune cell subsets, cancer immune cycle (CIC) signature except for immunogram score2 (IGS2), and expression of major checkpoint genes than the TLS signature low group. Notably, while TLS signature was not markedly associated with TMB and mutation frequencies of driver genes, there were significant differences in overall survival of patients with given mutation status of EGFR, KRAS, BRAF and TP53 genes between the TLS signature high and low groups.ConclusionThis study provided evidence that LUAD patients with high TLS signature had a favorable immune microenvironment and better prognosis, suggesting that TLS signature is an independent positive prognostic factor for LUAD patients.

In fringe projection profilometry, high-order harmonics information of distorted fringe will lead to errors in the phase estimation. In order to solve this problem, a point-wise phase estimation method based on a neural network (PWPE-NN) is proposed in this paper. The complex nonlinear mapping relationship between the gray values and the phase under non-sinusoidal distortion is constructed by using the simple neural network model. It establishes a novel implicit expression for phase solution without complicated measurement operations. Compared with the previous method of combining local image information, it can accurately calculate each phase value by point. The comparison results show that the traditional method is with periodic phase errors, while the proposed method can effectively eliminate phase errors caused by non-sinusoidal phase shifting.

Background: SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 2) is an important ATPase catalytic subunit in the switch-sucrose nonfermenting (SWI/SNF) complex. However, its relationship with the pathological features of NSCLC and its prognosis remain unclear. Methods: We retrospectively reviewed 2390 patients with surgically resected NSCLC, constructed tissue microarrays (TMAs) and performed immunohistochemical assays. We analyzed the correlation of SAMRCA2 with clinicopathological features and evaluated its prognostic value. Results: Among 2390 NSCLC cases, the negative expression ratios of SAMRCA2, SMARCA4, ARID1A, ARID1B and INI1 were 9.3%, 1.8%, 1.2%, 0.4% and 0%, respectively. In NSCLC, male sex, T3 and T4 stage, moderate and poor differentiation, tumor ≥ 2 cm, Ki67 ≥ 15%, SOX-2 negative expression, middle lobe lesion and adenocarcinoma were relative risk factors affecting SMARCA2-negative expression. In lung adenocarcinomas, high-grade nuclei, histological morphology of acinar and papillary, solid and micropapillary and TTF-1-negative expression were relative risk factors affecting SMARCA2-negative expression. Kaplan–Meier survival analysis showed that the OS was shorter in the SMARCA2-negative group. Multivariate survival analysis revealed that SMARCA2-negative expression was an independent factor correlated with a poor prognosis in NSCLC. Conclusion: In conclusion, SMARCA2-negative expression is an independent predictor of a poor outcome of NSCLC and is a potential target for NSCLC treatment.

Objective • The NLRP3 inflammasome plays a dual role in the occurrence and development of tumors, and its role in lung cancer remains unclear. This study aims to investigate the impact of NLRP3 inflammasome activation on the proliferation and migration of lung cancer cells. Methods • Data from the GEPIA, TCGA, and HPA databases were utilized to analyze the expression of NLRP3 in lung adenocarcinoma and its microenvironment. GO/KEGG enrichment analysis and GSEA analysis were employed to annotate the functions of differentially expressed genes related to NLRP3. The impact of NLRP3 inflammasome activation on the proliferation and migration of lung cancer cells was further investigated by CCK-8 assay and scratch assay. The effects of blocking NLRP3 inflammasome activation with IL-1RA and IL-18BP on the proliferation and migration of lung cancer cells were further assessed. Survival analysis was conducted to analyze the impact of NLRP3 expression on the prognosis of patients with lung adenocarcinoma. Results • The expression of NLRP3 in lung cancer was lower than in normal tissues, with notably higher expression observed in macrophages compared to other cells. Patients with higher NLRP3 expression exhibit increased infiltration of M2 macrophages. Activation of the NLRP3 inflammasome using LPS+ATP promotes the proliferation and migration of A549 cells. Simultaneous use of IL-1RA and IL-18BP reverses the promoting effect of NLRP3 inflammasome activation on cell proliferation and migration. Survival analysis results indicate that patients with high NLRP3 expression have a poorer prognosis compared to those with low NLRP3 expression (Hazzard Ratio =1.44; 95% Confidence Interval: 1.21-1.71). Conclusions • The activation of the NLRP3 inflammasome promotes the proliferation and migration of A549 cells through secretion of IL-1β and IL-18, potentially influencing patient prognosis. Simultaneously blocking IL-1β and IL-18 can reverse the pro-proliferative and migration-promoting effects. [ABSTRACT FROM AUTHOR]