Clinical Respiratory Journal最新文献

{"title":"Study Protocol of the Korean EGFR Registry: A Multicenter Prospective and Retrospective Cohort Study in Nonsmall Cell Lung Cancer Patients With EGFR Mutation.","authors":"Chang Dong Yeo, Dong Won Park, Seong Hoon Yoon, Eun Young Kim, Jeong Eun Lee, Shin Yup Lee, Chang-Min Choi, In-Jae Oh, Do Jin Kim, Jeong Seon Ryu, Jae Cheol Lee, Young-Chul Kim, Tae Won Jang, Kye Young Lee, Seung Hun Jang, Seung Joon Kim","doi":"10.1111/crj.70043","DOIUrl":"https://doi.org/10.1111/crj.70043","url":null,"abstract":"<p><strong>Introduction: </strong>The provision of treatment for epidermal growth factor receptor (EGFR)-mutated nonsmall cell lung cancer (NSCLC) patients has increased in Korea. However, multicenter studies on the clinicopathologic dataset and treatment outcomes, using a large-scale dataset, have not been conducted. The current study is a prospective and retrospective multicenter observational cohort study that registers all stages of EGFR-mutated NSCLC patients.</p><p><strong>Methods: </strong>The Korean EGFR Registry was designed to enroll 2000 patients with all stages of EGFR-mutated NSCLC from 40 university hospitals across Korea. This study, encompassing both retrospective and prospective cohorts, aims to analyze clinical characteristics, treatment modalities, and outcomes in these patients. Data collection will include patient demographics, smoking history, quality of life assessments, pathological data, and treatment outcomes, with follow-up until December 2026. The primary endpoint is disease-free survival in patients who have undergone radical therapy (surgery and radiotherapy) or progression-free survival in those receiving targeted therapy (first, second, and subsequent lines), chemotherapy (first and subsequent lines), combination therapy, and palliative/maintenance therapy according to stages of EGFR-mutated NSCLC. The study will explore the diagnostic methods for EGFR mutations, clinical outcomes based on treatment modalities, and metastatic patterns in EGFR-mutated NSCLC patients. Moreover, it will investigate various aspects, including the safety and efficacy of a new third-generation EGFR tyrosine kinase inhibitor (TKI), lazertinib, approved for both first- and second-line treatments.</p><p><strong>Discussion: </strong>This study is expected to provide valuable insights into the epidemiology, risk factors, progression, and treatment outcomes of EGFR-mutated NSCLC in Korea. The Korean EGFR Registry will contribute significantly to the understanding of the complex dynamics of EGFR-mutated NSCLC, aiding in the development of more effective and personalized treatment strategies.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 1","pages":"e70043"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Insights on Continuous Renal Replacement Therapy for Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.","authors":"Siyao Zeng, Shanpeng Cui, Yue Li, Zhipeng Yao, Yunlong Li, Yang Cao, Lianghe Wen, Ming Li, Junbo Zheng, Hongliang Wang","doi":"10.1111/crj.70045","DOIUrl":"10.1111/crj.70045","url":null,"abstract":"<p><strong>Background: </strong>In recent times, the applications of continuous renal replacement therapy (CRRT) beyond kidney-related conditions have been progressively increasing, and its implementation in randomized controlled trials (RCTs) specifically for acute respiratory distress syndrome (ARDS) has been documented. This meta-analysis compiles all existing RCTs to assess whether CRRT benefits ARDS.</p><p><strong>Methods: </strong>We searched 12 databases in English and Chinese and two clinical trial centers up to November 28, 2023. The main outcome indicator is the mortality rate. Secondary outcome indicators include incidence of ventilator-associated pneumonia (VAP), ICU length of stay, mechanical ventilation time, oxygenation index (OI) at 24 h (h), OI at 48 h, OI at 72 h, OI at 7 days (d), partial pressure of oxygen (PaO₂) at 72 h, Acute Physiology and Chronic Health Evaluation II (APACHE II) score at 24 h, APACHE II score at 48 h, APACHE II score at 72 h, APACHE II score at 7 d, extravascular lung water indexes (EVLWI) at 72 h, TNF-α at 24 h, TNF-α at 7 d, IL-6 at 24 h, IL-6 at 48 h, IL-6 at 72 h, and IL-6 at 7 d. Statistical measures utilized include risk ratios (RR), weighted mean difference (WMD), and 95% confidence intervals (95% CI).</p><p><strong>Results: </strong>We summarized 36 studies, including 2123 patients. It was found that for ARDS, using CRRT in addition to conventional therapy can reduce the mortality rate (I² = 0%; RR: 0.40; 95% CI: 0.30-0.53; p < 0.01), the incidence of VAP (I² = 0%; RR: 0.44; 95% CI: 0.33-0.59; p < 0.01), ICU length of stay, mechanical ventilation time, and EVLWI at 72 h, as well as APACHE II score, TNF-α, and IL-6 at various time points. Additionally, it can increase OI during different time intervals and PaO₂ at 72 h.</p><p><strong>Conclusions: </strong>Low-quality evidence suggests that compared with conventional therapy alone, the use of CRRT may be associated with a lower mortality rate, the incidence of VAP, ICU length of stay, mechanical ventilation time, EVLWI, APACHE II score, TNF-α, and IL-6 and may be related to better respiratory function. CRRT may be beneficial for ARDS patients. Future multicenter, well-designed, high-quality RCTs are needed to substantiate these findings.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 1","pages":"e70045"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explainable Machine Learning Predictions for the Benefit From Chemotherapy in Advanced Non-Small Cell Lung Cancer Without Available Targeted Mutations","authors":"Zhao Shuang,&nbsp;Xiong Xingyu,&nbsp;Cheng Yue,&nbsp;Yu Mingjing","doi":"10.1111/crj.70044","DOIUrl":"10.1111/crj.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Non-small cell lung cancer (NSCLC) is a global health challenge. Chemotherapy remains the standard therapy for advanced NSCLC without mutations, but drug resistance often reduces effectiveness. Developing more effective methods to predict and monitor chemotherapy benefits early is crucial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We carried out a retrospective cohort study of NSCLC patients without targeted mutations who received chemotherapy at West China Hospital from 2009 to 2013. We identified variables associated with chemotherapy outcomes and built four predictive models by machine learning. Shapley additive explanations (SHAP) interpreted the best model's predictions. The Kaplan–Meier method assessed key variables' impact on 5-year overall survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study enrolled 461 NSCLC patients. Eight variables were selected for the model: differentiation, surgery history, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), total bilirubin (TBIL), total protein (TP), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH). The extreme gradient boosting (Xgboost) model exhibited superior discriminatory ability in predicting complete response (CR) probabilities to chemotherapy, with an AUC of 0.78. SHAP plots showed surgery history and high differentiation were related to CR benefits from chemotherapy. Absence of surgery, higher NLR, higher PLR, and higher LDH were all independent prognostic factors for poor survivals in NSCLC patients without mutations receiving chemotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>By machine learning, we developed a predictive model to assess chemotherapy benefits in NSCLC patients without targeted mutations, utilizing eight readily available and non-invasive clinical indicators. Demonstrating satisfactory predictive performance and clinical practicability, this model may help clinicians identify patients' tendency to benefit from chemotherapy, potentially improving their prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concomitant ALK Fusion and TP53/EGFR Mutation Lead to Adverse Prognostic Outcome","authors":"Mingyuan Du,&nbsp;Cuiwei Liu,&nbsp;Leichong Chen,&nbsp;Zhenyu Li,&nbsp;Sijia Zhang,&nbsp;Rui Meng","doi":"10.1111/crj.70041","DOIUrl":"10.1111/crj.70041","url":null,"abstract":"<p>Lung cancer treatment has evolved at the molecular level. Detecting the presence of driver genes in lung cancer fundamentally alters the choice of therapeutic regimens and the outcome of this disease. ALK fusion mutation is one of the most important mutations in nonsmall cell lung cancer (NSCLC). Also, it often has other coexisting mutation types. TP53 is the most common coexisting mutation type, whereas the EGFR/ALK coexisting mutation type is extremely rare. There is still no definite conclusion about the impact of the multimutation and best treatment options for NSCLC patients with advanced multimutation. In this study, we report three cases of NSCLC with ALK fusion mutations as well as ALK combined with TP53 mutations and ALK combined with EGFR mutations. Combining cases from our oncology center and previous literature, we found that NSCLC patients with coexisting ALK fusion mutations and other mutations have poorer response to targeted therapy and poorer prognosis, and we also compared the efficacy rates of various types of coexisting mutations for different treatment regimens. Therefore, this review can help to evaluate the prognosis of NSCLC patients with coexisting mutations and the efficacy of targeted therapies and to find more favorable treatment options for patients with this type of coexisting mutations.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dramatic Response to Ensartinib in Metastatic Neuroendocrine Tumors With a Novel CEP44-ALK Fusion: A Case Report and Literature Review","authors":"Haiyang Chen,&nbsp;Yingxi Wu,&nbsp;Xuan Wu,&nbsp;Kai Wang,&nbsp;Qingxin Xia,&nbsp;Qiming Wang","doi":"10.1111/crj.70040","DOIUrl":"10.1111/crj.70040","url":null,"abstract":"<p>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.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Association Between Monounsaturated Fatty Acids and Lung Cancer: A Two-Sample Mendelian Randomization Study","authors":"Shaofeng Zhang,&nbsp;Jia Jiang,&nbsp;Xiping Wu,&nbsp;Jiayi Liu,&nbsp;Wei Lei,&nbsp;Siqin Chen,&nbsp;Yaling Zeng,&nbsp;Xiang Liu,&nbsp;Qiang Xiao","doi":"10.1111/crj.70038","DOIUrl":"10.1111/crj.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to investigate the potential causal relationship between monounsaturated fatty acids (MUFAs) and lung cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genetic data on MUFAs and pathological subtypes of lung cancer were extracted from genome-wide association studies (GWAS). The primary analysis utilized inverse-variance weighted analysis (IVW), with additional methods including the weighted median method, MR-Egger regression method, and weighted model method. Sensitivity analysis was conducted to assess the robustness of the findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The inverse variance–weighted (IVW) analysis of monounsaturated fatty acids in relation to lung adenocarcinoma yielded an odds ratio (OR) of 1.059 with a 95% confidence interval of 0.960 to 1.168 and a <i>p</i> value of 0.252. Similarly, for lung squamous cell carcinoma, the IVW analysis produced odd ratios of 0.884, 95% confidence intervals of 0.747 to 1.045, and a <i>p</i> value of 0.148. In the case of small cell lung cancer, the odds ratio was 0.936, the 95% confidence interval was 0.751 to 1.166, and the <i>p</i> value was 0.554.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>It can be concluded that there is no direct causal relationship between monounsaturated fatty acids and the development of lung cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Response to Penpulimab Combined With Anlotinib and Chemotherapy in a Thoracic SMARCA4-UT Without PD-L1 Expression: A Case Report and Review of Literature","authors":"Yuanhang Wang,&nbsp;Kelei Zhao,&nbsp;Jingjing Zhang,&nbsp;Xiaohan Yuan,&nbsp;Yanting Liu,&nbsp;Jinghang Zhang,&nbsp;Ping Lu,&nbsp;Min Zhang","doi":"10.1111/crj.70036","DOIUrl":"10.1111/crj.70036","url":null,"abstract":"<p>SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) in the chest is a high-grade malignant tumor that grows rapidly and often carries a poor prognosis. Unfortunately, there are currently no effective treatment available until now. Here, we report a case of SMARCA4-UT in a patient who showed a swift response to a combination treatment of penpulimab, anlotinib, and chemotherapy. A 55-year-old man was diagnosed with thoracic SMARCA4-UT along with metastases to multiple lymph nodes, the pleura, and bones. Immunohistochemical (IHC) testing indicated the absence of PD-L1 expression in tumor cells. He was given sintilimab and anlotinib as first line treatment. However, a follow-up chest CT revealed progressive disease (PD) after the first cycle treatment. Subsequently, the second line regimen was modified to etoposide and cisplatin (EP) combined with anlotinib and penpulimab. The effectiveness evaluation revealed partial remission (PR) following two cycles of the second-line regimen treatment. Notably, the patient's progress-free survival (PFS) exceeds 7 months and the overall survival up to 12 months. Our case implies that a combination of chemotherapy, anlotinib, and penpulimab might offer a promising therapeutic approach for PD-L1-negative thoracic SMARCA4-UT.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revolutionizing NSCLC Treatment: Immunotherapy Strategies for EGFR-TKIs Resistance","authors":"Jin Tian,&nbsp;Zhiqi Shi,&nbsp;Lili Zhao,&nbsp;Peng Liu,&nbsp;Xiaojun Sun,&nbsp;Lin Long,&nbsp;Jianhua Zang,&nbsp;Jun Xiao","doi":"10.1111/crj.70037","DOIUrl":"10.1111/crj.70037","url":null,"abstract":"<p>Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard treatment choice for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations. EGFR-TKIs have made significant progress in the treatment of advanced NSCLC patients, but drug resistance issues still inevitably arise. The mechanism of drug resistance and subsequent treatment has been current research challenge and priority. Immune checkpoint inhibitors (ICIs) are a new choice for late-stage NSCLC patients without druggable molecular alterations. Currently, several studies have applied ICIs therapy for NSCLC patients with EGFR-TKIs resistance and explored the potential efficacy of ICIs. This review elaborates on the current status of immunotherapy after EGFR-TKIs resistance, including ICIs monotherapy, combined with EGFR-TKIs, chemotherapy, antiangiogenic drugs, and other therapies.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting HLA-E in Lung Cancer: The Therapeutic Potential of IRF5-Engineered M1-Macrophage-Derived Exosomes","authors":"Xuqin Feng,&nbsp;Xiangyu Lai,&nbsp;Mingming Zhou,&nbsp;Jun Bie,&nbsp;Tingting Li,&nbsp;Dan Wang,&nbsp;Silin Chen,&nbsp;Xin Hu,&nbsp;Chunyu Wang,&nbsp;Peng Xu","doi":"10.1111/crj.70035","DOIUrl":"https://doi.org/10.1111/crj.70035","url":null,"abstract":"<p>Immunotherapy is a pivotal approach in the treatment of lung cancer. Although HLA-E is a potential target for tumor immunotherapy, its role in lung cancer remains unclear. Previous studies have identified the transcription factor IRF5 as a characteristic gene of M1-like macrophages, highlighting its crucial role in promoting antitumor immune responses. In this study, we developed an engineered M1-like macrophage exosomes expressing IRF5 (IRF5 M1-exos) and demonstrated their ability to inhibit proliferation, migration, and invasion of lung cancer cells. Moreover, our experiments using a nude mouse model revealed that IRF5 M1-exos exerted potent therapeutic effects by effectively suppressing tumor growth. Notably, the mechanism by which IRF5 exerts its antitumor function through HLA-E regulation in lung cancer has not been fully elucidated. Here, we identified HLA-E as a downstream target gene of IRF5 and demonstrated that the overexpression of HLA-E can counteract the tumor-promoting effects induced by si-IRF5 M1-exos. These results suggest that M1 macrophage-derived exosomes, enriched with the transcription factor IRF5, exhibit potent antitumor activity by up-regulating HLA-E in lung cancer cells. Therefore, IRF5 M1-exos represent an attractive therapeutic strategy for lung cancer.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver Function Biomarkers and Lung Cancer Risk: A Prospective Cohort Study in the UK Biobank.","authors":"Xiangyu Sun, Zeqin Guo, Yanpei Zhang, Zhuangzhuang Liu, Jingrong Xiong, Mingliang Cai, Jiale Tan, Yan Lin, Zihang Yu, Kunheng Du, Enli Lu, Xiaolin Xia","doi":"10.1111/crj.70042","DOIUrl":"10.1111/crj.70042","url":null,"abstract":"<p><strong>Background: </strong>As the primary organ of metabolism and detoxification, the liver may contribute to the pathogenesis of lung cancer. We aimed to illuminate the intricate link between liver function biomarkers and lung cancer risk, as well as delineate the role of smoking behavior within this association.</p><p><strong>Methods: </strong>We investigated the associations of seven liver function biomarkers levels (alkaline phosphatase [ALP], alanine transaminase [ALT], total bilirubin [TBIL], albumin [ALB], gamma-glutamyltransferase [GGT], aspartate transaminase [AST], and total protein [TP]) with lung cancer risk across the UK Biobank (N = 337 499) through restricted cubic splines and Cox proportional hazards models. Moreover, Mendelian randomization (MR) was utilized to evaluate the causal effect of smoking behavior on these biomarkers. Then a lung cancer risk prediction model was developed among smokers by backward stepwise logistic regression.</p><p><strong>Results: </strong>During a median follow-up of 13.3 years, 3003 lung cancer cases were identified. We found ALP levels positively associated with lung cancer risk, whereas ALT, TBIL, ALB, and AST were inversely correlated; TP exhibited a U-shaped association, whereas GGT displayed a mirrored J-shaped relationship. These associations were amplified among smokers. MR analysis indicated that smoking behavior could increase ALP (odds ratio [OR]: 1.05) and GGT (OR: 1.15) levels while decreasing TBIL (OR: 0.92), ALB (OR: 0.92), and TP (OR: 0.96) levels. The lung cancer risk model incorporating these biomarkers in smokers demonstrated robust discrimination.</p><p><strong>Conclusion: </strong>Our finding provides perspectives and evidences towards the intricate crosstalk between the hepatic and pulmonary systems, as well as the processes through which tobacco catalyzes lung carcinogenesis.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 12","pages":"e70042"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}