Catalase (CAT) plays a crucial role in converting hydrogen peroxide (H₂O₂) into water and oxygen, which can help alleviate oxidative stress in body. However, whether CAT is associated with the prognosis and immunotherapy response in patients with non-small cell lung cancer (NSCLC) requires further investigation. This study collected data from over 3,170 NSCLC cases across multiple countries. Thirteen machine learning algorithms were employed to identify the most effective diagnostic model, with performance evaluated based on area under the curve (AUC) values. The prognostic significance of CAT expression was assessed in relation to survival, tumor recurrence, and tumor differentiation in NSCLC patients. Additionally, the effectiveness of immunotherapy in relation to CAT expression was evaluated using an immunotherapy dataset. The GDSC database was utilized to examine the correlation between CAT expression and sensitivity to potential therapeutic agents. A multi-omics approach was then applied to analyze the expression and distribution of CAT in NSCLC. In vitro experiments were conducted to validate CAT expression in lung cancer cell lines, and its impact on cell proliferation and migration was assessed using CCK-8 assays, scratch assays, and colony formation assays following transfection with a CAT overexpression construct. The regulatory role of CAT in oxidative stress was further evaluated by adding hydrogen peroxide. Finally, the xenograft tumor mouse model was established to observe the effect of CAT on macrophage phenotype. We first observed that CAT exhibited the highest AUC value in the machine learning model. Subsequent analyses revealed that NSCLC patients with high CAT expression had prolonged survival, reduced tumor recurrence, and reduced tumor poor differentiation, as confirmed by data from multiple global national databases. Moreover, these patients showed greater responsiveness to immunotherapy and experienced prolonged progression-free survival (PFS). The high CAT expression cohort also exhibited increased sensitivity to Cisplatin, Savolitinib, and Docetaxel. Additionally, we also verified the low expression of CAT in tumor tissues by RT-qPCR and immunohistochemistry. Furthermore, overexpression of CAT inhibited lung cancer cell proliferation and migration, while significantly enhancing its ability to regulate hydrogen peroxide levels. Notably, in the xenograft tumor mouse model, we observed that CAT may suppress tumor growth by alleviating tissue hypoxia and facilitating the polarization of tumor-associated macrophage from the M2 phenotype to M1. This study demonstrated the potential of CAT as a prognostic biomarker for NSCLC. Targeting CAT might provide an effective strategy for improving patient survival and the efficacy of immunotherapy.

Despite advancements in diagnostic techniques and therapeutic strategies, the prognosis for Lung adenocarcinoma (LUAD) patients remains poor. Cell proliferation and cycle dysregulation drive cancer via uncontrolled cell growth. These genes also modulate tumor immune microenvironment (TIME), yet the precise mechanisms in LUAD remain largely unknown. This study aimed to identify key proliferation-cycle genes in LUAD, characterize the TIME associated with proliferation-cycle gene signatures and assess the impact of proliferation-cycle gene signatures on immunotherapy responsiveness. We analyzed The Cancer Genome Atlas (TCGA) LUAD transcriptomic data and identified eight proliferation-cycle-related risk genes (seven up-regulated: FAP, IL2RA, ITGA2, CHORDC1, PIM2, POU3F2, CD180; one down-regulated: FKBP1B). Independent cross-validation using the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) dataset confirmed the consistent expression patterns for all eight candidate genes in LUAD tumors. A risk model based on these genes stratified patients into distinct prognostic groups, revealing: (1) Survival disparity: High-risk patients exhibited poorer overall survival (p = 6.2e−05). (2) Immunosuppressive TIME: Elevated risk scores correlated with enhanced immune infiltration (p = 2.9e−12), enriched immunosuppressive populations (Tregs), reduced cytotoxic effectors (CD8+ T cells), and up-regulated immune checkpoint molecules (PDCD1/PD-L1, CTLA4). (3) Scientific implications: Risk signatures exhibited no significant correlation with tumor mutational burden (TMB), yet uncovered novel candidate targets with therapeutic potential, meriting further mechanistic exploration. Proliferation-cycle gene signatures are robust biomarkers for LUAD risk stratification, prognosis, and immune landscape prediction. Their mechanistic integration into multi-dimensional oncological models could reveal previously unrecognized layers of antitumor immune regulation.

Cytokines link inflammation to tumorigenesis, but the role of post-translational modifications in regulating their function within the extra-tumoral environment remains poorly defined. Here, we identify tumor-derived tumor necrosis factor (TNF) receptor superfamily member 11B (TR11B) as a key driver of lung adenocarcinoma (LUAD) progression and therapeutic resistance. Mechanistically, O-GlcNAc transferase (OGT)-mediated O-GlcNAcylation at serine 151 stabilizes TR11B and facilitates its interaction with the membrane protein EPS15 homology domain-containing protein 1 (EHD1), promoting cyclin dependent kinase 2 (CDK2) phosphorylation and cell cycle progression. Clinically, elevated O-GlcNAcylated TR11B correlates with advanced LUAD. Genetic deletion of Ogt suppresses tumor development in LUAD mouse models. Importantly, celecoxib, an U.S. Food and Drug Administration (FDA)-approved drug, inhibits O-GlcNAcylation and exerts antitumor effects. These findings reveal a pathological role for cytokine O-GlcNAcylation in LUAD and identify this axis as a potential therapeutic target.

Serum-derived tumor-associated microRNAs (miRNAs) have emerged as clinically valuable biomarkers for early cancer detection and prognostic evaluation. The development of robust analytical platforms enabling ultrasensitive miRNA quantification remains an urgent priority in molecular diagnostics. Herein, a well-designed functional hairpin DNA template (H) combined with the CRISPR/Cas12a system was proposed as a novel strategy for ultrasensitive detection of lung cancer-associated miRNAs. The H-sequence undergoes a topological transition upon specific recognition of the target miRNA, initiating an isothermal exponential amplification reaction (iEXPAR) that continuously releases amplicons. These amplicons, in turn, activate the CRISPR/Cas12a system, resulting in signal amplification. This approach achieves a linear detection range from 20 fM to 2 nM, with an impressive detection limit as low as 26 fM. Due to the programmability of DNA sequences, this strategy holds great potential for the sensitive detection of a wide range of other nucleic acid targets.

Neuroendocrine tumor (NET) is a deadly malignancy disease that can be found anywhere in the body. The lack of tumor-specific treatment led to the worse prognosis of NET. Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs), such as alectinib and crizotinib, have been used in the treatment of NET patients with ALK rearrangement. However, the response to ensatinib in NET patients with rare ALK fusion has been rarely reported. Here, we report a 55-year-old Chinese female patient with NET (atypical carcinoid tumor) and a novel CEP44-ALK rearrangement identified by next-generation sequencing (NGS). NGS can provide more information on mutation landscape for rare neuroendocrine tumors to guide treatment and assist in clinical decisions by presenting molecular changes. The patient received ensartinib (225 mg/day) for 18 months until disease progression in June 2024 and achieved a radiographic partial response. Although patients with ALK fusions showed response to ensatinib in nonsmall cell lung cancer (NSCLC), this study first reports a metastatic NET case with a novel CEP44-ALK rearrangement that responded favorably to ensartinib.

BACKGROUND:Non-small cell lung cancer (NSCLC) is one of the predominant malignancies globally. Percutaneous thermal ablation (PTA) has gained widespread use among NSCLC patients, with the potential to elicit immune responses but limited therapeutic efficacies for advanced-stage disease. T-helper type 9 (Th9) cells are a subset of CD4+ effector T cells with robust and persistent anti-tumor effects. This study proposes to develop PTA-Th9 cell integrated therapy as a potential strategy for NSCLC treatment.METHODS:The therapeutic efficacies were measured in mice models with subcutaneously transplanted, recurrence, or lung metastatic tumors. The tumor microenvironments (TMEs) were evaluated by flow cytometry. The cytokine levels were assessed by ELISA. The signaling molecules were determined by quantitative PCR and Western blotting. The translational potential was tested in the humanized NSCLC patient-derived xenograft (PDX) model.RESULTS:We find that PTA combined with adoptive Th9 cell transfer therapy substantially suppresses tumor growth, recurrence, and lung metastasis, ultimately extending the survival of mice with NSCLC grafts, outperforming both PTA and Th9 cell transfer monotherapy. Analysis of TMEs indicates that combinatorial therapy significantly augments tumor-infiltrating Th9 cells, boosts anti-tumor effects of CD8+ T cells, and remodels tumor immunosuppressive microenvironments. Moreover, combinatorial therapy significantly strengthens the regional and circulation immune response of CD8+ T cells in mice with tumor lung metastasis and induces peripheral CD8+ T effector memory cells in mice with tumor recurrence. Mechanically, PTA reinforces the anti-tumor ability of Th9 cells primarily through upregulating interleukin (IL)-1β and subsequently activating the downstream STAT1/IRF1 pathway, which could be effectively blocked by intercepting IL-1β signaling. Finally, the enhanced therapeutic effect of combinatorial therapy is validated in humanized NSCLC PDX models.CONCLUSIONS:Collectively, this study demonstrates that combinatorial therapy displays robust and durable anti-tumor efficacy and excellent translational potential, offering excellent prospects for translation and emerging as a promising approach for NSCLC treatment.

Background Mitochondrial dysfunction and lung cellular senescence are significant features involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) stands as the primary contributing factor to COPD. This study examined mitochondrial dynamics, mitophagy and lung cellular senescence in COPD patients and investigated the effects of modulation of mitochondrial fusion [mitofusin2 (MFN2) and Optic atrophy 1 (OPA1)] on CS extract (CSE)-induced lung cellular senescence. Methods Senescence-associated secretory phenotype (SASP) component mRNAs (IL-1β, IL-6, CXCL1 and CXCL8), mitochondrial morphology, mitophagy and mitochondria-related proteins (including phosphorylated-DRP1(p-DRP1), DRP1, MFF, MNF2, OPA1, PINK1, PARK2, SQSTM1/p62 and LC3b) and senescence-related proteins (including P16, H2A.X and Klotho) were measured in lung tissues or primary alveolar type II (ATII) cells of non-smokers, smokers and COPD patients. Alveolar epithelial (A549) cells were exposed to CSE with either pharmacologic inducer (leflunomide and BGP15) or genetic induction of MFN2 and OPA1 respectively. Results There were increases in mitochondrial number, and decreases in mitochondrial size and activity in lung tissues from COPD patients. SASP-related mRNAs, DRP1 phosphorylation, DRP1, MFF, PARK2, SQSTM1/p62, LC3B II/LC3B I, P16 and H2A.X protein levels were increased, while MFN2, OPA1, PINK1 and Klotho protein levels were decreased in lung tissues from COPD patients. Some similar results were identified in primary ATII cells of COPD patients. CSE induced increases in oxidative stress, SASP-related mRNAs, mitochondrial damage and dysfunction, mitophagy and cellular senescence in A549 cells, which were ameliorated by both pharmacological inducers and genetic overexpression of MFN2 and OPA1. Conclusions Impaired mitochondrial fusion, enhanced mitophagy and lung cellular senescence are observed in the lung of COPD patients. Up-regulation of MFN2 and OPA1 attenuates oxidative stress, mitophagy and lung cellular senescence, offering potential innovative therapeutic targets for COPD therapy. Graphical Abstract

Background Large cell neuroendocrine carcinoma (LCNEC) is a rare high-grade neuroendocrine carcinoma of the lung. Little is known about the differences between the pure and combined LCNEC subtypes, and thus we conducted this study to provide more comprehensive insight into LCNEC. Methods We reviewed 221 patients with pure LCNEC (P-LCNEC) and 120 patients with combined LCNEC (C-LCNEC) who underwent pulmonary surgery in our hospital to compare their clinical features, driven genes’ status ( EGFR/ALK/ROS1/KRAS/BRA F), and adjuvant chemotherapy regimens. Propensity score matching (PSM) was applied to reduce selection bias. Results The P-LCNEC group included a higher proportion of males and smokers than the C-LCNEC group. Furthermore, the C-LCNEC group had higher incidences of visceral pleural invasion (VPI), EGFR mutation and ALK rearrangement compared with the P-LCNEC group. Expression of neuroendocrine markers (CD56, CGA, and SYN) and recurrence patterns were not significantly different between the two groups. The P-LCNEC group had better disease-free survival (DFS) and overall survival (OS) compared with the C-LCNEC group (median DFS: 67.0 vs. 28.1 months, p = 0.021; median OS: 72.0 vs. 45.0 months, p = 0.001), which was further confirmed by the PSM method ( p = 0.004 and p < 0.001, respectively). Adjuvant chemotherapy was also an independent factor for DFS and OS. Subgroup analysis found that regardless of whether it was for the entire LCNEC group or the P- and C-LCNEC subtypes, the small cell lung cancer (SCLC) regimens presented with superior survival compared with the non-small cell lung cancer (NSCLC) regimens. Conclusion P-LCNEC was associated with more favorable prognosis compared with C-LCNEC. SCLC-based adjuvant chemotherapy was more appropriate for LCNEC patients than NSCLC-based regimens, regardless of whether they were the pure or combined LCNEC subtypes. C-LCNEC patients may be the potential beneficiary of targeted therapy.

Although clear cell renal cell carcinoma (ccRCC) is easy to diagnose early and most can be radically resected, nearly one-third of patients still experience metastases after radical nephrectomy. The most common distant metastases sites of ccRCC are lung, bone and liver. However, periampullary metastasis of ccRCC is very rare and easy to misdiagnose. A 59-year-old male patient was hospitalized for recurrent hematochezia. He had a history of nephrectomy 16 years ago due to ccRCC. Enhanced upper abdominal computed tomography (CT) suggested a mass in the ampulla of vater, and active hemorrhage of duodenal papilla was observed by endoscopy. He underwent an emergency pancreaticoduodenectomy because endoscopic hemostasis and transcatheter arterial embolization (TAE) both failed. Intraoperatively, we found that the tumor located in the ampulla and invaded the pancreatic tissue. The operation was successful, with no postoperative complications. Postoperative pathology suggested metastatic ccRCC.

Paclitaxel is widely used to treat cancer patients through the blocking of mitosis, yet results in formation of polyploidy giant cancer cells (PGCCs), which are generally believed to be non-dividing cells.

Background: With the popularization of high-resolution computed tomography (HRCT), the detection rate of synchronous multiple primary lung cancer (SMPLC) is increasing. We retrospectively analyzed the surgical results of SMPLC patients in our hospital to determine the best treatment, surgical prognosis and survival analysis.Methods: A total of 78 SMPLC patients met the diagnostic criteria underwent complete resection and lymph node dissection or sampling without any preoperative induction therapy in the Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University. We analyzed the postoperative survival rate, and further studied the relationship between survival rates and sex, age, preoperative symptoms, tumor location, tumor number, tumor size, lymph node metastasis, TNM stage, surgical type, surgical frequency, histopathologic types, vascular infiltration, visceral pleural invasion and postoperative therapy.Results: Among 78 patients, the 1-,2-,3-,4- and 5-year disease free survival (DFS) rates were 93.42%, 86.84%, 77.78%, 62.96%, and 60.00%, respectively, while the 1-,2-,3-,4- and 5-year overall survival (OS) rates were 94.73%, 92.11%, 82.22%, 77.78%, and 65.00%, respectively. TNM stage of the largest tumor (II:HR=7.40,III:9.01,p=0.002) was an independent risk factor for DFS. Smoking history (HR=4.34,p=0.039) and TNM stage of the largest tumor (II:HR=9.38,III:9.42,p=0.003) were independent risk factors for overall survival.Conclusions: First, SMPLC is different from intrapulmonary metastasis and its clinical stage is also different from the 8th (2015) edition TNM classification for lung cancer. Second, when pulmonary function permits, surgery (complete resection and lymph node dissection) is a significantly beneficial treatment for patients with SMPLC. Third, TNM stage of the largest tumor (II:HR=7.40,III:9.01,p=0.002) was an independent risk factor for DFS. Smoking history (HR=4.34,p=0.039) and TNM stage of the largest tumor (II:HR=9.38,III:9.42,p=0.003) were independent risk factors for overall survival.

As a negative external product of China's rapid development, haze pollution has seriously affected the quality of economic development and people's quality of life. This paper firstly explores the important reasons for the uncoordinated industrial structure caused by haze pollution, and puts forward the purpose of promoting the adjustment of industrial structure through urban governance in order to tackle with the urgent problem of haze pollution. Using panel data from 287 cities in China, this paper analyzes the relationship among industrial structure, urban governance and haze pollution using the Geographically and Temporally Weighted Regression (GTWR) model. The innovations are: (1) this paper focuses on the topic of industrial structure, urban governance and haze pollution simultaneously. (2) this paper uses the method of GTWR to comprehensively consider the spatial and temporal tendency at the same time. (3) Conclusions are helpful to provide targeted policy recommendations. And the results show that: (1) the spatial clustering characteristics of haze pollution are very prominent, and have been suppressed to a certain extent under the measures of urban governance; (2) the spatial and temporal differences of industrial structure on haze pollution are large; (3) corporate governance plays an important role in slowing down haze pollution; (4) in public governance, the green coverage rate of built-up areas, the innocuous disposal rate of domestic garbage and the increase of public transport will have a negative impact on haze pollution, while highly concentrated urban population, high level of economic development, large number of industrial enterprises above designated size, and increased thermal power generation capacity will increase the degree of haze pollution; (5) cities with steadily decreasing of the proportion of the secondary industry, the proportion of the tertiary industry, the comprehensive treatment rate of industrial solid materials, the green coverage rate of the built-up area and the industrial enterprises above designated size are mainly lie in southeastern China, respectively; and cities with decline in innocuous disposal rate of domestic garbage are concentrated in the western region, while cities with significant changes of the number of buses per unit are mainly distributed in the northeastern region, the other variables are not obvious.

BACKGROUND:Medical institutions worldwide have not reached a consensus on what surgery is the most advisable for pulmonary typical carcinoid (TC) patients at the localized stage. This research focuses on exploring whether wedge resection or segmental resection is the superior option.METHODS:The demographic and clinical information of 1,887 TC patients diagnosed at the localized stage from 2004 to 2015 was collected from the Surveillance, Epidemiology, and End Results (SEER) Program. Patient prognosis was evaluated by KM curves. The chi-square test was used to examine the variation between different groups that would be eliminated by propensity score matching (PSM). Univariate and multivariate Cox proportional hazard model analyses were used to evaluate prognostic values of relative factors.RESULTS:The prognosis of TC was the most favorable for patients suffering from pulmonary squamous cell carcinoma (SCC), adenocarcinoma (ADC), and pulmonary carcinoids (PCs). The choice to have surgery, not the type of surgery chosen, was the most significant independent prognostic factor correlated with overall survival (OS) and lung cancer-special survival (LCSS). The prognostic result of the comparison between wedge resection and segmental resection was not statistically significant before or after PSM. In subgroup analysis, the inference still held.

Background Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum-etoposide) in treatment-naive patients with ES-SCLC. Methods This randomised, open-label, phase 3 trial was done at 209 sites across 23 countries. Eligible patients were adults with untreated ES-SCLC, with WHO performance status 0 or 1 and measurable disease as per Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were randomly assigned (in a 1:1:1 ratio) to durvalumab plus platinum-etoposide; durvalumab plus tremelimumab plus platinum-etoposide; or platinum-etoposide alone. All drugs were administered intravenously. Platinum-etoposide consisted of etoposide 80-100 mg/m(2) on days 1-3 of each cycle with investigator's choice of either carboplatin area under the curve 5-6 mg/mL per min or cisplatin 75-80 mg/m(2) (administered on day 1 of each cycle). Patients received up to four cycles of platinum-etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks in the immunotherapy groups and up to six cycles of platinum-etoposide every 3 weeks plus prophylactic cranial irradiation (investigator's discretion) in the platinum-etoposide group. The primary endpoint was overall survival in the intention-to-treat population. We report results for the durvalumab plus platinumetoposide group versus the platinum-etoposide group from a planned interim analysis. Safety was assessed in all patients who received at least one dose of their assigned study treatment. This study is registered at ClinicalTrials.gov, NCT03043872, and is ongoing. Findings Patients were enrolled between March 27, 2017, and May 29, 2018. 268 patients were allocated to the durvalumab plus platinum-etoposide group and 269 to the platinum-etoposide group. Durvalumab plus platinumetoposide was associated with a significant improvement in overall survival, with a hazard ratio of 0.73 (95% CI 0.59-0.91; p=0.0047]); median overall survival was 13.0 months (95% CI 11.5-14.8) in the durvalumab plus platinum-etoposide group versus 10.3 months (9.3-11.2) in the platinum-etoposide group, with 34% (26.9-41.0) versus 25% (18.4-31.6) of patients alive at 18 months. Any-cause adverse events of grade 3 or 4 occurred in 163 (62%) of 265 treated patients in the durvalumab plus platinum-etoposide group and 166 (62%) of 266 in the platinumetoposide group; adverse events leading to death occurred in 13 (5%) and 15 (6%) patients. Interpretation First-line durvalumab plus platinum-etoposide significantly improved overall survival in patients with ES-SCLC versus a clinically relevant control group. Safety findings were consistent with the known safety profiles of all drugs received. Copyright (C) 2019 Elsevier Ltd. All rights reserved.