Thoracic Cancer最新文献

{"title":"Identifying Lipid Metabolism-Related Therapeutic Targets and Diagnostic Markers for Lung Adenocarcinoma by Mendelian Randomization and Machine Learning Analysis.","authors":"Su Wei, Zhou Guangyao, Tian Xiangdong, Guo Feng, Zhang Lianmin, Zhang Zhenfa","doi":"10.1111/1759-7714.70020","DOIUrl":"10.1111/1759-7714.70020","url":null,"abstract":"<p><strong>Background: </strong>Lipid metabolic disorders are emerging as a recognized influencing factors of lung adenocarcinoma (LUAD). This study aims to investigate the influence of lipid metabolism-related genes (LMRGs) on the diagnosis and treatment of LUAD and to identify significant biomarkers.</p><p><strong>Methods: </strong>DESeq2 and robust rank aggregation (RRA) analyses were employed to determine the differential expression of LMRGs from TCGA-LUAD and five GEO datasets. Mendelian randomization (MR) was conducted utilizing protein quantitative trait loci (pQTLs) in the deCODE, prot-a, and UKB-PPP Study to estimate causal relationships between plasma proteins and LUAD within the ieu-a-984, ieu-a-965, and FinnGen R10 cohorts as potential drug targets of LUAD. Subsequently, an optimal machine learning model for diagnosing LUAD was established by comparing four models: support vector machine, random forest (RF), glmBoost, and eXtreme Gradient Boosting. Finally, the diagnostic performance of five plasma proteins was validated through nomogram analysis, calibration curve assessment, decision curve analysis (DCA), independent internal and external datasets.</p><p><strong>Result: </strong>A total of five biomarkers were identified from 1034 LMRGs via MR and differential expression analysis. TNFRSF21 exhibited a positive association with LUAD risk; conversely, BCHE, FABP4, LPL, and PLBD1 demonstrated negative correlations with this risk. The RF machine learning model was determined to be the optimal model for diagnosing LUAD using these five plasma proteins. Ultimately, nomogram construction, calibration curve analysis, DCA, as well as independent internal and external dataset validation confirmed that these biomarkers exhibit excellent diagnostic performance.</p><p><strong>Conclusions: </strong>BCHE, FABP4, LPL, PLBD1, and TNFRSF21 represent potential novel reliable diagnostic markers as well as therapeutic targets for LUAD.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 6","pages":"e70020"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diosmetin Inhibits NETs Formation in Neutrophils Through Regulating Nrf2 Signaling.","authors":"Lijuan Guo, Hongyang Luo, Yuxin Lei, Leiyan Gu, Yaohui Wang, Siyuan Wang, Zihan Lian, Yuhao Li, Yanlan Xiang, Guanhua Du, Rui Shao, Xiaoxuan Tian, Han Zhang, Linjie Shen, Junli Chen, Yi Wang, Ning Huang, Xiaoyu Niu, Jingyu Li","doi":"10.1111/1759-7714.70040","DOIUrl":"10.1111/1759-7714.70040","url":null,"abstract":"<p><strong>Background: </strong>Neutrophil extracellular traps (NETs) are important pieces of equipment for neutrophils. Excess NETs play promoting roles in cancer-associated thrombosis (CAT). Therefore, directing NETs formation is a promising therapeutic strategy in thrombosis and related diseases. Diosmetin, an antioxidant flavonoid derived from dietary sources, might be involved in NETs formation and CAT.</p><p><strong>Methods: </strong>Firstly, the tests of cell-free DNA and Immunofluorescence were applied to evaluate the NETs levels of neutrophils. Luminol-based chemiluminescence and the DCFH-DA probe were used to detect the levels of reactive oxygen species (ROS) in neutrophils. Then, network pharmacological analysis and molecular docking were used to predict potential target molecules of diosmetin. The RT-qPCR was performed to measure the levels of Nrf2 and HO-1. A series of functional assays of neutrophils were used to examine the effect of diosmetin on other neutrophil functions. Finally, an animal model of deep vein thrombosis was constructed to assess the effect of diosmetin on thrombosis.</p><p><strong>Results: </strong>Diosmetin reduced NETs and ROS levels in neutrophils. Then, molecular mechanisms analysis suggested that Nrf2 might be the primary target of diosmetin. Diosmetin treatment increased the levels of Nrf2 and HO-1 in NETs-generating neutrophils. An inhibitor of Nrf2 diminished the negative effect of diosmetin on NETs generation. Lastly, the murine thrombosis model results indicated that diosmetin treatment reduced thrombosis via NETs formation.</p><p><strong>Conclusion: </strong>Diosmetin exerts as anti-NETs effect through Nrf2 signaling in neutrophils, showing the therapeutic potential in thromboembolism and related pathological processes, such as CAT.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 6","pages":"e70040"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-Stage Bilateral Pulmonary Nodule Resection via Unilateral Thoracic Cavity Access: A Single-Center Experience of 12 Cases.","authors":"Zhen Wang, Zhaolei You, Yingjian Song, Hua Ji, Guodong Jiang, Xiaokun Bu, Jingyu Zhang, Tengfei Yi, Jian Fang, Xiaofeng Yu","doi":"10.1111/1759-7714.70053","DOIUrl":"10.1111/1759-7714.70053","url":null,"abstract":"<p><strong>Background: </strong>Surgical intervention remains the primary therapeutic modality for managing multiple pulmonary nodules. However, in cases with bilateral pulmonary nodules, one-stage bilateral resection is discouraged due to tumor aggressiveness and surgical invasiveness. In light of this, we investigated an innovative approach, termed one-stage bilateral pulmonary nodule resection via unilateral thoracic cavity access.</p><p><strong>Methods: </strong>From July 2022 to September 2024, a cohort of 12 patients with bilateral pulmonary nodules were enrolled in this study. This technique involves initial unilateral transcostal incision for segmental or lobectomy of a nodule on one side, followed by bilateral mediastinal pleura incision through the anterior mediastinum, facilitating subsequent wedge resection of the contralateral nodule. Clinical and pathological data, along with perioperative imaging findings and follow-up information, were systematically collected and subjected to a comprehensive retrospective analysis.</p><p><strong>Results: </strong>A total of 25 nodules were resected from 12 patients. Regarding surgical approaches, nine patients underwent right thoracic incision, while three patients underwent left thoracic incision. Intraoperatively, seven patients received bilateral wedge resections, whereas five patients underwent segmentectomy on one side combined with wedge resection on the contralateral side. R0 resection of the contralateral nodules was successfully achieved during the procedures. The average distance between the surgical margin and the contralateral nodules was 12.5 mm, ranging from 5 mm to 25 mm. Of the 12 patients, one (Patient 6) was lost to follow-up, while the remaining 11 patients underwent postoperative chest CT examinations. The median follow-up duration for these 11 patients was 105 days (range: 36-857 days). No evidence of bilateral pleural effusion or tumor recurrence was detected on follow-up chest CT scans.</p><p><strong>Conclusions: </strong>This study offers the potential to concurrently address bilateral pulmonary nodules, thereby sparing patients from the need for a subsequent hospitalization for surgical intervention.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 6","pages":"e70053"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung Adenocarcinoma With Initially Co-Occurring EGFR and BRAF Double Mutation: A Case Report and Literature Review.","authors":"Lu Wang, Xueting Wang, Motong Xu, Yanan Wang, Lingxin Feng, Xue Yang, Jing Wang","doi":"10.1111/1759-7714.70031","DOIUrl":"10.1111/1759-7714.70031","url":null,"abstract":"<p><p>Vrafmurine sarcoma viral oncogene homolog B (BRAF) mutations, including both V600E and non-V600E variants, are infrequent in non-small cell lung cancer (NSCLC), representing approximately 2% of lung adenocarcinomas. Activated BRAF mutations are regarded as an underappreciated oncogenic driver in NSCLC, typically occurring in a mutually exclusive manner with epidermal growth factor receptor (EGFR) mutations, as well as ALK and ROS1 rearrangements. In recent years, advancements in multiple-gene panel testing have demonstrated that EGFR mutations and BRAF mutations can coexist. Notably, the secondary BRAF V600E mutation has been identified as one of the mechanisms contributing to resistance against EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated lung adenocarcinomas. However, the role of co-occurring BRAF mutations and associated treatment strategies in patients with EGFR mutations has not been thoroughly investigated. Additionally, the profile of adverse events related to combination therapy has not been previously evaluated. This case report presents a patient with co-occurring EGFR and BRAF mutations who demonstrated a sustained response and tolerance to adverse events when treated with a combination of Osimertinib, Trametinib, and Dabrafenib.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 5","pages":"e70031"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Efficacy and Safety of Lenvatinib in Advanced or Recurrent Thymic Carcinoma: A Multicenter Retrospective Study in Japan.","authors":"Satoshi Miyamoto, Akihiro Tsukaguchi, Hanako Kuhara, Taiichiro Otsuki, Takayuki Shiroyama, Motohiro Tamiya, Akihiro Tamiya, Kazumi Nishino, Yoshito Takeda, Takashi Kijima, Meinoshin Okumura, Atsushi Kumanogoh, Masahide Mori","doi":"10.1111/1759-7714.70047","DOIUrl":"10.1111/1759-7714.70047","url":null,"abstract":"<p><strong>Background: </strong>Lenvatinib is recommended for the treatment of advanced and recurrent thymic carcinomas. However, there is a paucity of data on lenvatinib's use in real-world clinical practice. The aim of this study was to evaluate the efficacy and safety of lenvatinib in patients with thymic carcinoma.</p><p><strong>Methods: </strong>This multicenter retrospective cohort study assessed the efficacy and tolerability of lenvatinib in the treatment of patients with advanced or recurrent thymic carcinoma between March 2021 and March 2024.</p><p><strong>Results: </strong>Twenty-seven patients from six institutions in Japan were enrolled in this study. The median progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were 9.0 months (95% confidence interval [CI] 4.8-14.5), 33% (95% CI 16.5%-54%), and 85% (95% CI 66.3%-95.8%), respectively. Although the number of patients was small, the median PFS of the first-, second-, and third- or later-line treatment groups was 21.3 months (n = 5), 9.0 months (n = 13), and 5.8 months (n = 9) (p = 0.171), respectively. Dose reduction was required in all patients, with 17 (63%) presenting grade ≥ 3 adverse events, including hypertension in seven patients and proteinuria in six. No grade ≥ 4 adverse events were observed.</p><p><strong>Conclusion: </strong>The real-world efficacy and safety of lenvatinib are consistent with those reported in previous clinical trials of second-line lenvatinib. Furthermore, despite the relatively small sample size, our findings suggest that lenvatinib may be effective for the treatment of thymic carcinoma.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 6","pages":"e70047"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-Generation Sequencing vs. Clinical-Pathological Assessment in Diagnosis of Multiple Lung Cancers: A Systematic Review and Meta-Analysis.","authors":"Ziyang Wang, Xiaoqiu Yuan, Yuntao Nie, Jun Wang, Guanchao Jiang, Kezhong Chen","doi":"10.1111/1759-7714.70039","DOIUrl":"10.1111/1759-7714.70039","url":null,"abstract":"<p><p>Accurately distinguishing between multiple primary lung cancers (MPLC) and intrapulmonary metastasis (IPM) is crucial for tailoring treatment strategies and improving patient outcomes. While molecular methods offer significant advantages over traditional clinical-pathological evaluations, they lack standardized diagnostic protocols and validated prognostic value. This study systematically compared the diagnostic and prognostic performance of molecular methods versus clinical-pathological evaluations in diagnosing multiple lung cancers (MLCs), specifically focusing on the impact of next-generation sequencing (NGS) parameters on diagnostic accuracy. A review of 41 studies encompassing 1266 patients revealed that two molecular methods, Mole1 (manually counting shared mutations) and Mole2 (bioinformatics-assisted clonal probability calculation), both demonstrated superior diagnostic accuracy and prognostic discrimination capabilities. Molecular assessment, particularly Mole1, effectively stratified prognosis for MPLC and IPM, leading to significantly improved disease-free survival (DFS: HR = 0.24, 95% CI: 0.15-0.39) and overall survival (OS: HR = 0.33, 95% CI: 0.18-0.58). Further analysis suggests that a minimal panel of 30-50 genes may be sufficient to effectively differentiate prognoses. Compared to Mole1, Mole2 demonstrated greater specificity and stability across various panels, achieving AUC values from 0.962 to 0.979. Clinical-pathological evaluations proved unreliable, not only failing to distinguish prognosis effectively but also exhibiting a potential misdiagnosis rate of 35.5% and 33.6% compared to the reference diagnosis. To improve both cost-effectiveness and diagnostic accuracy, bioinformatics-assisted molecular diagnostics should be integrated into multidisciplinary assessments, especially for high-risk cases where diagnostic errors are common.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 6","pages":"e70039"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Radiotherapy Combined With Sintilimab in Advanced NSCLC Patients Who Progressed on First or Second Line Therapy: A Prospective, Multiple Center, and Single-Arm Study.","authors":"Xiaoyi Feng, Xiaoyan Liu, Hui Guan, Chunhong Chen, Feng Gao, Xiaoxing Gao, Minjiang Chen, Jing Zhao, Yan Xu, Mengzhao Wang","doi":"10.1111/1759-7714.70043","DOIUrl":"10.1111/1759-7714.70043","url":null,"abstract":"<p><strong>Background: </strong>This study explored the safety and efficacy of combining radiotherapy with sintilimab in non-small cell lung cancer (NSCLC) patients who have progressed after first or second-line therapy.</p><p><strong>Methods: </strong>In this multicenter, single-arm trial, patients with NSCLC who had progressed after first or second-line therapy were enrolled. Participants received hypofractionated stereotactic body radiotherapy (SBRT) (requiring a single-site biological dose of more than 30 Gy or planned to reach 30 Gy) followed by sintilimab every 3 weeks until disease progression or unacceptable toxicity occurred.</p><p><strong>Results: </strong>From March 1, 2019, to July 27, 2023, 14 patients were enrolled across two centers. The cohort included 64.3% males and 35.7% females, with a median age of 67 years (range 57-73 years). All participants completed radiation therapy and received at least one cycle of sintilimab. The overall response rate (ORR) was 21.4% (3/14) and the disease control rate (DCR) was 71.4% (10/14). The absent radiation response (ARR) was 14.3% (2/14). The median PFS was 4.17 months (95% CI: 1.15-8.69 months), with a 6-month PFS rate of 42.9%. The median OS was 16.17 months (95% CI: 11.69-20.64 months). Overall, 10 patients (71.4%) experienced at least one treatment-emergent adverse event (TEAE). Grade 3 adverse events included one case each of immune-related myocarditis, thrombocytopenia, and checkpoint inhibitor pneumonitis (CIP). Four patients (28.6%) had immune-related adverse events (irAEs) including skin rash and pruritus (2/14, grade 1), immune-related myocarditis (1/14, grade 3), and CIP (1/14, grade 3).</p><p><strong>Conclusions: </strong>Radiotherapy combined with sintilimab for NSCLC patients who progressed after first-or second-line therapy showed promising efficacy outcomes.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 6","pages":"e70043"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACT001 Suppresses the Malignant Progression of Small-Cell Lung Cancer by Inhibiting Lactate Production and Promoting Anti-Tumor Immunity.","authors":"Xiao-Jing Ding, Ting Mei, Xiao-Nan Xi, Jing-Ya Wang, Wen-Jing Wang, Yue Chen, Ya-Xin Lu, Ting-Ting Qin, Ding-Zhi Huang","doi":"10.1111/1759-7714.70028","DOIUrl":"10.1111/1759-7714.70028","url":null,"abstract":"<p><strong>Background: </strong>Improving the \"cold\" tumor immune microenvironment (TIME) of small-cell lung cancer (SCLC) represents a promising therapeutic approach. The metabolite lactate plays a crucial role in shaping the immune-cold tumor microenvironment (TME) and facilitating tumor progression. Phosphoglycerate kinase 1 (PGK1) is a key enzyme involved in tumor lactate metabolism. This study demonstrates that ACT001 improves the TIME of SCLC through inhibiting lactate production by targeting PGK1.</p><p><strong>Methods: </strong>The cytotoxic effects of ACT001 on SCLC cell lines NCI-H1688 and NCI-H446 were evaluated using MTT assay, clone formation, EdU incorporation, wound healing, and invasion assays. To elucidate the mechanism of action of ACT001, proteomic techniques, pull-down assays, LC-MS/MS, surface plasmon resonance, immunofluorescence, lactate generation, glucose uptake, and western blot assays were conducted. A xenograft model was used to assess the in vivo anti-tumor activity of ACT001.</p><p><strong>Results: </strong>ACT001 inhibited the proliferation, invasion, and metastasis of SCLC both in vitro and in vivo. Additionally, it reduced lactate accumulation and M2 macrophage polarization. Mechanistically, ACT001 released micheliolide, which covalently modified Cys316 of PGK1 under physiological conditions. This suppressed PGK1 activity and restored the distribution of PGK1 in mitochondria and the cytoplasm under hypoxic conditions.</p><p><strong>Conclusions: </strong>ACT001 inhibits the malignant progression of SCLC by suppressing lactate production, modulating macrophage polarization, and restraining tumor metastasis through PGK1 targeting.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 5","pages":"e70028"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inherent PD-L1 22C3 Expression in Alveolar Macrophages Impacts the Combined Positive Score Status in Breast Cancer With Pulmonary Metastasis.","authors":"Yoon Jin Cha, Hye Min Kim, Ja Seung Koo","doi":"10.1111/1759-7714.70004","DOIUrl":"10.1111/1759-7714.70004","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to determine the impact of inherent programmed death-ligand 1 (PD-L1)-expressing alveolar macrophages (AMs) on the combined positive score (CPS) of PD-L1 (22C3) in metastatic breast cancer in the lungs.</p><p><strong>Methods: </strong>A total of 87 patients with pulmonary metastases of breast cancer were included in this study. Immunohistochemical staining of various PD-L1 antibodies was performed. The CPSs and CPSs excluding the number of PD-L1 positive AMs [CPS(NAM)s] with PD-L1 (22C3) were determined and compared.</p><p><strong>Results: </strong>Among 87 enrolled patients, 22 had luminal A breast cancer, 24 had luminal B breast cancer, 13 had HER-2-positive breast cancer, and 28 had triple-negative breast cancer (TNBC). CPSs ≥ 10 was observed only in luminal B (12.5%) and TNBC (35.7%) subtypes (p < 0.001), whereas CPS(NAM)s ≥ 10 was observed only in TNBC (14.3%) (p = 0.011). Changes from the CPS-positive to the CPS(NAM)-negative status occurred in nine cases (10.3%), with significantly higher proportions being observed in the luminal B (12.5%) and TNBC (21.4%) subtypes (p = 0.007). Tumors showing changes from the CPS-positive to the CPS(NAM)-negative status were larger (p < 0.001); similar findings were observed in the TNBC subgroup (p = 0.001).</p><p><strong>Conclusion: </strong>The inclusion of PD-L1 expressing AMs leads to differences in CPS positivity, especially in large TNBC subtype tumors.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 5","pages":"e70004"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NSUN4 Facilitates the Activity of Oncogenic Protein CDC20 to Promote NSCLC Development by Mediating m5C Modification of CDC20 mRNA.","authors":"Zhilong Li, Xianzhen Wu","doi":"10.1111/1759-7714.70023","DOIUrl":"10.1111/1759-7714.70023","url":null,"abstract":"<p><strong>Background: </strong>5-methylcytosine (m5C) methylation is the crucial posttranscriptional modification of RNA. NSUN4, a methyltransferase for m5C methylation, contributes to lung tumorigenesis. Here, we determined the precise action of NSUN4 on the development of non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>NSUN4 and CDC20 mRNA expression was detected by quantitative PCR. Western blot and immunohistochemistry were used for the analysis of protein expression. Cell growth, apoptosis, invasiveness, migratory ability, and stemness potential were evaluated by colony formation, flow cytometry, transwell, and sphere formation assays. The influence of NSUN4 in CDC20 mRNA was analyzed using RNA immunoprecipitation (RIP) assay and Actinomycin D (Act D) treatment. Subcutaneous xenograft studies were performed to analyze the function in vivo.</p><p><strong>Results: </strong>In human NSCLC tumors and cell lines, NSUN4 and CDC20 levels were upregulated. NSUN4 inhibition diminished NSCLC cell growth, stemness, invasiveness, and migratory ability in vitro, while NSUN4 increase had opposite effects. A positive expression association between CDC20 and NSUN4 was observed in NSCLC samples. Mechanistically, NSUN4 enhanced the stability of CDC20 mRNA through m5C modification. CDC20 depletion significantly counteracted NSUN4-driven cell phenotype alterations in vitro. Additionally, inhibition of NSUN4 impeded the growth of A549 NSCLC subcutaneous xenografts in vivo.</p><p><strong>Conclusion: </strong>Our findings identify the pro-tumorigenic property of the NSUN4/CDC20 cascade in NSCLC. Targeting the novel cascade may be a promising way for combating this deadly disease.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 5","pages":"e70023"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}