Translational lung cancer research最新文献

{"title":"Correlation analysis between driver gene mutation and clinicopathological features in lung adenocarcinoma based on real-world cumulative clinical data.","authors":"Sheng Lu, Aotian Guo, Haichuan Hu, Xinxin Ying, Yao Li, Zhengwei Huang, Wangjue Xu, Shen Tao, Xiaotong Hu, Na Yan, Xuan Zhang, Dan Shen, Takaaki Sasaki, Surein Arulananda, Ken Onodera, Zhengfu He","doi":"10.21037/tlcr-24-409","DOIUrl":"10.21037/tlcr-24-409","url":null,"abstract":"<p><strong>Background: </strong>Driver genes are essential predictors of targeted therapeutic efficacy. Detecting driver gene mutations in lung adenocarcinoma (LUAD) patients can help to screen for targeted drugs and improve patient survival benefits. This study aims to investigate the mutation characterization of driver genes and their correlation with clinicopathological features in LUAD.</p><p><strong>Methods: </strong>A total of 440 LUAD patients were selected from Sir Run Run Shaw Hospital between July 2019 and September 2022. Postoperative tissue specimens were analyzed for gene mutations using next-generation sequencing technology, focusing, including epidermal growth factor receptor <i>EGFR, ALK, ROS1, RET, KRAS, MET, BRAF, HER2, PIK3CA</i> and <i>NRAS</i>. At the same time, clinicopathological data were collected and organized for multidimensional correlation analysis.</p><p><strong>Results: </strong>Of 440 LUAD patients, driver gene mutations were not detected in 48 patients. The proportion of patients with driver gene mutations was as high as 89.09%. The top three driver genetic mutations were <i>EGFR, KRAS</i>, and <i>MET</i>. Sixty-nine types of <i>EGFR</i> mutations were detected and distributed in the protein tyrosine kinase catalytic domain (56, 81.16%), Furin-like cysteine-rich region (9, 13.04%), receptor binding domain (3, 4.35%), and <i>EGFR</i> transmembrane domain (1, 1.45%). Single gene locus mutation occurred in 343 LUAD patients, but the mutation gene types covered all tested genes. Our findings showed that <i>EGFR</i> mutations were more commonly observed in non-smoking and female patients (P<0.01), <i>KRAS</i> mutations were more prevalent in male patients and smokers (P<0.01), ROS1 mutations had larger tumor diameters (P<0.01) and <i>RET</i> mutations were more prevalent in smokers (P<0.05).</p><p><strong>Conclusions: </strong>LUAD patients exhibit diverse genetic mutations, which may co-occur simultaneously. Integrated analysis of multiple mutations is essential for accurate diagnosis and effective treatment of the disease. The use of NGS can significantly expand our understanding of gene mutations and facilitate integrated analysis of multiple gene mutations, providing critical evidence for targeted treatment methods.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis and treatment of non-small cell lung cancer (NSCLC) harboring <i>MET</i> Ex14 skipping: have we met the desired drug?","authors":"Go Makimoto","doi":"10.21037/tlcr-24-93","DOIUrl":"10.21037/tlcr-24-93","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting <i>MET</i> exon 14 skipping mutation in pulmonary sarcomatoid carcinoma by whole-tumour texture analysis combined with clinical and conventional contrast-enhanced computed tomography features.","authors":"Lei Miao, Tian Qiu, Yan Li, Jianwei Li, Xu Jiang, Mengwen Liu, Xue Zhang, Jiuming Jiang, Huanhuan Zhang, Yanmei Wang, Xiao Li, Jianming Ying, Meng Li","doi":"10.21037/tlcr-24-56","DOIUrl":"10.21037/tlcr-24-56","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary sarcomatoid carcinoma (PSC) is a rare, highly malignant type of non-small cell lung cancer (NSCLC) with a poor prognosis. Targeted drugs for <i>MET</i> exon 14 (<i>MET</i>ex14) skipping mutation can have considerable clinical benefits. This study aimed to predict <i>MET</i>ex14 skipping mutation in PSC patients by whole-tumour texture analysis combined with clinical and conventional contrast-enhanced computed tomography (CECT) features.</p><p><strong>Methods: </strong>This retrospective study included 56 patients with PSC diagnosed by pathology. All patients underwent CECT before surgery or other treatment, and both targeted DNA- and RNA-based next-generation sequencing (NGS) were used to detect <i>MET</i>ex14 skipping mutation status. The patients were divided into two groups: <i>MET</i>ex14 skipping mutation and nonmutation groups. Overall, 1,316 texture features of the whole tumour were extracted. We also collected 12 clinical and 20 conventional CECT features. After dimensionality reduction and selection, predictive models were established by multivariate logistic regression analysis. Models were evaluated using the area under the curve (AUC), and the clinical utility of the model was assessed by decision curve analysis.</p><p><strong>Results: </strong><i>MET</i>ex14 skipping mutation was detected in 17.9% of PSCs. Mutations were found more frequently in those (I) who had smaller long- or short-axis diameters (P=0.02, P=0.01); (II) who had lower T stages (I, II) (P=0.02); and (III) with pseudocapsular or annular enhancement (P=0.03). The combined model based on the conventional and texture models yielded the best performance in predicting <i>MET</i>ex14 skipping mutation with the highest AUC (0.89). The conventional and texture models also had good performance (AUC =0.83 conventional; =0.88 texture).</p><p><strong>Conclusions: </strong>Whole-tumour texture analysis combined with clinical and conventional CECT features may serve as a noninvasive tool to predict the <i>MET</i>ex14 skipping mutation status in PSC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive value of delta-radiomic features for prognosis of advanced non-small cell lung cancer patients undergoing immune checkpoint inhibitor therapy.","authors":"Xiaoyu Han, Yujin Wang, Xi Jia, Yuting Zheng, Chengyu Ding, Xiaohui Zhang, Kailu Zhang, Yunkun Cao, Yumin Li, Liming Xia, Chuansheng Zheng, Jing Huang, Heshui Shi","doi":"10.21037/tlcr-24-7","DOIUrl":"10.21037/tlcr-24-7","url":null,"abstract":"<p><strong>Background: </strong>No robust predictive biomarkers exist to identify non-small cell lung cancer (NSCLC) patients likely to benefit from immune checkpoint inhibitor (ICI) therapies. The aim of this study was to explore the role of delta-radiomics features in predicting the clinical outcomes of patients with advanced NSCLC who received ICI therapy.</p><p><strong>Methods: </strong>Data of 179 patients with advanced NSCLC (stages IIIB-IV) from two institutions (Database 1 =133; Database 2 =46) were retrospectively analyzed. Patients in the Database 1 were randomly assigned into training and validation dataset, with a ratio of 8:2. Patients in Database 2 were allocated into testing dataset. Features were selected from computed tomography (CT) images before and 6-8 weeks after ICI therapy. For each lesion, a total of 1,037 radiomic features were extracted. Lowly reliable [intraclass correlation coefficient (ICC) <0.8] and redundant (r>0.8) features were excluded. The delta-radiomics features were defined as the relative net change of radiomics features between two time points. Prognostic models for progression-free survival (PFS) and overall survival (OS) were established using the multivariate Cox regression based on selected delta-radiomics features. A clinical model and a pre-treatment radiomics model were established as well.</p><p><strong>Results: </strong>The median PFS (after therapy) was 7.0 [interquartile range (IQR): 3.4, 9.1] (range, 1.4-13.2) months. To predict PFS, the model established based on the five most contributing delta-radiomics features yielded Harrell's concordance index (C-index) values of 0.708, 0.688, and 0.603 in the training, validation, and testing databases, respectively. The median survival time was 12 (IQR: 8.7, 15.8) (range, 2.9-23.3) months. To predict OS, a promising prognostic performance was confirmed with the corresponding C-index values of 0.810, 0.762, and 0.697 in the three datasets based on the seven most contributing delta-radiomics features, respectively. Furthermore, compared with clinical and pre-treatment radiomics models, the delta-radiomics model had the highest area under the curve (AUC) value and the best patients' stratification ability.</p><p><strong>Conclusions: </strong>The delta-radiomics model showed a good performance in predicting therapeutic outcomes in advanced NSCLC patients undergoing ICI therapy. It provides a higher predictive value than clinical and the pre-treatment radiomics models.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The combination of osimertinib and savolitinib as molecular inhibition of EGFR and MET receptors may be selected to provide maximum effectiveness and acceptable toxicity.","authors":"Dariusz M Kowalski, Magdalena Zaborowska-Szmit, Sebastian Szmit, Piotr Jaśkiewicz, Maciej Krzakowski","doi":"10.21037/tlcr-24-204","DOIUrl":"10.21037/tlcr-24-204","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptidyl-prolyl isomerase F as a prognostic biomarker associated with immune infiltrates and mitophagy in lung adenocarcinoma.","authors":"Zitong Feng, Lin Yuan, Luyuan Ma, Wenhao Yu, Fayez Kheir, Lukas Käsmann, Wolfgang M Brueckl, Kai Jin, Dingxin Wang, Yi Shen, Rongyang Li, Hui Tian","doi":"10.21037/tlcr-24-344","DOIUrl":"10.21037/tlcr-24-344","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is among the most prevalent malignancies worldwide, with unfavorable treatment outcomes. Peptidyl-prolyl isomerase F (<i>PPIF</i>) is known to influence the malignancy traits of tumor progression by modulating the bioenergetics and mitochondrial permeability in cancer cells; however, its role in LUAD remains unclear. Our study seeks to investigate the clinical significance, tumor proliferation, and immune regulatory functions of <i>PPIF</i> in LUAD.</p><p><strong>Methods: </strong>The expression of <i>PPIF</i> in LUAD tissues and cells was assessed using bioinformatics analysis, immunohistochemistry (IHC), and Western blotting. Survival curve analysis was conducted to examine the prognostic association between <i>PPIF</i> expression and LUAD. The immunomodulatory role of <i>PPIF</i> in LUAD was assessed through the analysis of <i>PPIF</i> expression and immune cell infiltration. A series of gain- and loss-of-function experiments were conducted on <i>PPIF</i> to investigate its biological functions in LUAD both <i>in vitro</i> and <i>in vivo</i>. The mechanisms underlying <i>PPIF</i>'s effects on LUAD were delineated through functional enrichment analysis and Western blotting assays.</p><p><strong>Results: </strong><i>PPIF</i> exhibited overexpression in LUAD tissues compared to normal controls. Survival curve analysis revealed that patients with LUAD exhibiting higher <i>PPIF</i> expression demonstrated decreased overall survival and a shorter progression-free interval. <i>PPIF</i> was implicated in modulating immune cell infiltration, particularly in regulating the T helper 1-T helper 2 cell balance. Functionally, <i>PPIF</i> was discovered to promote tumor cell proliferation and advance cell-cycle progression. Furthermore, <i>PPIF</i> could impede mitophagy by targeting the FOXO3a/PINK1-Parkin signaling pathway.</p><p><strong>Conclusions: </strong>The findings of this study indicate that the prognosis-related gene <i>PPIF</i> may have a significant role in the regulation of LUAD cell proliferation, tumor-associated immune cell infiltration, and mitophagy, and thus <i>PPIF</i> may be a promising therapeutic target of LUAD.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics analysis of an immunotherapy responsiveness-related gene signature in predicting lung adenocarcinoma prognosis.","authors":"Yupeng Jiang, Bacha Hammad, Hong Huang, Chenzi Zhang, Bing Xiao, Linxia Liu, Qimi Liu, Hengxing Liang, Zhenyu Zhao, Yawen Gao","doi":"10.21037/tlcr-24-309","DOIUrl":"10.21037/tlcr-24-309","url":null,"abstract":"<p><strong>Background: </strong>Immune therapy has become first-line treatment option for patients with lung cancer, but some patients respond poorly to immune therapy, especially among patients with lung adenocarcinoma (LUAD). Novel tools are needed to screen potential responders to immune therapy in LUAD patients, to better predict the prognosis and guide clinical decision-making. Although many efforts have been made to predict the responsiveness of LUAD patients, the results were limited. During the era of immunotherapy, this study attempts to construct a novel prognostic model for LUAD by utilizing differentially expressed genes (DEGs) among patients with differential immune therapy responses.</p><p><strong>Methods: </strong>Transcriptome data of 598 patients with LUAD were downloaded from The Cancer Genome Atlas (TCGA) database, which included 539 tumor samples and 59 normal control samples, with a mean follow-up time of 29.69 months (63.1% of patients remained alive by the end of follow-up). Other data sources including three datasets from the Gene Expression Omnibus (GEO) database were analyzed, and the DEGs between immunotherapy responders and nonresponders were identified and screened. Univariate Cox regression analysis was applied with the TCGA cohort as the training set and GSE72094 cohort as the validation set, and least absolute shrinkage and selection operator (LASSO) Cox regression were applied in the prognostic-related genes which fulfilled the filter criteria to establish a prognostic formula, which was then tested with time-dependent receiver operating characteristic (ROC) analysis. Enriched pathways of the prognostic-related genes were analyzed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and tumor immune microenvironment (TIME), tumor mutational burden, and drug sensitivity tests were completed with appropriate packages in R (The R Foundation of Statistical Computing). Finally, a nomogram incorporating the prognostic formula was established.</p><p><strong>Results: </strong>A total of 1,636 DEGs were identified, 1,163 prognostic-related DEGs were extracted, and 34 DEGs were selected and incorporated into the immunotherapy responsiveness-related risk score (IRRS) formula. The IRRS formula had good performance in predicting the overall prognoses in patients with LUAD and had excellent performance in prognosis prediction in all LUAD subgroups. Moreover, the IRRS formula could predict anticancer drug sensitivity and immunotherapy responsiveness in patients with LUAD. Mechanistically, immune microenvironments varied profoundly between the two IRRS groups; the most significantly varied pathway between the high-IRRS and low-IRRS groups was ribonucleoprotein complex biogenesis, which correlated closely with the <i>TP53</i> and <i>TTN</i> mutation burdens. In addition, we established a nomogram incorporating the IRRS, age, sex, clinical stage, T-stage, N-stage, and M-stage as predictors","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radical resection in a patient with stage IIIA non-small cell lung cancer with the <i>EGFR</i> exon 19 deletion mutation after neoadjuvant targeted therapy with osimertinib: a case report.","authors":"Hao Chen, Jiarong Zhang, Atsushi Osoegawa, Lorenzo Calvetti, Palma Fedele, Chun Chen, Bin Zheng","doi":"10.21037/tlcr-24-403","DOIUrl":"10.21037/tlcr-24-403","url":null,"abstract":"<p><strong>Background: </strong>With the advent of targeted therapies, the survival rates of patients with locally advanced lung cancer have significantly improved. However, there is limited research on the efficacy of neoadjuvant targeted therapy in resectable advanced non-small cell lung cancer (NSCLC) patients with positive driver genes. This article reports a case of stage IIIA NSCLC with an epidermal growth factor receptor (<i>EGFR</i>) 19del mutation that successfully underwent radical lung cancer surgery following neoadjuvant targeted therapy. By observing the perioperative treatment outcomes and side effects in this patient, we aimed to provide insights and summarize experiences for treating similar cases in the future.</p><p><strong>Case description: </strong>We report a case of a 54-year-old female diagnosed preoperatively with stage IIIA adenocarcinoma of the left upper lung (cT1cN2M0). The patient's course was complicated by acute sick sinus syndrome and was cured by implanting a permanent pacemaker. After multidisciplinary discussion, it was decided to administer neoadjuvant targeted therapy with osimertinib. Following 6 weeks of treatment, the tumor assessment showed partial response (PR), making the patient eligible for surgery. The patient underwent single-port thoracoscopic left upper lobectomy + mediastinal lymphadenectomy. Intraoperatively, the left hilar lymph nodes were found to be tightly adherent to the apical-anterior branch of the left upper pulmonary artery. The main trunk of the left pulmonary artery was temporarily occluded with a vascular clamp to safely dissect the left upper pulmonary artery. The procedure was completed without conversion to open thoracotomy, achieving an R0 resection. Postoperative pathology confirmed stage IIIA (ypT1bN2M0), and the patient continued adjuvant therapy with osimertinib.</p><p><strong>Conclusions: </strong>Neoadjuvant targeted therapy with osimertinib is expected to become one of the options for neoadjuvant therapy in locally advanced NSCLC with sensitizing <i>EGFR</i> mutations. And for those with advanced lung cancer involving tumors close to the hilum or mediastinal lymph node metastasis, preblocking of the left upper pulmonary artery can help improve surgical safety and better ensure R0 resection.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between strenuous sports or other exercises and lung cancer risk: a mendelian randomization study.","authors":"Wushu Chen, Anlin Liu, Yu Jiang, Yuechun Lin, Xingpei Li, Chongde Pan, Yixuan Wang, Huiwen Yu, Yulin Zhao, Junxing Li, Hengrui Liang, Runchen Wang, Wei Wang, Xin Xu, Ying Huang","doi":"10.21037/tlcr-23-810","DOIUrl":"10.21037/tlcr-23-810","url":null,"abstract":"<p><strong>Background: </strong>Studying the relationship between strenuous sports or other exercises (SSOE) and lung cancer risk remains underexplored. Traditional observational studies face challenges like confounders and inverse causation. However, Mendelian randomization (MR) provides a promising approach in epidemiology and genetics, using genetic variants as instrumental variables to investigate causal relationships. By leveraging MR, we have scrutinized the causal link between SSOE and lung cancer development.</p><p><strong>Methods: </strong>Twelve single-nucleotide polymorphisms (SNPs) associated with SSOE, as identified in previously published genome-wide association studies, were utilized as instrumental variables in our investigation. Summary genetic data at the individual level were obtained from relevant studies and cancer consortia. The study encompassed a total of 11,348 cases and 15,861 controls. The statistical technique of inverse variance-weighting (IVW), commonly employed in meta-analyses and MR studies, was employed to assess the causal relationship between SSOE and lung cancer risk.</p><p><strong>Results: </strong>The MR risk analysis indicated a causal relationship between SSOE and the incidence of lung cancer, with evidence of a reduced risk for overall lung cancer [odds ratio (OR) =0.129; 95% confidence interval (CI): 0.021-0.779; P=0.03], lung adenocarcinoma (OR =0.161; 95% CI: 0.012-2.102; P=0.16) and squamous cell lung cancer (OR =0.045; 95% CI: 0.003-0.677; P=0.03). The combined OR for lung cancer from SSOE (controlling for waist circumference and smoking status) was 0.054 (95% CI: 0.010-0.302, P<0.001).</p><p><strong>Conclusions: </strong>Our MR analysis findings indicate a potential correlation between SSOE and a protective effect against lung cancer development. Further investigation is imperative to uncover the precise mechanistic link between them.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PSME3 promotes lung adenocarcinoma development by regulating the TGF-β/SMAD signaling pathway.","authors":"Shuai Wang, Yongmeng Li, Kai Jin, Kenichi Suda, Rongyang Li, Huiying Zhang, Hui Tian","doi":"10.21037/tlcr-24-340","DOIUrl":"10.21037/tlcr-24-340","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is one of the most common types of cancer worldwide. Proteasome activator subunit 3 (PSME3) is a subunit of a proteasome activator, and changes in PSME3 can lead to the development of many diseases in organisms. However, the specific mechanism of PSME3 in LUAD has not yet been elucidated. This study initially revealed the mechanism of PSME3 promoting the progression of lung adenocarcinoma, which provided a potential molecular target for clinical treatment.</p><p><strong>Methods: </strong>PSME3 expression in LUAD cells and tissues was assessed by bioinformatics analysis, immunohistochemistry (IHC), Western blotting (WB), and quantitative real time polymerase chain reaction (qRT-PCR). A series of functional experiments were used to evaluate the effects of PSME3 knockdown and overexpression on LUAD cell proliferation, migration, and apoptosis. The potential mechanism of PSME3 was explored by transcriptome sequencing and WB experiments.</p><p><strong>Results: </strong>In this study, our initial findings indicated that PSME3 expression was abnormally high in LUAD and was associated with poor patient prognosis. Further, we found that the downregulation of PSME3 significantly inhibited LUAD cell proliferation, an effect that was verified by subcutaneous tumor formation experiments in nude mice. Similarly, the rate of invasion and migration of LUAD cells significantly decreased after the downregulation of PSME3. Using flow cytometry, we found that the knockdown of PSME3 caused cell cycle arrest at the G1/S phase. Through transcriptome sequencing, we found that the transforming growth factor-beta (TGF-β)/SMAD signaling pathway was closely related to LUAD, and we then validated the pathway using WB assays.</p><p><strong>Conclusions: </strong>We demonstrated that PSME3 was abnormally highly expressed in LUAD and related to poor patient prognosis; therefore, targeting PSME3 in the treatment of LUAD may represent a novel therapeutic approach.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}