This study aimed to evaluate the effect of co-administration of midazolam and dexmedetomidine on hemodynamics and stress response in elderly patients with non-small cell lung cancer (NSCLC).

In this prospective, randomized controlled trial, 154 elderly NSCLC patients scheduled for lobectomy in our oncology department from January 2019 to December 2021 were recruited. Patients were randomized 1:1 to receive either dexmedetomidine (control group) or dexmedetomidine plus midazolam (study group) for anesthesia during lobectomy via the random number table method, with 77 patients in each group. Perioperative indicators, hemodynamics, and stress reactions of the patients were recorded and compared between the two groups to investigate the efficacy of the two different anesthetic protocols.

No significant differences were observed between the two groups in terms of operative time, anesthesia time, and intraoperative bleeding volume (p > 0.05). Preoperative pain, pain at anesthesia recovery, and pain levels 7 days postoperatively were also comparable between the two groups. In the study group, the awakening time was 15 ± 2 min significantly shorter compared to the control group (25 ± 3 min). Cooperation within the first hour was significantly faster by 8.5 ± 0.5 min compared to 6.0 ± 1.0 min in the control group (p < 0.05). The cost of materials used was significantly higher in the study group, with an average of 300 ± 25 USD, compared to 200 ± 20 USD in the control group (p < 0.05). Additionally, the two groups showed no significant difference in the need for experience and surveillance (p > 0.05). Significantly lower visual analog scale (VAS) scores were found one day after the surgery in patients given dexmedetomidine plus midazolam than those anesthetized administered with dexmedetomidine only, suggesting an enhanced pain mitigation effect after incorporating midazolam for anesthetic induction. Patients treated with dexmedetomidine plus midazolam presented with a more stable hemodynamic status than those treated with dexmedetomidine only, as evidenced by the significantly lower variability of mean arterial pressure (MAP), oxygen saturation (SpO2), and heart rate (HR). Co-administration of dexmedetomidine plus midazolam for lobectomy anesthesia resulted in significantly lower serum cortisol (Cor) and norepinephrine (NE) concentrations in patients at anesthesia recovery than dexmedetomidine alone. However, this difference was not observed one day postoperatively. There was no statistically significant difference in the incidence of adverse reactions between the two groups.

The combination of midazolam with dexmedetomidine anesthesia in lobectomy improves the intraoperative hemodynamic status of elderly patients with NSCLC and mitigates their stress response. However, further research is required to explore the underlying mechanisms.

The objective of the present study was to elucidate the mechanism by which glycyrrhizin enhances the antitumor activity of cisplatin in non-small cell lung cancer. Initially, A549 cells were treated with different concentrations of glycyrrhizin (0.25-8 mM) or cisplatin (10-160 µM) for 48 h to investigate the effect of glycyrrhizin combined with cisplatin on A549 cells in vitro. Subsequently, A549 cells were divided into control (untreated), CP (20 µM cisplatin), GL (2 mM glycyrrhizin) and CP + GL (20 µM cisplatin + 2 mM glycyrrhizin) groups to elucidate the underlying mechanism of glycyrrhizin. After 48 h incubation, the viability and colony-forming ability of the cells were assessed using MTT and colony formation assays. Apoptosis levels and cell cycle progression were analyzed using flow cytometry and western blotting was used to evaluate apoptosis- and cell cycle-related proteins. Additionally, comet assays and western blotting were used to evaluate DNA damage and relevant proteins. The results demonstrated both glycyrrhizin and cisplatin individually reduced A549 cell viability in a concentration-dependent manner. Cisplatin demonstrated a lower half-maximal inhibitory concentration (IC50) at higher glycyrrhizin concentrations, with an IC50 value of ~35 µM with 2 mM glycyrrhizin. Furthermore, the combined treatment of glycyrrhizin and cisplatin synergistically reduced cell colony-forming ability, induced apoptosis and arrested the cell cycle at the G2 phase, showing greater efficacy when compared with either treatment individually. In addition, western blotting analysis demonstrated that, in comparison with treatment with cisplatin or glycyrrhizin alone, the combined treatment markedly increased the protein expression levels of B-cell lymphoma 2-associated X protein, cleaved-caspase-3/caspase-3, γH2AX, phosphorylated-checkpoint kinase 1 and phosphorylated-p53/p53, while notably reducing the protein levels of B-cell lymphoma 2, cyclin D1, cyclin-dependent kinase 2 and cyclin-dependent kinase 4. The findings of the present study indicate that glycyrrhizin enhances the antitumor efficacy of cisplatin in non-small cell lung cancer cells by modulating DNA damage and apoptosis.

Objective: This study aims to comprehensively evaluated the efficacy and safety of bronchial arterial chemoembolization (BACE) in the treatment of advanced nonsmall cell lung cancer (NSCLC) through a meta-analysis of single-group rate, providing evidence-based guidance for clinical treatment. Materials and Methods: A systematic search was conducted in PubMed, the Cochrane Library, Embase, and Web of Science databases for relevant studies up to January 15, 2024. Inclusion criteria encompassed single-arm or multi-arm studies of nonrandomized controlled trials, observational studies, and single-arm studies in English language, focusing on NSCLC patients treated with BACE. Data extraction, quality assessment, and statistical analysis were performed following predefined protocols. Results: In total, 172 articles were initially retrieved, with 11 studies meeting the inclusion criteria. The included studies comprised 510 patients. Meta-analysis revealed significant heterogeneity among studies for median progression-free survival (PFS), median overall survival (OS), objective response rate, and disease control rate. The combined median PFS was 6.87 months (95% confidence interval [CI] 5.30-8.44), and the combined median OS was 13.68 months (95% CI 10.69-16.67). Subgroup analysis based on intervention measures demonstrated varying efficacy outcomes. Adverse reactions associated with BACE were generally mild, with no reports of grade 3 or higher adverse events. Conclusion: BACE emerges as a promising treatment modality for advanced NSCLC, exhibiting favorable efficacy and safety profiles.

Stereotactic body radiation therapy (SBRT) is a promising therapeutic approach for inoperable, small (≤3 cm) primary lung cancer. However, the efficacy and safety of risk-adapted SBRT for treating large (>3 cm) primary lung cancer remains inadequately characterized.

Patients with large (>3 cm) primary lung cancer, diagnosed either clinically or histologically, were recruited between November 1, 2010 and December 31, 2022. Risk-adapted SBRT was administered in fractions (median, 5) for a total dose of 60 Gy (range, 45-63 Gy). The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), local failure (LF), regional failure (RF), distant metastasis (DM), cancer-specific mortality (CSM), and toxicity. Differences in baseline characteristics were balanced via propensity score matching (PSM) with the logistic regression model, as well as 1:1 ratio matching and inverse probability of treatment weighting (IPTW). The Cox proportional hazards model was used for univariate and multivariate analyses aimed at identifying prognostic factors influencing OS and PFS.

The 126 enrolled patients included 61 cases (48.4 %) diagnosed clinically and 65 cases (51.6 %) diagnosed pathologically. Following PSM and IPTW, no differences were found between patients diagnosed clinically versus pathologically in OS, PFS, tumor failure, and CSM. Univariate and multivariate analyses identified a Charlson comorbidity index ≥5 as an adverse prognostic factor for OS and PFS. One patient (0.8 %) in the pathologically diagnosed group developed grade 5 pneumonitis 2 months after undergoing SBRT.

Risk-adapted SBRT may be an optimal treatment for appropriately selected patients with a large (>3 cm) primary lung cancer lacking histologic confirmation.

ALK fusions, such as the classic EML4-ALK, are known drivers of lung cancer and effective therapeutic targets. However, variant ALK fusions, including intergenic fusions like LOC388942-ALK (LA), have been detected in increasing numbers of patients, with their roles in tumorigenesis and ALK inhibitor resistance remaining unclear. Using CRISPR/Cas9, we generated the LA fusion in A549 and H441 cells, confirming elevated ALK expression via qRT-PCR and immunohistochemistry (IHC) staining. Functional analyses showed that LA significantly promoted tumor growth in vitro and in vivo while conferring increased resistance to alectinib. RNA-seq revealed upregulation of the FOS pathway in LA tumors, identifying FOS as a potential therapeutic target. Subsequently, we demonstrated that FOS disruption and inhibition sensitized LA tumors to treatment. RNA-seq profiling demonstrated that FOS depletion in LOC388942-ALK tumor significantly downregulated multiple oncogenic pathways related to cell cycle progression, DNA replication fidelity, and extracellular matrix remodeling, suggesting a pivotal role of FOS in maintaining tumor growth. These findings establish LOC388942-ALK as a novel oncogenic driver in lung cancer, highlighting its role in tumor growth and ALK inhibitor resistance. Targeting FOS may provide a promising therapeutic strategy for tumors harboring this intergenic fusion.

Lung cancer poses a significant global burden with rising morbidity and mortality. Coal tar pitch-induced lung cancer is an occupational disease where early detection is crucial but challenging due to unclear pathogenesis. We established a malignant transformation model using BEAS-2B cells treated with coal tar pitch extract (CTPE). Macro- and micro-observations showed CTPE-induced alterations, including changes in cell morphology, enhanced proliferation and migration abilities, upregulated EGFR expression, modified levels of CYP1A1 and GSTM1 metabolizing enzymes, and a transition towards a mesenchymal phenotype. These findings strongly suggest that the cells have undergone malignant transformation. Metabolomics analysis revealed changes in 1120 metabolites, with 31 co-expressed, mainly in energy and amino acid metabolism. Small extracellular vesicles (SEVs) concentrations and EGFR levels were significantly altered. Correlation analysis identified a relationship between these biomarkers, implying their potential significance as early events in the initiation and progression of lung cancer. These findings provide valuable insights and a rationale for lung cancer screening and mechanistic investigations, thereby contributing to a deeper understanding of the disease.

Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer, accounting for 45.3% of all cases and serving as a major cause of cancer-related mortality. Although cisplatin (DDP) is a cornerstone in LUAD therapy, its efficacy is often compromised by resistance, leading to therapeutic failure and poor patient outcomes. Lipid metabolism and associated proteins, such as perilipin 3 (PLIN3), have been increasingly implicated in cancer progression and chemoresistance. However, the precise mechanisms through which PLIN3 contributes to cisplatin (DDP) resistance in LUAD remain poorly understood.

To investigate the role of PLIN3 in DDP resistance, its expression in LUAD tissues and its correlation with patient prognosis were analyzed using bioinformatics databases and validated through clinical sample analysis. The effects of PLIN3 knockdown and overexpression on DDP resistance and Wnt3a/β-catenin signaling were assessed using quantitative real-time PCR (qPCR), western blotting, cytotoxicity assays, and colony formation assays. Bioinformatics screening identified FOS-like antigen 1 (FOSL1) as a transcription factor positively correlated with PLIN3, and its involvement in DDP resistance was further examined both in vitro and in vivo.

PLIN3 expression is significantly elevated in LUAD tissues and correlates with poor overall survival. In LUAD cells, PLIN3 overexpression enhanced DDP resistance by upregulating Wnt3a expression and promoting β-catenin nuclear translocation. Bioinformatics analysis identified FOSL1 as a key transcription factor regulating PLIN3 expression. Experimental validation confirmed that FOSL1 directly binds to the PLIN3 promoter, activating the Wnt3a/β-catenin pathway and promoting DDP resistance. Knockdown of PLIN3 or inhibition of Wnt3a signaling reversed the effects of FOSL1 overexpression on DDP resistance.

This study demonstrates that PLIN3 contributes to DDP resistance in LUAD by activating the Wnt3a/β-catenin signaling pathway, with FOSL1 acting as a critical upstream regulator. Targeting the FOSL1/PLIN3/Wnt/β-catenin axis may provide a promising therapeutic strategy for overcoming chemoresistance in LUAD.

Radiotherapy (RT) resistance in non-small cell lung cancer (NSCLC) is a significant contributor to tumor recurrence. NAT10, an enzyme that catalyzes ac4C RNA modification, has an unclear role in RT resistance. This study aimed to explore the function of NAT10 in RT resistance in NSCLC. RT-resistant NSCLC cell lines (PC9R and A549R) were established through repeated irradiation. The impact of NAT10 on cellular immunity was evaluated by measuring immune cell populations, cytotoxicity levels, and markers of cell dysfunction. Results demonstrated elevated levels of ac4C and NAT10 in RT-resistant cells. Knockdown of NAT10 suppressed cell proliferation and enhanced immune function in PC9R and A549R cells by upregulating TNF-α and IFN-γ while downregulating PD-1 and TIM-3. Mechanistically, RT resistance in NSCLC was mediated by NAT10-dependent ac4C modification of KPNB1. Furthermore, KPNB1 facilitated PD-L1 nuclear translocation, promoting immune escape in RT-resistant NSCLC cells. Overexpression of KPNB1 enhanced cell proliferation but impaired immune function in RT-resistant NSCLC cells. In conclusion, this study demonstrates that NAT10 upregulates KPNB1 expression through ac4C modification, thereby promoting RT resistance in NSCLC via PD-L1 nuclear translocation. These findings reveal a novel mechanism underlying RT resistance in NSCLC.

Anaplastic lymphoma kinase (ALK) oncogenic fusions are an infamously evolving target in ALK fusion-positive (ALK+) non-small cell lung cancer (NSCLC). RNA interference (RNAi) is a potential alternative to small-molecule ALK inhibitors but suffers from poor cellular delivery and low stability, restricting sustained on-target therapeutic efficacy. To attain non-invasive direct RNAi at target sites in the lungs, inhalable vehicles are demanded to shield unstable siRNA from degradation in alkaline pleural fluid and to shuttle siRNA in the acidic tumor microenvironment. Here, we chemically synthesize a universal polyethylene glycol-poly(β-amino esters)-histidine(PEG-PBAE-His, PPH) system that enables siRNA-directed ALK gene silencing in ALK+ NSCLC with controlled release. The rational design of PEGylated polycationic PPH integrates the non-ionic nature, inertness, stealth effect, and low immunogenicity of PEG coronae with dual positively-charged PBAE and His to encapsulate siRNA payloads through enhanced electrostatic complexations. The assembled polyplexes with low polydispersity are overall anionic in alkaline pleural fluid and reversed into cationic charges at acidic pH, facilitating cellular uptake and lysosomal pH-governed release. The PPH-directed delivery significantly improves siRNA stability and ALK sequence-specific knockdown in H3122 cells, with a transfection efficiency comparable to commercial polyethylenimine but with lower cytotoxicity. The ALK-centric RNAi therapy prohibits cancer clonogenicity, migration, and invasion and induces potent growth inhibition in ALK+ NSCLC xenografts through inhalation. The inhalable polyplexes represent a transformative delivery platform that combines pH-responsive targeting, enhanced stability, and low toxicity, addressing critical limitations of existing siRNA delivery systems.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Tumor treating fields (TTFields) combined with anti-PD immunotherapy offers a promising strategy to address this issue. Nevertheless, the mechanism of action (MOA) of TTFields therapy combined with anti-PD immunotherapy in NSCLC has not been thoroughly investigated. This study aims to elucidate the MOA of the combined therapy from the aspect of improving the tumor immune microenvironment (TIME).

Using a mouse model of NSCLC, we tested the efficacy of TTFields therapy with anti-PD-1 and anti-PD-L1 immunotherapy. By RNA-seq, the differential genes and signaling pathways between combination therapy and anti-PD therapy groups were studied. In-vitro experiments validated the effects of TTFields on tumor cells for CD4+ T cell and CD8+ T cell infiltration, as well as the expression of tumor immunogenic death related genes and chemokines.

Combining TTFields with anti-PD-1 reduced tumor weight and volume, respectively, compared to controls (p < 0.05). RNA-seq analysis revealed 1,745 differentially expressed genes (DEGs) in the combination therapy group versus controls, including upregulated immune pathways and immunogenic cell death (ICD) associated genes. Further study showed that the combination therapy resulted in increased T cell infiltration compared to anti-PD immunotherapy alone, and TTFields induced higher level expression of ATP, HMGB1, CCL2, CCL8, CXCL9, and CXCL10 and inflammatory cytokines than control group. These effects collectively contributed to the altered TIME, and finally potentiated the efficacy of anti-PD therapy.

TTFields enhance the effectiveness of anti-PD immunotherapy by improving CD4+ T cells and CD8+ T infiltration via inducing ICD to increase CCL2/8 and CXCL9/CXCL10 expression of tumor cells. This study provides theoretical basis and new insights for evaluating the effectiveness of TTFields combined with anti-PD therapy for NSCLC.

Fei Yanning Formula (FYN) is extensively applied in clinical lung cancer treatment. However, the specific active constituents and targets of its therapeutic effects remain unclear.

The study aims to explore the active constituents and mechanism of FYN in delaying osimertinib resistance by network pharmacology analysis and experimental verification.

We collected the chemical constituents of the FYN based on the TCMSP database and relevant literature sources. Osimertinib resistance-related targets were acquired from the GeneCards database. We systematically construct the PPI network and KEGG analysis to explore hub targets and key pathways. The main active components of FYN were identified by molecular docking. Subsequently, we conducted in vitro experiments to verify its effect on osimertinib-resistant cells in lung cancer.

The PPI network and KEGG pathways analysis revealed six key targets linked to PI3K-AKT signaling pathways (ERBB2, EGFR, MET, HSP90AA1, MCL1, and IGF1R). RT-qPCR and immunohistochemical analyses demonstrated that FYN could suppress the expression of ERBB2, MET and HSP90AA1. Molecular docking indicated that Ethyl caffeate, the primary component in FYN, had a stronger binding ability with MET. Experiments illustrated that Ethyl caffeate inhibited the migration and proliferation of osimertinib-resistant cells, promoted apoptosis, and suppressed the expression level of MET.

FYN might delay osimertinib resistance by downregulating the expression of MET, which can be attributed to its active ingredient, Ethyl caffeate.

Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have become first-line therapies for advanced non-small cell lung cancer (NSCLC) with ALK rearrangements. This study investigates ALK-TKI-associated adverse events (AEs), focusing on identifying hepatotoxicity signals and previously undocumented safety concerns. Using disproportionality analysis of 56,864 reports from the FDA Adverse Event Reporting System (FAERS) database, we systematically classified AEs via the Medical Dictionary for Regulatory Activities (MedDRA). At the System Organ Class (SOC) level, crizotinib exhibited a significantly stronger signal for eye disorders, ceritinib was uniquely linked to gastrointestinal disorders, and loratinib was predominantly associated with metabolism and nutrition disorders. Several AEs previously undocumented in drug labels were identified, including pericardial effusion, elevated C-reactive protein, hemolytic anemia, hemoptysis, and decreased hemoglobin. Furthermore, crizotinib, ceritinib, and alectinib were significantly associated with hepatotoxicity, marked by elevated alanine aminotransferase, aspartate aminotransferase, and hepatic enzyme levels. These findings highlight the need for vigilant monitoring of unlabeled AEs and potential label updates, particularly for hepatotoxicity risks associated with crizotinib, ceritinib, and alectinib.

The response rate of immune checkpoint blockade (ICB) therapy for non-small-cell lung cancer (NSCLC) remains limited. Recent evidence suggests that obese cancer patients are more likely to benefit from ICB therapy, however, the specific mechanism needs further research. In this study, we found that anti-PD-1 therapy was more effective in obese NSCLC patients compared to normal weight patients and this was verified in mouse NSCLC model. Further bioinformatics analysis indicated that the glycolytic metabolism was markedly elevated in obese NSCLC patients. In vitro co-culture experiment showed that both increased glycolysis of tumor cells and external addition of lactate promoted T cell PD-1 expression. And, PD-1 upregulation was related to monocarboxylate transporter 1 (MCT1)-mediated lactate transport and subsequent lysine lactylation of histones in T cells. Based on the aforementioned data, our study contributes to better application of anti-PD-1 therapy in NSCLC.

To explore the application effect of Psychological Intervention based on the emotional adaptation theory combined with Feedback-based Health Education (PICFHE) on lung cancer patients.

A total of 216 lung cancer patients were divided into a control group and an observation group using a random number table method. The control group received routine nursing intervention, while the observation group received PICFHE on the basis of the control group. Psychological status was compared using the Self Rating Anxiety Scale (SAS) and Self Rating Depression Scale (SDS). Quality of life was measured using WHOQOL-BREF scale and the respiratory condition, satisfaction with the nursing staff, and incidence of adverse reactions were observed. Data were analyzed quantitatively using the software SPSS 20.0.

After intervention, scores of SAS and SDS, respiratory rate, and total incidence of adverse reactions in the observation group were significantly lower than those in the control group. After intervention, the level of maximum volume ventilation and the scores in all dimensions of the WHOQOL-BREF scale of the observation group were higher than those of the control group.

PICFHE can improve patients' psychological status, their quality of life and satisfaction with the nursing staff, and reduce the incidence of adverse reactions.

Cisplatin (DDP) is a commonly utilized chemotherapeutic agent. Nevertheless, the development of resistance to DDP significantly diminishes the effectiveness of DDP-based chemotherapy in patients with non-small cell lung cancer (NSCLC). In this study, we investigated the impact of endothelin 1 (EDN1) on the resistance to DDP in NSCLC.

The proliferation, invasion, and migration of NSCLC cells were detected by cell counting kit-8 and Transwell migration and invasion assays. ELISA was performed to analyze the inflammatory cytokines concentrations. The related protein levels of tumor necrosis factor (TNF) signaling pathway were analyzed by Western blot. Besides, a xenograft tumor mice model was established to explore the role of EDN1 in vivo.

The results showed that DDP-resistance upregulated EDN1 expression, cell viability, invasion, migration, and inflammation in NSCLC cells, while the results were reversed after EDN1 inhibition. EDN1 affected DDP-resistance of NSCLC by regulating TNF signaling pathway. Overexpression of TNF receptor-1 (TNFR1) reversed the decreased cell viability, invasion, migration, and inflammation induced by silencing EDN1 in A549/DDP cells. Moreover, silencing EDN1 inhibited tumor growth and the protein levels of EDN1 and TNFR1.

EDN1 promoted DDP resistance in NSCLC cells through the modulation of the TNF signaling pathway, suggesting a potential therapeutic intervention strategy for NSCLC.

Lung cancer is one of the most prevalent malignancies globally and is the leading cause of cancer-related mortality. Although cisplatin is a widely utilized chemotherapeutic agent, its clinical efficacy is often hampered by significant toxicity and undesirable side effects. Rosa canina, a medicinal plant, has demonstrated a range of beneficial biological activities, including anti-inflammatory, anticancer, immunomodulatory, antioxidant, and genoprotective effects.

This study aimed to investigate the potential of Rosa canina to enhance the anticancer efficacy of cisplatin in a dimethyl benz(a)anthracene-induced lung cancer model using female rats. The animals were administered Rosa canina, cisplatin, or a combination of both treatments. The expression levels of critical signaling molecules were evaluated, including phosphoinositide-3-kinase (PI3K), Akt, mammalian target of rapamycin (mTOR), cleaved poly (ADP-ribose) polymerase (PARP-1), myeloid differentiation factor 88 (MyD88), and tumor necrosis factor receptor-associated factor (TRAF), in addition to various autophagic markers. Furthermore, we assessed the levels of toll-like receptor 2 (TLR2), nuclear factor kappa B (NF-κB), and apoptotic markers in lung tissue, complemented by histopathological examinations.

The combined treatment of Rosa canina extract and cisplatin significantly inhibited lung cancer cell proliferation by downregulating PARP-1 and the TLR2/MyD88/TRAF6/NF-κB signaling pathway, as well as the PI3K/Akt/mTOR pathway. Moreover, this combination therapy promoted autophagy and apoptosis, evidenced by elevated levels of autophagic and apoptotic markers.

Overall, the findings of this study suggest that Rosa canina enhances the anticancer effects of cisplatin by inhibiting cancer cell proliferation while simultaneously inducing autophagy and apoptosis. Thus, Rosa can be used as adjuvant to cisplatin chemotherapy to overcome its limitations which may be considered a new approach during lung cancer treatment strategy.

Perioperative inflammatory indices reflect systemic inflammatory responses and have been linked to cancer progression and prognosis. This study aims to explore the differences in perioperative inflammatory indices between lung squamous cell carcinoma (LSCC) and adenocarcinoma (LUAD) and their association with long-term outcomes.

This study included 287 lung cancer patients who underwent curative resection between June 2016 and December 2017, comprising 61 cases of LSCC and 226 cases of LUAD. Perioperative baseline information and inflammatory cell counts were collected. Patients were followed up for a median duration of 76 months, during which disease-free survival (DFS) and overall survival (OS) were recorded. Cox regression analysis was used to evaluate the prognostic significance of inflammatory factor levels.

Significant differences were observed in white blood cell count and systemic inflammation response index (SIRI) between LSCC and LUAD (P < 0.05). Regression analysis identified age (OR=2.096, P=0.004), postoperative day 1 D-dimer level (OR=1.550, P<0.001), and Platelet-to-lymphocyte ratio (PLR) (OR=1.901, P=0.031) as independent risk factors for perioperative venous thromboembolism (VTE). Furthermore, open surgical approach (HR=2.437, P=0.016), tumor type (LSCC; HR=2.437, P=0.016), and PLR (HR=1.534, P=0.019) were independent risk factors for DFS.

Inflammatory index is key predictors of perioperative VTE and DFS in lung cancer, emphasizing their critical role in prognosis.

This meta-analysis aims to evaluate the association between pretreatment systemic immune-inflammation index (SII) levels and progression-free survival (PFS) and overall survival (OS) in NSCLC patients receiving immune checkpoint inhibitors (ICIs).

A systematic search was conducted across PubMed, Embase, and Web of Science. Hazard ratios (HRs) with 95 % confidence intervals (CIs) for PFS and OS were extracted or calculated. Random-effects models were employed to pool the results and subgroup analyses were performed based on study characteristics, treatment regimens, and analytical methods.

Two prospective and 11 retrospective studies involving 2342 NSCLC patients treated with ICIs were included. A high pretreatment SII was significantly associated with poor PFS (HR: 2.05, 95 % CI: 1.59-2.64, p < 0.001; I2 = 42 %) and poor OS (HR: 1.54, 95 % CI: 1.29-1.82, p < 0.001; I2 = 22 %). Subgroup analyses according to the country of the study, lines of treatment, cancer stage, methods for determining the cutoffs of SII, and the analytic models showed consistent results (p for subgroup difference all > 0.05). Interestingly, the subgroup analyses indicated a stronger association in patients receiving ICIs alone versus those receiving concurrent chemotherapy (p for subgroup difference = 0.04).

High pretreatment SII is associated with worse PFS and OS in NSCLC patients treated with ICIs, particularly for the patients receiving ICIs alone without concurrent chemotherapy.

Lung cancer has a higher incidence and mortality rate than other cancers, especially non-small cell lung cancer (NSCLC), accounting for 85% of the cases. The role of the circDENND4C/miR-200b/matrix metalloproteinase-9 (MMP-9) regulatory axis in NSCLC remains largely unknown.

NSCLC cell lines were used to examine the expression of circDENND4C, miR-200b, and MMP-9 via qRT-PCR or Western blot. The target relationship of circDENND4C, miR-200b, and MMP-9 was examined by RNA fluorescence in situ hybridization (RNA-FISH), immunofluorescence (IF), dual-luciferase reporter system, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. Then, a cell count kit-8 (CCK-8) experiment, flow cytometry, and migration/invasion assays were performed to assess the biological function of circDENND4C, miR-200b, and MMP-9 by transfecting with their overexpression or knockout plasmids in A549 cells. Finally, the proteins related to cell adhesion and tight junction were further tested by Western blot and IF.

circDENND4C and MMP-9 were found to be highly expressed in NSCLC cell lines, while miR-200b was lowly expressed in NSCLC cell lines. Moreover, circDENND4C could sponge miR-200b to target MMP-9. Subsequently, it was observed that knockdown of circDENND4C and MMP-9 or the upregulation of miR-200b repressed cell proliferation and cell cycle progression, increased cell apoptosis, and hindered cell migration and invasion. Finally, it was also found that the circDENND4C/miR-200b/MMP-9 regulatory axis might be involved with cell adhesion and tight junction to influence tumor metastasis.

Altogether, our study reveals a novel regulatory loop in which the circDENND4C/miR-200b/MMP-9 axis may modulate NSCLC progression, indicating potential biomarkers for the diagnosis or treatment of NSCLC.

To develop an accurate predictive model for identifying patients at high risk of pulmonary infection during radiochemotherapy.

We retrospectively analyzed data from 544 lung cancer patients treated at Hubei Cancer Hospital between May 2019 and October 2022. The patients were divided into training and validation groups (7:3 ratio). An external validation cohort of 100 patients treated from November 2022 to January 2024 was also included. Feature selection and model development were performed using machine learning algorithms, including Lasso regression, Random Forest, XGBoost, and Support Vector Machine (SVM). Model performance was evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, and decision curve analysis.

Key predictive factors for pulmonary infection risk were identified, including diabetes, chronic obstructive pulmonary disease, chemotherapy intensity, chemotherapy cycles, antibiotic use, age, Karnofsky Performance Status score, systemic inflammation index, prognostic nutritional index, and C-reactive protein. A nomogram-based prediction model was constructed, achieving ROC curve Area Under the Curve values of 0.889 in the training set, 0.897 in the validation set, and 0.875 in the external validation set, demonstrating strong classification ability and stability.

We developed a robust nomogram-based model incorporating eight key factors to predict the risk of pulmonary infection in lung cancer patients undergoing radiochemotherapy. This model can assist clinicians in early identification of high-risk patients, enabling timely interventions to improve patient outcomes and quality of life.

To evaluate the efficacy of concurrent chemoradiotherapy (CCRT) combined with immunotherapy (IT) for locally advanced non-small-cell lung cancer (LA-NSCLC). Short-term treatment outcomes during the two-year follow-up were recorded, and 2-year survival data were collected to analyze prognosis and identify factors affecting short-term outcome. Additionally, a predictive model was developed.

We conducted a retrospective analysis of 90 LA-NSCLC patients admitted between February 2018 and February 2020. Patients were grouped according to their treatment regimens: 45 patients treated with 4-6 cycles of CCRT followed by 1 year of Sintilimab therapy were assigned to the observation group, and 45 patients treated with cisplatin/carboplatin + albumin-bound paclitaxel for 4-6 cycles after CCRT were assigned to the control group. Short-term adverse reactions were recorded for both groups. Patients were followed up after 4-6 cycles of IT or chemotherapy, and short-term efficacy and toxicity were evaluated. During the 2-year follow-up, overall survival (OS) and progression-free survival (PFS) were recorded, and survival curves were plotted. The Cox proportional hazards model was used to identify factors influencing PFS in the observation group, and a predictive model was developed. The predictive value of relevant indicators for prognosis was assessed using receiver operating characteristic (ROC) curves.

The observation group showed superior short-term efficacy, with higher objective response rates (ORR) and disease control rates (DCR) compared to the control group (both P < 0.05). Regarding toxicity, the control group exhibited more severe adverse effects, particularly grade III and higher gastrointestinal reactions, leukopenia, thrombocytopenia, and anemia (all P < 0.05). The PFS was significantly higher in the observation group than that of the control group (P < 0.05). Additionally, the incidence of pneumonia was higher in the observation group, but it demonstrated better 2-year OS (P < 0.05). Cox multivariate analysis revealed that factors influencing PFS in the observation group included distant metastasis, tumor differentiation, platelet-to-lymphocyte ratio (PLR), and prealbumin (PAB). ROC analysis showed that the areas under the curve (AUC) for predicting prognosis based on PLR and PAB were 0.662 and 0.774, respectively, and the combined AUC of these indicators was 0.812.

CCRT combined with IT is an effective treatment for LA-NSCLC, improving survival outcomes. The predictive model developed may help assess prognosis and guide early clinical intervention. Attention should be given to pneumonia prevention and management during IT. Moreover, the combination of PLR and PAB enhances prognostic prediction for NSCLC patients undergoing CCRT plus IT.

Lung cancer, characterized by its high morbidity and mortality rates, has the capability to metastasize to various organs, thereby amplifying its detrimental impact and fatality. The metastasis of lung cancer is a complex biological phenomenon involving numerous physiological transformations. Exosomes, small membranous vesicles enriched with biologically active components, are pivotal in mediating intercellular communication and regulating physiological functions due to their specificity and stability. Extensive research has elucidated the production and functions of exosomes in cancer contexts. Multitude of evidence demonstrates a strong association between lung cancer metastasis and exosomes. Additionally, the concept of the pre-metastatic niche is crucial in the metastatic process facilitated by exosomes. This review emphasizes the role of exosomes in mediating lung cancer metastasis and their impact on the disease's development and the progression to other tissues. Furthermore, it explores the potential of exosomes as biomarkers for lung cancer metastasis, offering significant insights for future clinical advancements.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated remarkable efficacy in treating non-small cell lung cancer (NSCLC), but acquired resistance greatly reduces efficacy and poses a significant challenge to patients. While numerous studies have investigated the mechanisms underlying EGFR-TKI resistance, its complexity and diversity make the existing understanding still incomplete. Traditional approaches frequently struggle to adequately reveal the process of drug resistance development through mean value analysis at the overall cellular level. In recent years, the rapid development of single-cell RNA sequencing technology has introduced a transformative method for analyzing gene expression changes within tumor cells at a single-cell resolution. It not only deepens our understanding of the tumor microenvironment and cellular heterogeneity associated with EGFR-TKI resistance but also identifies potential biomarkers of resistance. In this review, we highlight the critical role of single-cell RNA sequencing in lung cancer research, with a particular focus on its application to exploring the mechanisms of EGFR-TKI-acquired resistance in NSCLC. We emphasize its potential for elucidating the complexity of drug resistance mechanism and its promise in informing more precise and personalized treatment strategies. Ultimately, this approach aims to advance NSCLC treatment toward a new era of precision medicine.

A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) plays critical roles in various cancer-associated biological events, such as cell multiplication, migration, and metastasis. This study employs both the TCGA database and patient samples to demonstrate that ADAM10 is highly expressed in non-small cell lung cancer (NSCLC) compared with normal tissue at different stages. Increased ADAM10 expression is positively correlated with decreased overall and recurrence-free survival. On the functional front, overexpression of ADAM10 promotes lung cancer cell progression, migration, and invasion, whereas downregulation of ADAM10 inhibits these processes. Mechanically, ADAM10 modulates the expression of Notch1, MMP9 and EMT markers such as Vimentin, N-cadherin, and E-cadherin. Overall, our findings suggest that ADAM10 may be a promising therapeutic and prognostic marker for NSCLC, emphasizing the importance of regulating its expression.

The abnormal expression and overactivation of the epidermal growth factor receptor (EGFR), a typical cancer marker for non-small cell lung cancer (NSCLC), are closely related to the tumorigenesis and progression of NSCLC. However, the endocytosis mechanism of EGFR in lung cancer is not yet known. Epsin3 (EPN3), a member of the endocytic adaptor protein family, is essential for the endocytosis of multiple receptors. In this study, we aimed to investigate the role of EPN3 in modulating EGFR function, its effects on NSCLC progression, and its potential involvement in tyrosine kinase inhibitor (TKI) resistance, which remains a significant hurdle in NSCLC treatment.

Our findings revealed that the expression of EPN3 is significantly up-regulated in NSCLC patients. Elevated EPN3 expression was proportional to shorter overall survival in patients with NSCLC. Functional analyses revealed that EPN3 directly interacts with EGFR, enhancing its recycling to the plasma membrane and preventing its degradation via the lysosomal pathway. This stabilization of EGFR led to sustained downstream signalling, promoting NSCLC cell proliferation and migration. Notably, mutations in the EGFR tyrosine kinase domain, which typically confer resistance to TKIs, did not alter the regulatory effect of EPN3.

EPN3 enhances EGFR signalling by promoting its recycling and stability, contributing to NSCLC progression and TKI resistance. Targeting EPN3 could offer a novel therapeutic strategy to overcome drug resistance in EGFR-driven NSCLC.

For patients with advanced non-small cell lung cancer (NSCLC) that have epidermal growth factor receptor (EGFR) mutations, EGFR tyrosine kinase inhibitors (TKIs) are the standard treatment and have significant clinical benefits. Third-generation TKIs, such as osimertinib, almonertinib and furmonertinib, are effective for the treatment of NSCLC that is EGFR-sensitizing mutation-positive and T790M-positive. Despite the efficacy of third-generation TKIs, patients inevitably develop resistance and the resistance mechanisms are heterogeneous. Second-generation inhibitors, such as afatinib, may be crucial in treating diseases that have developed resistance to first- or third-generation inhibitors. However, the clinical effect of afatinib in patients with acquired multiple EGFR mutations is not well defined. To the best of our knowledge, the present report describes the first case of a patient with lung adenocarcinoma who had multiple co-existing EGFR resistance mutations, including EGFR L718Q, EGFR C797S, EGFR C797G, EGFR L792H, EGFR V802F and EGFR V689L. These mutations conferred resistance to almonertinib, whilst maintaining sensitivity to afatinib.

Cancer remains a major cause of mortality and a significant economic burden in China. Exploring the disparities in cancer patterns and control strategies between China and developed countries may offer valuable insights for policy formulation and enhance cancer management efforts. This study examined the incidence, mortality, and disability-adjusted life year (DALY) burden of cancer in China, and compared these metrics with those observed in the United States (US) and the United Kingdom (UK).

Data on cancer incidence, mortality, and DALYs for China, the US, and the UK were sourced from the GLOBOCAN 2022 online database and the Global Burden of Disease 2021 study (GBD 2021). We utilized Joinpoint regression models to analyze trends in cancer incidence and mortality across these countries, calculating annual percent changes (APCs) and determining the optimal joinpoints.

In 2022, China recorded around 4,824,703 new cancer cases and 2,574,176 cancer-related deaths, contributing to 71,037,170 DALYs. China exhibited a lower cancer incidence rate compared to the US and the UK. Although cancer-related mortality in China is slightly lower than that in the UK, it is significantly higher than that in the US. Additionally, China experienced significantly higher DALY rates compared to both the US and UK. The cancer landscape in China was also undergoing significant changes, with a rapid rise in the incidence and burden of lung, colorectal, breast, cervical, and prostate cancers. Meanwhile, the incidence and burden of stomach cancer continued to decline. Although the incidence of liver and esophageal cancers was decreasing, the burden of liver cancer was increasing, while the burden of esophageal cancer remained largely unchanged.

The cancer profile of China is shifting from that of a developing country to one more typical of a developed country. The ongoing population aging and the rise in unhealthy lifestyles are expected to further escalate the cancer burden in China. Consequently, it is crucial for Chinese authorities to revise the national cancer control program, drawing on successful strategies from developed countries, while also accounting for the regional diversity in cancer types across China.

Recurrence and metastasis remain significant challenges in lung adenocarcinoma (LUAD) after radical resection. The mechanisms behind the recurrence and metastasis of LUAD remain elusive, and deregulated cellular metabolism is suspected to play a significant role. This study explores the metabolic and epigenetic regulation mediated by nicotinamide N-methyl transferase (NNMT) in LUAD.

Untargeted metabolomic analyses were performed to detect metabolism irregularities. Single-cell RNA sequencing (RNA-seq) databases and multiplex immunofluorescence analysis were used to identify the location of NNMT within the tumor microenvironment. The biological functions of NNMT were investigated both in vitro and in vivo, with RNA-seq and chromatin immunoprecipitation-PCR providing insights into underlying mechanisms. Finally, single-cell RNA-seq data and immunohistochemistry of primary tumors were analyzed to validate the main findings.

Untargeted metabolomic analyses revealed metabolic aberrations in amino acids, organic acids, lipids, and nicotinamide pathways, which are linked to metastasis of non-small cell lung cancer. NNMT is a key enzyme in nicotinamide metabolism, and we found the bulk tissue mRNA level of NNMT gene was inversely associated with LUAD metastasis. NNMT was proved to be predominantly expressed in cancer-associated fibroblasts (CAFs) within the stromal regions of LUAD, and a low stromal NNMT expression was identified as a predictor of poor disease-free survival following radical resection of LUAD. The isolation and primary culture of CAFs from LUAD enabled in vitro and in vivo experiments, which confirmed that NNMT negatively regulated the metastasis-promoting properties of CAFs in LUAD. Mechanistically, the downregulation of NNMT led to an increase in intracellular methyl groups by reducing the activity of the methionine cycle, resulting in heightened methylation at H3K4me3. This alteration triggered the upregulation of genes involved in extracellular matrix remodeling in CAFs, including those encoding collagens, integrins, laminins, and matrix metalloproteinases, thereby facilitating cancer cell invasion and metastasis. Reanalysis of single-cell RNA-seq data and immunohistochemistry assays of primary LUAD tissues substantiated NNMT's negative regulation of these genes in CAFs.

This study provides novel insights into the metabolic and epigenetic regulatory functions of NNMT in CAFs, expanding the current understanding of LUAD metastasis regulation and suggesting potential avenues for future research and therapeutic development.

Epidermal Growth Factor Receptor (EGFR) is an important target for the early evaluation, treatment, and postoperative follow-up in non-small cell lung cancer (NSCLC). Current detection technologies suffer from extended detection time and high rate of false positive amplification. Therefore, the development of rapid, highly sensitive and specific detection methods is of great significance for improving the diagnosis and treatment of lung cancer. In this study, we proposed a fast and sensitive detection method termed Thermus thermophilus Argonaute (Ttago)-Coupled-Multiplex-digital-recombinase polymerase amplification (RPA)-Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a (TCMDC) detection method, integrating EGFR mutation template enrichment. Based on the cleavage principle of TtAgo, the wild type (WT) template was enriched under the action of double-guide DNA. Two CRISPR RNAs, not restricted by protospacer adjacent motif (PAM) sites, were introduced to target EGFR genes. By combining RPA with CRISPR-Cas12a, we established a single-pot, ultra-sensitive (1 copy, 0.1 %), and visually detectable method for EGFR detection. We further verified the feasibility of this approach using clinical serum samples from lung cancer patients, achieving rapid (within 1 h) and visual detection of EGFR, thereby presenting a promising clinical tool for the detection of lung cancer.

Perioperative treatment with toripalimab combined with chemotherapy was efficacious and safe in resectable stage II-IIIA non-small cell lung cancer (NSCLC); however, little is known about whether this treatment regimen could convert unresectable NSCLC to resectable.

This study enrolled 40 treatment-naive patients with initially unresectable stage IIIA-IIIB NSCLC. Toripalimab (240 mg) and platinum-doublet chemotherapy were administered every 3 weeks for 2-4 cycles. Surgical resection was decided after assessing the efficacy of induction therapy. The primary outcome was the R0 resection rate. The secondary outcomes included safety, overall survival, disease-free survival, event-free survival, objective response rate, major pathological response (MPR), and pathological complete response (pCR). Available baseline tumor biopsy samples were used for molecular biomarker analyses, including bulk RNA sequencing and multiplex immunostaining. This study was registered at ClinicalTrials.gov: NCT04144608.

Of the 40 patients who received induction toripalimab plus chemotherapy, 29 (72.5%) patients received surgery, and all achieved R0 resection (100% R0 rate). Of these patients, 17 (58.6%) achieved MPR, with 10 (34.5%) patients evaluated as pCR. With a median follow-up of 31.8 months (95% confidence interval [CI]: 24.2-39.4), the median event-free survival and overall survival were not reached. Molecular analyses revealed highly expressed gene sets for germinal center B cells (signatures of tertiary lymphoid structure [TLS]) at baseline among patients with pCR compared to patients with non-pCR, suggesting that the TLS status of the patients was associated with the induction of immunotherapy responses.

Toripalimab-based induction treatment of initially unresectable NSCLC yielded a high R0 rate and MPR rate, with a good safety profile and encouraging survival outcomes.

This work was funded by the National Natural Science Foundation of China.

To explore the impact of neoadjuvant immunotherapy on the clinical efficacy of stage IIIA-N2 non-small cell lung cancer (NSCLC) patients.

The retrospective study was conducted on 120 patients with stage IIIA-N2 NSCLC admitted to our hospital during April 2020 to April 2022. The control group received local chemotherapy, while the combination group received neoadjuvant immunotherapy on the basis of chemotherapy. The treatment efficacy, immune function, PD-1 and PD-L1 (SP142) expression levels, and changes in inflammatory factors were compared between the two groups. Kaplan Meier survival curve was used to analyze the overall survival rate.

Total effective rate in the control group was 53.33 % (15.00 % recovery + 16.66 % significant effect + 21.66 % effective), and the combined group had a higher total effective rate of 85.00 % (41.66 % recovery + 23.33 % significant effective + 20.00 % effective) (P < 0.001). After intervention, the combination group had largely increased immune indicators levels, including CD3+, CD4+ and CD4+/CD8+ (P < 0.001), but reduced levels of CD8+, PD-1 and PD-L1 (SP142) than the control group (P < 0.001). After intervention, the levels of inflammatory factors in the combination group were also reduced than the control group (P < 0.001). Compared to the control group with an adverse reaction rate of 31.66 % (8.33 % gastrointestinal reaction + 11.66 % hair loss + 6.66 % proteinuria + 5.00 % diarrhea), the combined group had much lower adverse reaction rate of 11.66 % (1.66 % gastrointestinal reaction + 5.00 % hair loss + 3.33 % proteinuria + 1.66 % diarrhea) (P < 0.05). After 24 months of follow-up, the overall survival rate was 58.33 % (35/60) and 40.00 % (24/60) in the combination group and the control group, respectively. The Kaplan Meier survival curve analysis showed a statistically significant difference in overall survival rate between the two groups (P < 0.05).

Neoadjuvant immunotherapy had a more significant therapeutic effect on stage IIIA-N2 NSCLC patients by reducing immunosuppressive and inflammatory factors, improving immune function, and reducing the occurrence of adverse reactions.

Programmed cell death 1/programmed death ligand-1 (PD-L1)-based immune checkpoint blockade is an effective treatment approach for non-small-cell lung cancer (NSCLC). However, immunohistochemistry does not accurately or dynamically reflect PD-L1 expression owing to its spatiotemporal heterogeneity. Herein, we assessed the feasibility of using a 68Ga-labeled anti-PD-L1 nanobody, 68Ga-NODAGA-NM-01, for PET imaging of PD-L1.

Micro-PET/CT and biodistribution studies were performed on PD-L1-positive and -negative tumor-bearing mice. Additionally, a preliminary clinical study was performed on two patients with NSCLC. NM-01 was radiolabeled with 68Ga without further purification under mild conditions.

68Ga-NODAGA-NM-01 exhibited radiochemical purity (> 98%), high stability in vitro, and rapid blood clearance in vivo. Specific accumulation of 68Ga-NODAGA-NM-01 was observed in PD-L1-positive tumor-bearing mice, with a good tumor-to-background ratio 0.5h post-injection. Furthermore, 68Ga-NODAGA-NM-01 PET/CT imaging was found to be safe with no adverse events and distinct uptake in primary and metastatic lesions of the PD-L1-positive patient, with a higher maximal standardized uptake value than that in lesions of the PD-L1-negative patient 1h post-injection.

68Ga-NODAGA-NM-01 can be prepared using a simple method under mild conditions and reflect PD-L1 expression in primary and metastatic lesions. However, our findings need to be confirmed in a large cohort.

NCT02978196. Registered February 15, 2018.

Lung cancer progression is characterized by intricate epigenetic changes that impact critical metabolic processes and cell death pathways. In this study, we investigate the role of histone lactylation at the AIM2 locus and its downstream effects on ferroptosis regulation and lung cancer progression. We utilized a combination of biochemical assays, including chromatin immunoprecipitation (ChIP), quantitative real-time PCR (qRT-PCR), and western blotting to assess histone lactylation levels and gene expression. To evaluate the functional consequences, we employed gain- and loss-of-function approaches using shikonin treatment and siRNA knockdowns in lung cancer cell lines. Additionally, we assessed the impact of these interventions on ferroptosis markers and lung cancer cell viability. Our results reveal that increased histone lactylation at the AIM2 locus correlates with enhanced transcriptional activity of AIM2, leading to reduced ferroptosis through modulation of ACSL4 and STAT5B. Furthermore, we demonstrate that shikonin, a natural naphthoquinone derivative, effectively downregulates PKM2 and AIM2 expression, thereby inhibiting lung cancer progression by counteracting the effects of histone lactylation on AIM2 expression. These findings highlight the importance of histone lactylation in regulating AIM2 expression and ferroptosis in lung cancer cells. They also suggest that targeting PKM2 and AIM2, particularly through the use of shikonin, could be a promising strategy for developing novel therapies against lung cancer.

Ferroptosis is not only a consequence of inflammation, but also a dynamic process. Recent bioinformatics analysis suggests that ferroptosis related genes might be associated with lung adenocarcinoma (LUAD). CPT1A and GDF15 are critical for the process of ferroptosis and development of inflammation; however, little study focused on the mutation level of these genes in patients with LUAD.

The candidate SNPs in CPT1A and GDF15 were genotyped in 320 pairs of LUAD patients and controls using Mass ARRAY platform. Moreover, the different expression of CPT1A and GDF15 in LUAD cases and healthy controls were validated by qRT-PCR and ELISA.

The rs80356779 G > A, rs3019594 C > T, rs888663 T > G and rs4808793 G > C all exhibited an increased risk of the disease (p < 0.05). Moreover, the rs80356779-GA, rs3019594-TT, rs888663-TG and rs4808793-CC genotypes were all related to different levels of increase in LUAD risk (p < 0.05). Genetic model results showed that rs80356779 G > A, rs888663 T > G and rs4808793 G > C were associated with LUAD susceptibility under dominant and additive models (p < 0.05), while rs3019594 C > T was correlated with an elevated risk of the disease in all three models (p < 0.05). Additionally, patients with rs80356779 G > A and rs3019594 C > T exhibited lower expression and serum concentration of CPT1A compared with wile types, and patients with rs888663 T > G and rs4808793 G > C exhibited higher serum and expression level of GDF15.

The results provided new clues for the role of ferroptosis in LUAD and new potential targets for screening of susceptible population.

This review highlights recent progress in exosome-based drug delivery for cancer therapy, covering exosome biogenesis, cargo selection mechanisms, and their application across multiple cancer types. As small extracellular vesicles, exosomes exhibit high biocompatibility and low immunogenicity, making them ideal drug delivery vehicles capable of efficiently targeting cancer cells, minimizing off-target damage and side effects. This review aims to explore the potential of exosomes in cancer therapy, with a focus on applications in chemotherapy, gene therapy, and immunomodulation. Additionally, challenges related to exosome production and standardization are analyzed, highlighting the importance of addressing these issues for their clinical application. In conclusion, exosome-based drug delivery systems offer promising potential for future cancer therapies. Further research should aim to enhance production efficiency and facilitate clinical translation, paving the way for innovative cancer treatment strategies.

Recently there has been an increasing number of studies have explored apoptosis mechanisms in lung cancer (LC). However, no researchers have conducted a bibliometric analysis of the most cited articles in this field.

To examine the top 100 most influential and cited publications on apoptosis in non-small cell lung cancer (NSCLC) from 2004 to 2023, summarizing research trends and key focus areas.

This study utilized the Web of Science Core Database (WOSCC) to research NSCLC apoptosis from 2004 to 2023, using keyword selection and manual screening for article searches. Bibliometrix package of R software 4.3.1 was used to generate distribution statistics for the top ten institutions, journals and authors. Citespace6.2. R6 was used to create the visualization maps for keyword co-occurrence and clustering. VOSviewer1.6.19 was used to conduct cluster analysis of publishing countries (regions), with data exported to SCImago Graphica for geographic visualization and cooperation analysis. VOSviewer1.6.19 was used to produced co-citation maps of institutions, journals, authors, and references.

From 2004 to 2023, 13316 articles were retrieved, and the top 100 most cited were chosen. These were authored by 934 individuals from 269 institutions across 18 countries and appeared in 45 journals. Citations ranged from 150 to 1,389, with a median of 209.5. The most influential articles appeared in 2005 and 2007 (n=13). The leading countries (regions), institutions, journals and authors were identified as the United States (n=60), Harvard University (n=64), CANCER RESEARCH (n=15), SUN M and YANG JS (n=6). The top five keywords were "expression", "activation", "apoptosis", "pathway" and "gefitinib". This study indicates that enhancing apoptosis through circular RNA regulation and targeting the Nrf2 signaling pathway could become a key research focus in recent years.

Apoptosis has been the subject of extensive research over many years, particularly in relation to its role in the pathogenesis, diagnosis, and treatment of NSCLC. This study aims to identify highly influential articles and forecast emerging research trends, thereby offering insights into novel therapeutic targets and strategies to overcome drug resistance. The findings are intended to serve as a valuable reference for scholars engaged in this field of study.

Forkhead box J2 (FOXJ2) induces cell apoptosis and restrains epithelial-mesenchymal transition in lung cancer, but its capability to serve as a prognostic biomarker in non-small cell lung cancer (NSCLC) remains unclear. Hence, this study intended to investigate the association of FOXJ2 with clinical characteristics, disease-free survival (DFS), and overall survival (OS) in NSCLC patients who received surgical resection. Totally, 182 NSCLC patients who received surgical resection were retrospectively enrolled. Their tumor FOXJ2 expression was quantified by immunohistochemistry (IHC). FOXJ2 IHC score = s taining intensity × density, with a total score of 12. FOXJ2 IHC score was 0 in 128 (70.3%) patients and > 0 in the remaining 54 (29.7%) patients; meanwhile, it was ≤ 3 in 157 (86.3%) patients and > 3 in 25 (13.7%) patients. FOXJ2 was negatively related to node (N) stage (P = 0.013) and tumor-nodes-metastasis (TNM) stage (P = 0.034). Intriguingly, FOXJ2 IHC score was reduced in patients with adjuvant chemotherapy than in patients without adjuvant chemotherapy (P = 0.036). The median DFS and OS (95% confidence interval) were 35.0 (31.3-38.7) months and 48.8 (43.7-53.9) months, respectively. Notably, FOXJ2 IHC score > 0 (P = 0.006) and > 3 (P = 0.002) was correlated with prolonged DFS. Also, FOXJ2 IHC score > 0 (P = 0.027) and > 3 (P = 0.028) was associated with longer OS. After adjustment by backward stepwise multivariate model, FOXJ2 IHC score > 3 was independently associated with prolonged DFS (hazard ratio = 0.367, P = 0.009). In conclusion, tumor FOXJ2 negatively links with N stage and TNM stage; moreover, FOXJ2 IHC score > 3 estimates prolonged DFS and OS in NSCLC patients who received surgical resection.

Metastasis of non-small cell lung cancer (NSCLC) is a leading cause of high mortality. In recent years, the role of M2 macrophages in promoting tumor metastasis within the tumor microenvironment has garnered increasing attention. This study aims to investigate the role and potential mechanisms of the ITGB4/GNB5 axis in regulating M2 macrophage reprogramming and influencing NSCLC metastasis.

This study first used single-cell sequencing technology to reveal the diverse subpopulation structure of NSCLC tumor tissues. Data analysis then identified the correlation between M2 macrophages and the malignant phenotype of NSCLC. Flow cytometry and immunohistochemistry were used to detect changes in M2 macrophages in NSCLC tissues. The impact of the ITGB4/GNB5 axis on M2 macrophage function was assessed through RNA sequencing and proteomic analysis. Finally, in vitro cell experiments and in vivo mouse models were used to validate the function and regulatory mechanisms of this axis.

Our study found diverse cellular subpopulations in NSCLC tumor tissues, with M2 macrophages closely associated with the malignant phenotype of NSCLC. We identified ITGB4 as a characteristic gene of NSCLC and predicted GNB5 as an interacting gene through database analysis. Activation of the ITGB4/GNB5 axis was shown to enhance M2 macrophage polarization, promoting their accumulation in the tumor microenvironment. This change further facilitated NSCLC invasion and metastasis by modulating related cytokines and signaling pathways. Animal experiments demonstrated that inhibition of the ITGB4/GNB5 axis significantly reduced tumor growth and metastasis.

The ITGB4/GNB5 axis reshapes the TME by promoting M2 macrophage polarization and functional enhancement, thereby facilitating tumor invasion and metastasis in NSCLC. This research provides new insights into the molecular mechanisms of NSCLC and offers potential molecular targets for future targeted therapies.

Non-small-cell lung cancer (NSCLC) represents a predominant histological subtype of lung cancer, characterized by high incidence and mortality rates. Despite significant advancements in therapeutic strategies and a deeper understanding of targeted therapies in recent years, tumor resistance remains an inevitable challenge, leading to poor prognostic outcomes. Several studies have indicated that sphingosine kinase 1 (SPHK1) plays a regulatory role in epidermal growth factor receptor (EGFR) signaling, and its elevated expression may be associated with resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Furthermore, the catalytic product of SPHK1, sphingosine 1-phosphate (S1P), along with its receptor, sphingosine 1-phosphate receptor 3 (S1PR3), plays a regulatory role in the function of the EGFR. However, the specific effects of the SPHK1/S1P/S1PR3 axis on EGFR in NSCLC, as well as the combined effects of SPHK1/S1P/S1PR3 inhibitors with the EGFR-TKI gefitinib, remain to be elucidated. In the present study, we investigated the correlation between SPHK1 expression levels and the survival rates of NSCLC patients, the relationship between SPHK1 or S1PR3 and EGFR, and the impact of SPHK1 expression on the half-maximal inhibitory concentration (IC50) of gefitinib in NSCLC. In A549 cells, the phosphorylation of EGFR was significantly reduced following SPHK1 knockdown. Utilizing SPHK1/S1P/S1PR3 inhibitors, namely PF543, TY52156, and FTY720, we established that the SPHK1/S1P/S1PR3 axis modulates EGFR activation in NSCLC. Furthermore, these signaling inhibitors enhanced the anti-proliferative efficacy of the EGFR-TKI gefitinib. RNA sequencing analysis revealed substantial alterations in 85 differentially expressed genes in NSCLC cells treated with the combination of FTY720 and gefitinib. These genes were predominantly associated with pathways such as axon guidance, microRNAs in cancer, and the JAK-STAT signaling pathway, among others. Overall, targeting the SPHK1/S1P/S1PR3 signaling pathway represents a promising therapeutic strategy to enhance gefitinib sensitivity in NSCLC.