Translational lung cancer research最新文献

{"title":"DNA damage and repair (DDR) gene mutation profiles in driver gene wild-type advanced non-small cell lung cancer and the predictive role of response to platinum-based chemotherapy.","authors":"Tianxiu Wu, Yu Xu, Qiuyue Song, Xiuqing Liao, Wei Yao, Guangsong Wang, Yu Yang, Bin Wang, Liang Guo, Mingzhou Zhang, Guoming Wu, Li Luo, Li Bai, Yan Wang, Mingdong Hu, Zhi Xu","doi":"10.21037/tlcr-24-972","DOIUrl":"10.21037/tlcr-24-972","url":null,"abstract":"<p><strong>Background: </strong>Platinum-based chemotherapy is an important therapeutic approach for patients with advanced non-small cell lung cancer (NSCLC) without driver gene mutations. DNA damage and repair (DDR) gene can mitigate platinum-induced DNA damage and induce resistance to platinum agents. The status of DDR gene in advanced driver gene wild-type NSCLC and their role in determining response and prognosis to platinum-based chemotherapy need to be investigated. This study used next-generation sequencing (NGS) to detect the mutation status of 47 DDR genes in seven DDR signaling pathways in driver gene wild-type NSCLC patients and to investigate their association with cisplatin-based chemotherapy.</p><p><strong>Methods: </strong>From November 2016 to September 2021, 182 cases of treatment-naïve patients with advanced driver gene wild-type NSCLC were prospectively studied. Either tumor tissue or serum circulating tumor DNA (ctDNA) was used to assess the status of 47 DDR gene using NGS. The primary endpoint was objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS) and overall survival (OS). The DDR mutation was analyzed in relation to response to platinum-based chemotherapy and clinical outcomes.</p><p><strong>Results: </strong>There were 136 of 182 patients who received first-line platinum-based chemotherapy included. DDR mutations from 101 NSCLC patients were sequenced and analyzed. The median follow-up time was 17.6 (interquartile range, 15.4-19.8) months. There were 66.33% of patients in this cohort having a DDR gene mutation. When treated with first-line platinum-based chemotherapy, the ORR of DDR-mutant (DDRmut) patients was significantly higher than that of DDR-wild type (DDRwt) patients (52.2% <i>vs.</i> 23.5%, P<0.001). In addition, DDRmut patients experienced longer PFS (6.30 <i>vs.</i> 3.30 months, P<0.001) and improved OS (16.80 <i>vs.</i> 9.40 months, P=0.007).</p><p><strong>Conclusions: </strong>There was a high prevalence of DDR mutation in advanced NSCLC harboring wild-type epidermal growth factor receptor (<i>EGFR</i>)/anaplastic lymphoma kinase (<i>ALK</i>)/ROS proto-oncogene 1 (<i>ROS1</i>). DDR deficiency, manifested by an alteration in 47-gene DDR panel readout, is a favorable predictive biomarker for first-line platinum-based chemotherapy in patients with advanced NSCLC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1089-1103"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094242","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":"Integrative radiomics analysis of peri-tumoral and habitat zones for predicting major pathological response to neoadjuvant immunotherapy and chemotherapy in non-small cell lung cancer.","authors":"Dan Han, Junfeng Zhao, Shaoyu Hao, Shenbo Fu, Ran Wei, Xin Zheng, Qian Zhao, Chengxin Liu, Hongfu Sun, Chengrui Fu, Zhongtang Wang, Wei Huang, Baosheng Li","doi":"10.21037/tlcr-2024-1131","DOIUrl":"10.21037/tlcr-2024-1131","url":null,"abstract":"<p><strong>Background: </strong>It is crucial for clinical decision-making to identify non-small cell lung cancer (NSCLC) patients who are likely to achieve major pathological response (MPR) following neoadjuvant immunotherapy and chemotherapy (NICT). This study conducted a thorough analysis of the regions surrounding and within resectable NSCLC tumors, creating an integrative tumor microenvironment model that encompasses features of both the peri-tumoral areas and habitat-based subregions, aiming at enhancing accurate predictions and supporting clinical decision-making processes.</p><p><strong>Methods: </strong>Our study involved an analysis of 243 NSCLC patients from three centers, treated with NICT and surgery and categorized into training, validation, and test cohorts. We conducted an extensive analysis of the tumor area, examining the intra-tumoral zone and the surrounding peri-tumoral regions at 2 mm, 4 mm and 6 mm, developing an algorithm for delineating tumor habitats. Features were standardized with Z-scores and de-duplicated by retaining one from each highly correlated pair. We finalized the feature set using least absolute shrinkage and selection operator (LASSO) regression and 10-fold cross-validation, forming a robust radiomics signature for machine learning models. Clinical features underwent univariable and multivariable analyses, combining with peri-tumoral and habitat signatures in a nomogram, of which its diagnostic accuracy and clinical utility were evaluated using receiver operating characteristic (ROC), calibration curves, and decision curve analysis (DCA).</p><p><strong>Results: </strong>The cohort showed a 68% MPR rate, with histology identified as a key predictor. An integrated nomogram including histology, Peri6mm and habitat signatures outperformed individual models with an area under the curve (AUC) of 0.894 in the training cohort, 0.831 in validation and 0.799 in testing. The nomogram demonstrated a clear advantage in predictive probabilities, as evidenced by DCA curve results.</p><p><strong>Conclusions: </strong>Our study's development of a predictive model using a nomogram integrating clinical and radiomics features significantly improved MPR prediction in NSCLC patients undergoing NICT, enhancing clinical decision-making.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1168-1184"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094936","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":"<i>FOXO3a</i> regulation of non-small cell lung cancer radiotherapy resistance through the <i>PINK1/Parkin</i> pathway of protective mitophagy.","authors":"Xiaoting Wu, Litang Huang, Lu Meng, Shilan Luo, Paola Anna Jablonska, Chi Zhang, Anqi Zhang, Peng Li, Xiaomei Gong","doi":"10.21037/tlcr-2025-181","DOIUrl":"10.21037/tlcr-2025-181","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy resistance has become one of the major causes of radiotherapy failure among patients with non-small cell lung cancer (NSCLC), but its underlying mechanism remains unclear. In recent years, the influence of mitochondrial autophagy on the radiotherapy resistance in treated tumor cells and its regulatory mechanism has become a hotspot in research, which is also the subject of our group research effort. The primary objective of our study is to investigate the mitophagy-associated pathway and the regulatory mechanisms underlying radiotherapy resistance in NSCLC.</p><p><strong>Methods: </strong>We developed biologically stable radiotherapy-resistant NSCLC cell models A549/X and H520/X and verified the radioresistance of these cells. Subsequently, through high-throughput transcriptomic sequencing analysis and experimental verification, we found that the Forkhead box O 3a (<i>FOXO3a</i>) gene and the <i>PINK1/Parkin</i> mitochondrial autophagy pathway in NSCLC radiotherapy-resistant cell lines were consistent and upregulated more reactively than those of parent cells. The effect of gene expression status of the <i>FOXO3a-PINK1/Parkin</i> pathway on the survival outcomes of NSCLC was analyzed in The Cancer Genome Atlas (TCGA) database. Next, we inoculated nude mouse xenografts with small interfering RNA to interfere with the FOXO3a gene and short hairpin RNA to construct radiotherapy-resistant stable strains of NSCLC with stable knockdown of <i>FOXO3a</i> gene. Subsequently, the association and regulation of <i>FOXO3a</i> gene expression levels with radioresistance and mitochondrial autophagy <i>PINK1/Parkin</i> pathway at the cellular and animal levels were determined.</p><p><strong>Results: </strong>The expression level of <i>FOXO3a</i> gene in NSCLC radioresistant cells was significantly positively correlated with the level of mitophagy and the expression level of <i>PINK1/Parkin</i> pathway. Higher expression levels of genes in the <i>FOXO3a-PINK1/Parkin</i> pathway had a negative effect on survival outcomes in NSCLC and were positively correlated with the radioresistance of cells.</p><p><strong>Conclusions: </strong><i>FOXO3a</i> regulates NSCLC radioresistance by modulating the mitochondrial autophagy <i>PINK1/Parkin</i> pathway, which may serve as a new molecular intervention target and therapeutic entry point for intervening and improving the radioresistance of patients with NSCLC in clinical practice.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1320-1339"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094887","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":"Integrating radiomics and deep learning for enhanced prediction of high-grade patterns in stage IA lung adenocarcinoma.","authors":"Zhongxiao Chen, Hao Liu, Hua Sun, Cheng Xu, Bingyu Hu, Luyu Qu, William C Cho, Thivanka Witharana, Chengchu Zhu, Jianfei Shen","doi":"10.21037/tlcr-24-995","DOIUrl":"10.21037/tlcr-24-995","url":null,"abstract":"<p><strong>Background: </strong>The presence of high-grade patterns (HGPs) often has a detrimental effect on prognosis. It is helpful to make individualized clinical treatment plans when preoperative recognition of the presence of HGPs becomes possible. So, this study aimed to develop a model based on preoperative computed tomography (CT) images to predict the presence of HPGs in invasive pulmonary non-mucinous adenocarcinoma.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 403 surgically treated patients with clinical stage IA and pathologically confirmed invasive non-mucinous adenocarcinoma. There were 256 deep learning features and 1,836 handcrafted features extracted from the regions of interest (ROIs) in preoperative CT images. The optimal subset of features was screened using <i>t</i>-test, Pearson correlation analysis, and least absolute shrinkage and selection operator (LASSO) regression to construct the fusion model. Receiver operating characteristic (ROC) curve was applied to assess the model's performance. Decision curve analysis (DCA) and calibration curve were used to assess the clinical usefulness.</p><p><strong>Results: </strong>The fusion model combining radiomics features and deep learning features using the XGBoost classifier exhibited strong predictive efficacy with the area under the curve (AUC) of 0.983, 0.862, and 0.832 in the training, validation, and test set. It means that the model can distinguish well between tumors with and without HGPs. The fusion model had better diagnostic performance when compared to the radiomics model and deep learning model. Calibration curve indicated good coherence between model prediction and the actual observation. DCA revealed the fusion model exerted the highest clinical benefit.</p><p><strong>Conclusions: </strong>The fusion model can identify the presence of HPGs in invasive lung adenocarcinoma from preoperative CT images. It assists clinicians in determining individualized treatments and monitoring strategies for patients.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1076-1088"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094952","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":"Budesonide/glycopyrronium/formoterol fumarate co-suspension metered dose inhaler relieves cough after lobectomy: a randomized controlled study.","authors":"Junguo Dong, Shunjun Jiang, Yuan Qiu, Jingpei Li, Fei Cui, Hengrui Liang, Shen Lao, Zixian Xie, Jun Huang, Zhexue Hao, Huanghe He, Xin Xv, Man Zhang, Miao He, Yuan Zhang, Jianxing He, Wei Wang","doi":"10.21037/tlcr-24-905","DOIUrl":"10.21037/tlcr-24-905","url":null,"abstract":"<p><strong>Background: </strong>Cough after pulmonary resection (CAP) has emerged as a prevalent complication. However, existing treatment protocols for CAP lack standardization. The components of the budesonide/glycopyrronium/formoterol fumarate co-suspension metered dose inhaler (BGF MDI) have been consistently documented for their effectiveness in cough management. Consequently, we initiated this clinical trial to evaluate the efficacy and safety of BGF MDI in mitigating CAP.</p><p><strong>Methods: </strong>Enrolled participants exhibited no pre-existing cough before undergoing lobectomy. The patients were randomly assigned in a 1:1 ratio to either the BGF MDI group or the Control group. The BGF MDI group received BGF MDI for 14 consecutive days postoperatively; each participant in both groups underwent continuous follow-up for 60 days. Cough severity, duration, and cough-related quality of life were evaluated. The primary endpoints were focused on the occurrence of obvious CAP lasting ≥14 days.</p><p><strong>Results: </strong>Finally, 51 patients in the BGF MDI group and 52 patients in the Control group were included in the analysis after accounting for dropout. The BGF MDI group demonstrated a reduction in the incidence of obvious CAP lasting ≥14 days (13.7% <i>vs</i>. 40.4%). The cough-related quality of life for the BGF MDI group on the 14th and 30th days after surgery was higher. Three participants in the BGF MDI group reported palpitations, with no other complications noted.</p><p><strong>Conclusions: </strong>BGF MDI has shown efficacy and safety in reducing CAP severity and duration. Using BGF MDI after lobectomy helps to alleviate cough symptoms and speed up postoperative recovery.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov. Clinical Trial Registry Number: NCT05472350.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1290-1300"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094990","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":"Characterization of the xeno-GVHD response generated by advanced lung cancer patient peripheral blood mononuclear cells in NSG-SGM3 mice.","authors":"Vered Fuchs, Laila Roisman, Maha Msamra, Yael Refaely, Aharon Yehonatan Cohen, Angel Porgador, Nir Peled, Ariel Sobarzo","doi":"10.21037/tlcr-24-787","DOIUrl":"10.21037/tlcr-24-787","url":null,"abstract":"<p><strong>Background: </strong>Peripheral blood mononuclear cell (PBMC) humanized mouse models are essential for researching non-small cell lung cancer (NSCLC) treatments. However, these models are prone to xeno-graft versus host disease (xeno-GVHD), hampering their utility and requiring further investigation. This study examined xeno-GVHD responses from PBMCs of advanced-stage NSCLC patients compared to healthy donors (HDs) in a humanized peripheral blood lymphocyte (hu-PBL) model.</p><p><strong>Methods: </strong>PBMCs from NSCLC patients and HDs were injected into immunocompromised NSG-SGM3 mice and monitored for eight weeks. xeno-GVHD progression was assessed through clinical examinations and flow cytometry of human T-cell levels in various tissues.</p><p><strong>Results: </strong>Mice injected with PBMCs from HDs showed xeno-GVHD signs as early as 28 days post-injection, whereas those from NSCLC patients exhibited minimal signs, with only one model showing delayed responses by day 42. Clinical symptoms in mice included weight loss, anemia, low platelet counts, fur changes, and behavioral modifications. Flow cytometry of human PBMCs in mice indicated dominant CD8⁺ effector memory T cells in peripheral blood. In contrast, CD4⁺ effector memory T cells were predominant in the organs, with overall T cell levels lower in NSCLC models.</p><p><strong>Conclusions: </strong>This study demonstrates significant differences in xeno-GVHD progression between advance-stage NSCLC patients and HDs, likely influenced by the patient's treatment histories. These findings improve our understanding of hu-PBL models for NSCLC research and may inform future treatment studies and strategies.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1301-1319"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095005","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":"Clinical implication of tumor spread through air spaces in stage IA lung adenocarcinoma: prognostic impact and association with the International Association for the Study of Lung Cancer (IASLC) grade.","authors":"Jinghan Shi, Kuan Xu, Xufeng Liu, Martin P Barr, Jeffrey B Velotta, Ninh M La-Beck, Chenxi Zhong, Feng Yao","doi":"10.21037/tlcr-2025-253","DOIUrl":"10.21037/tlcr-2025-253","url":null,"abstract":"<p><strong>Background: </strong>Tumor spread through air spaces (STAS) and a new histological grading system proposed by the International Association for the Study of Lung Cancer (IASLC) have been studied for risk stratification and prognostic assessment in patients with lung adenocarcinoma (LUAD). This study aimed to clarify the association between STAS and IASLC grade and to assess the prognostic significance of STAS in patients with pathological stage (p-stage) IA LUAD as stratified by the IASLC grading system.</p><p><strong>Methods: </strong>This study included 789 patients with resected p-stage IA LUAD treated between 2018 and 2020. Logistic regression analysis was performed to assess the association between STAS and clinicopathological characteristics. A Cox proportion hazards model was used to assess the risk factors related to recurrence-free survival (RFS) and overall survival (OS).</p><p><strong>Results: </strong>STAS was present in 242 patients (30.7%). The independent factors associated with the presence of STAS were nodule type [odds ratio (OR) =3.89; 95% confidence interval (CI): 2.69-5.62; P<0.001], IASLC grade (grade 2: OR =12.41, 95% CI: 3.83-40.23; P<0.001; grade 3: OR =27.35, 95% CI: 8.24-90.82, P<0.001), and lymphovascular invasion (OR =3.30; 95% CI: 1.72-6.35; P<0.001). For all patients (N=789), STAS and IASLC grade were independent prognostic factors for RFS and OS. For grade 2 LUAD, p-stage T1c was an independent prognostic factor for RFS [hazard ratio (HR) =4.30, 95% CI: 1.07-19.08; P=0.045] and OS (HR =4.95, 95% CI: 1.14-21.54; P=0.03). STAS was significantly correlated with unfavorable RFS (HR =2.81; 95% CI: 1.32-5.97; P=0.007) and OS (HR =2.04, 95% CI: 1.40-7.75; P=0.006) in patients with grade 3 tumors.</p><p><strong>Conclusions: </strong>The presence of STAS was not only directly correlated with the IASLC grading system, but was also a prognostic factor for worse RFS and OS in grade 3 LUAD patients.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1384-1394"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095006","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":"Exosomal miR-182-5p is a potential diagnostic marker for malignant pleural effusion.","authors":"Wen Zhao, Jian-Xun Wen, Yan Niu, Li Yan, Mei-Ying Wang, Wei Jiao, Ya-Fei Wang, Wen-Hui Gao, Dan-Ni Yang, Wen-Qi Zheng, Zhi-De Hu","doi":"10.21037/tlcr-2024-1205","DOIUrl":"10.21037/tlcr-2024-1205","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers in pleural fluid are the potential auxiliary diagnostic markers for malignant pleural effusion (MPE). Exosomal microRNAs (miRNAs) represent novel diagnostic markers for various diseases. The diagnostic performance of exosomal miRNAs for MPE remains unclear. Therefore, we examined the exosomal miRNAs profiles of both MPE and benign pleural effusion (BPE), aiming to study diagnostic performance of exosomal miRNAs for MPE.</p><p><strong>Methods: </strong>We used next-generation sequencing (NGS) technology to analyze the pleural fluid exosomal miRNA profile in five MPE and 15 BPE cases. We analyzed the differentially expressed exosomal miRNAs by reverse transcription polymerase chain reaction (RT-PCR), with cel-miR-39 or snRNA U6 as internal references. We assessed the diagnostic accuracy of exosomal miRNA for MPE with a receiver operating characteristic (ROC) curve. We also analyzed whether exosomal miRNA could improve the diagnostic performance of pleural carcinoembryonic antigen (CEA).</p><p><strong>Results: </strong>Fifty-eight miRNAs were up-regulated, and 35 miRNAs were down-regulated in MPE. We selected exosomal miR-182-5p for further study and analyzed miR-182-5p in 153 patients with undiagnosed pleural effusion. Exosomal miR-182-5p was undetectable in 32 participants. In the remaining participants with 49 MPE and 72 BPE cases, we found that the areas under the curve (AUCs) and their 95% confidence intervals (95% CIs) for exosomal miR-182-5p were 0.78 (95% CI: 0.69-0.86) when using cel-miR-39 as an internal reference, and 0.80 (95% CI: 0.73-0.88) when using snRNA U6. The combination of exosomal miR-182-5p and CEA can slightly improve the diagnostic accuracy of MPE, with an AUC of 0.91 (95% CI: 0.85-0.97).</p><p><strong>Conclusions: </strong>Pleural miR-182-5p can assist in the diagnosis of MPE. Its diagnostic performance is slightly affected by internal reference.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1138-1148"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094832","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":"Metabolic tumor volume on ¹⁸F-FDG uptake as a negative predictor after ipilimumab plus nivolumab in advanced non-small cell lung cancer.","authors":"Kosuke Hashimoto, Kyoichi Kaira, Atsuto Mouri, Ayako Shiono, Yu Miura, Ou Yamaguchi, Hisao Imai, Hiroshi Kagamu, Ichiei Kuji","doi":"10.21037/tlcr-2024-1084","DOIUrl":"10.21037/tlcr-2024-1084","url":null,"abstract":"<p><strong>Background: </strong>Nivolumab plus ipilimumab (Nivo-Ipi) is a standard treatments for metastatic or recurrent non-small cell lung cancer (NSCLC). Unlike programmed death-1 (PD-1) inhibitor monotherapy, the possible predictors of Nivo-Ipi treatment effectiveness remain unclear. Therefore, this retrospective study evaluated the prognostic relevance of 2-deoxy-2-[fluorine-18]-fluoro-d-glucose positron emission tomography (¹⁸F-FDG PET) after Nivo-Ipi treatment in patients with advanced NSCLC.</p><p><strong>Methods: </strong>Among 130 eligible patients with metastatic or recurrent NSCLC who received Nivo-Ipi as initial treatment and underwent ¹⁸F-FDG PET prior to the initial treatment, the maximum standardized uptake value (SUV_max), SUV_peak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on ¹⁸F-FDG uptake were evaluated.</p><p><strong>Results: </strong>High MTV and TLG on ¹⁸F-FDG uptake were significantly associated with poor performance status (PS), no response, high neutrophil-to-leukocyte ratio (NLR), low albumin levels, and high C-reactive protein (CRP) level, while SUV_max and SUV_peak showed no significant associations. Univariate analysis of all patients identified PS, bone metastases, NLR, MTV, and TLG as significant predictors of prognosis. By multivariate analysis, NLR and MTV were identified as independent predictors of prognosis. Sub-analysis based on histology and programmed death ligand-1 (PD-L1) expression identified MTV as an independent prognostic predictor for Nivo-Ipi treatment in patients with histological findings of adenocarcinoma (AC) and PD-L1 <1%. A high MTV with poor outcome was closely associated with a poor PS, lymph node metastases, bone metastases, high NLR, low albumin levels, and high CRP level.</p><p><strong>Conclusions: </strong>MTV determined based on ¹⁸F-FDG uptake was a negative prognostic factor after Nivo-Ipi treatment, particularly in patients with histological findings of AC or PD-L1 <1%.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1242-1253"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094874","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":"Using human genetics to understand the epidemiological association between neuroticism and lung cancer.","authors":"Dongsheng Wu, Yongcheng Liu, Shuqiao Liu, Xiaohu Hao, Xin Li, Quan Zheng, Tengyong Wang, Yuchen Huang, Shiyou Wei, Jian Zhou, Lunxu Liu","doi":"10.21037/tlcr-24-950","DOIUrl":"10.21037/tlcr-24-950","url":null,"abstract":"<p><strong>Background: </strong>Neuroticism, a personality trait characterized by emotional instability, has been linked to an increased risk of lung cancer (LC). However, the genetic underpinnings of this association remain poorly understood. This study aimed to comprehensively dissect the genetic link underlying neuroticism and LC.</p><p><strong>Methods: </strong>We used genome-wide association study (GWAS) data to investigate the intricate genetic relationship between neuroticism and LC, along with specific histological subtypes: lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and small-cell LC (SCLC). Our analytical framework encompassed global and local genetic correlation, cross-trait meta-analysis, transcriptome-wide association study (TWAS), and bidirectional Mendelian randomization (MR) analysis.</p><p><strong>Results: </strong>Notable genetic correlations were found between neuroticism and overall LC (r_g=0.15, P=2.24×10^-5), with stronger associations observed for LUSC (r_g=0.21, P=3.39×10^-6) and SCLC (r_g=0.16, P=2.50×10^-3). Partitioning the genome revealed additional genetic correlations in specific local genomic regions (including chr6q27 and chr6q16.2-q16.3) and functional categories (such as H3K27ac and H3K9ac). The cross-trait meta-analysis revealed 24 genetic loci that influenced both traits, including four novel ones. Looking into the gene-tissue level, TWAS identified 35 genes associated with both neuroticism and LC across multiple tissues, particularly in the nervous, respiratory, cardiovascular, and endocrine systems. MR analysis indicated a potential causal effect of neuroticism on overall LC [odds ratio (OR) =1.48, P=5.53×10^-4] and LUSC (OR =1.52, P=8.00×10^-3), but not on LUAD or SCLC. No reverse causality was observed.</p><p><strong>Conclusions: </strong>This study reveals a genetic link between neuroticism and LC, offering new insights into LC risk assessment and potential prevention strategies for individuals with high neuroticism levels.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1104-1117"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095024","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}