Clinical Respiratory Journal最新文献

{"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":"A Nomogram for Predicting Recurrence in Stage I Non-Small Cell Lung Cancer","authors":"Rongrong Bian,&nbsp;Feng Zhao,&nbsp;Bo Peng,&nbsp;Jin Zhang,&nbsp;Qixing Mao,&nbsp;Lin Wang,&nbsp;Qiang Chen","doi":"10.1111/crj.70022","DOIUrl":"https://doi.org/10.1111/crj.70022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Early-stage non–small cell lung cancer (NSCLC) is being diagnosed increasingly, and in 30% of diagnosed patients, recurrence will develop within 5 years. Thus, it is urgent to identify recurrence-related markers to optimize the management of patient-tailored therapeutics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The eligible datasets were downloaded from TCGA and GEO. In the discovery phase, two algorithms, least absolute shrinkage and selector operation and support vector machine-recursive feature elimination, were used to identify candidate genes. The recurrence-associated signature was developed by penalized Cox regression. The nomogram was constructed and further tested via other independent cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this retrospective study, 14 eligible datasets and 7 published signatures were included. A 13-gene based signature was generated by penalized Cox regression categorized training cohort into high-risk and low-risk subgroups (HR = 8.873, 95% CI: 4.228–18.480 <i>p</i> &lt; 0.001). Furthermore, a nomogram integrating the recurrence-related signature, age, and histology was developed to predict the recurrence-free survival in the training cohort, which performed well in the two external validation cohorts (concordance index: 0.737, 95% CI: 0.732–0.742, <i>p</i> &lt; 0.001; 0.666, 95% CI: 0.650–0.682, <i>p</i> &lt; 0.001; 0.651, 95% CI: 0.637–0.665, <i>p</i> &lt; 0.001, respectively). The nomogram was further performed well in the Jiangsu cohort enrolled 163 patients (HR = 2.723, 95% CI: 1.526–4.859, <i>p</i> = 0.001). Post-operative adjuvant therapy achieved evaluated disease-free survival in high and intermediate risk groups (HR = 4.791, 95% CI: 1.081–21.231, <i>p</i> = 0.039).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The proposed nomogram is a promising tool for estimating recurrence-free survival in stage I NSCLC, which might have tremendous value in management of early stage NSCLC and guiding adjuvant therapy strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142707982","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":"Highly Sensitive and Specific Panels of Plasma Exosomal microRNAs for Identification of Malignant Pulmonary Nodules","authors":"Rui Tao,&nbsp;Dandan Wang,&nbsp;Wenjing Pei,&nbsp;Yanfei Liu,&nbsp;Pengcheng Liu,&nbsp;Renming Li,&nbsp;Jiegou Xu,&nbsp;Jing Ye,&nbsp;Dahai Zhao","doi":"10.1111/crj.70034","DOIUrl":"10.1111/crj.70034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>With wide application of computed tomography (CT) in early lung cancer screening, solitary pulmonary nodules (SPNs) are frequently detected. Due to their high etiological diversity and potential for malignancy, rapid and accurate identification and malignant SPNs are crucial in the clinical management. In the present study, plasma exosomal microRNAs were identified and evaluated as sensitive and specific indicators for malignant SPNs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Exosomal miRNAs isolated from the plasmas of pathologically confirmed patients with SPN (four malignant and four benign, designated as the screening set) were subjected for high throughput sequencing and eight candidate miRNAs were selected. The pre-operation plasma levels of the candidate miRNAs in 77 patients with SPN (48 malignant and 29 benign, designated as the identification set) were detected by quantitative PCR, five miRNAs were identified as potential biomarkers for malignant SPNs, and the diagnostic values of the five miRNAs each alone or combined were then analyzed by AUROC analysis. The prediction values of the identified miRNAs were further evaluated in 95 patients with SPN (double blind, 74 malignant and 21 benign, designated as the validation set).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High-throughput sequencing identified 45 miRNAs with statistical differences between benign and malignant SPNs. Among the eight candidate miRNAs in the identification set, miR-1-3p alone had the best diagnostic value, with the sensitivities and specificities of 89.6% and 100% for malignant SPNs. Unexpectedly, when miR-1-3p was combined with miR-99a-5p, both the sensitivity and specificity reached 100% for malignant SPNs. miR-1-3p+miR-125b-5p and miR-1-3p+miR-218-5p were also good indicators of malignant SPNs with sensitivities of 95.8% and 97.9%, specificities of 100% and 96.6%. Further analysis of these microRNA combinations in the validation set indicated that the PPV were 91.4%, 97.4%, and 93.5% and the NPV were 100%, 100%, and 88.9% for miR-1-3p+miR-99a-5p, miR-1-3p+miR-218-5p, and miR-1-3p+miR-125b-5p, with the sensitivities were 100%, 100%, and 97.3% and the specificities were 66.7%, 90.5%, and 76.2% for miR-1-3p+miR-99a-5p, miR-1-3p+miR-218-5p, and miR-1-3p+miR-125b-5p, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Through high throughput sequencing, qPCR determination of plasma microRNAs and AUROC analysis, miR-1-3p combined with miR-99a-5p, miR-125b-5p, or miR-218-5p have been found to be ","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645232","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":"A Novel Scale for Diagnosis of Pulmonary Ground-Glass Nodules: A Multicenter and Ambispective Cohort Study","authors":"Minhao Yu,&nbsp;Yalin Cheng,&nbsp;Tao Wen,&nbsp;Liming Zhang,&nbsp;Xiubo Wei,&nbsp;Yonghong Wang,&nbsp;Jiang Du,&nbsp;GuangKe Xie,&nbsp;Lei Bi","doi":"10.1111/crj.70027","DOIUrl":"10.1111/crj.70027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A screening tool was devised to aid the diagnosis and treatment of ground-glass nodules (GGNs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The current ambispective cohort study included retrospective collation of 20 variables synthesizing a patient's clinical characteristics, serum tumor markers, and CT results, which allowed division into noninvasive (benign, atypical adenomatous hyperplasia, and adenocarcinoma in situ) and invasive (minimally invasive and invasive adenocarcinomas) tumors to build a prediction nomogram and GGN screening scale. The model was verified internally. A prospective cohort of patients was randomly divided by envelope method into those assessed by the GGN screening scale and those assessed via CT values. The diagnostic efficiencies were compared to allow external verification of the model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>A total of 223 patients with 225 GGNs were recruited into the retrospective cohort between January 2021 and December 2022. Multivariable analysis showed sex, diameter, air bronchogram, and vessel convergence sign to be independent factors for prediction of noninvasive and invasive GGNs. Internal verification showed the model had a sensitivity of 70.7% and specificity of 75.0% with the Youden index at 0.457 and area under the curve (AUC) of 0.793 (95% CI: 0.734–0.852). Calibration curves indicated good internal stability (<i>p</i> = 0.357). Between January 2023 and March 2023, 147 patients with 148 GGNs were recruited into the prospective cohort. External verification showed the model had a sensitivity of 92.4% and specificity of 40.0% with the Youden index at 0.324 and AUC of 0.678 (95% CI: 0.509–0.847). Calibration curves indicated good external stability (<i>p</i> = 0.088). The scale was shown to have a sensitivity of 75.00%, specificity of 37.50%, positive predictive value of 91.53%, negative predictive value of 14.29%, and accuracy of 71.25%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The GGN screening scale has high sensitivity and accuracy, making it suitable for diagnosis of GGNs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633056","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":"Prognostic Nomogram for Predicting Survival in Asian Patients With Small-Cell Lung Cancer: A Comprehensive Population-Based Study and External Verification","authors":"Yuanli Xia,&nbsp;Jingjing Qu,&nbsp;Yufang Wang,&nbsp;Yanping Zhu,&nbsp;Jianying Zhou,&nbsp;Jianya Zhou","doi":"10.1111/crj.70021","DOIUrl":"10.1111/crj.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The incidence of small cell lung cancer (SCLC) among Asian patients is on the rise. Nevertheless, there remains a deficiency in precise prognostic models tailored to the specific needs of this patient population. It is imperative to develop a novel nomogram aimed at forecasting the prognosis of Asian SCLC patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The SEER database supplied data on 661 Asian SCLC patients, who were then divided into training and internal validation sets through a random selection process. In addition, we identified 212 patients from a Chinese medical institution for the purpose of creating an external validation cohort. To forecast survival, we employed both univariate and multivariate analyses. The performance of our nomogram was assessed through calibration plots, the concordance index (C-index), and decision curve analysis (DCA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five independent prognostic factors were determined and integrated into the nomogram. C-index values for the training and internal validation cohorts were 0.774 (95% confidence interval [CI] = 0.751–0.797) and 0.731 (95%CI = 0.690–0.772), respectively. In the external validation cohort, the C-index is 0.712 (95% CI = 0.655–0.7692). Calibration curves demonstrated highly accurate predictions. When compared to the AJCC staging system, our model exhibited improved net benefits in DCA. Furthermore, the risk stratification system effectively differentiated patients with varying survival risks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We have created a novel nomogram for predicting the survival of Asian patients with SCLC. This nomogram has been subjected to external validation and has shown its superiority over the conventional TNM staging system. It offers a more precise and reliable means of forecasting the prognosis of Asian SCLC patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633066","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":"Ergotamine Targets KIF5A to Facilitate Anoikis in Lung Adenocarcinoma","authors":"Bin Bao,&nbsp;Xiaojun Yu,&nbsp;Wujun Zheng,&nbsp;Jiewei Sun","doi":"10.1111/crj.70020","DOIUrl":"10.1111/crj.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Kinesin family member 5A (KIF5A) has been reported to be closely related to cancer progression. The aim of this study was to investigate the effect of KIF5A on lung adenocarcinoma (LUAD) and its potential molecular mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using bioinformatics analysis methods and molecular experiments, the expression of KIF5A in LUAD was analyzed, with its expression in attached and detached tumor cells assessed. Gene set enrichment analysis (GSEA) of KIF5A was carried out. The small molecular drug with the highest affinity for KIF5A was screened out through molecular docking experiments, which was validated through cellular thermal shift assay (CETSA). Quantitative polymerase chain reaction (qPCR) was employed to measure the expression levels of anoikis-repressing genes (BCL2, CAV1), as well as anoikis-inducing gene (PDCD4). CCK-8 assay was applied to examine cell viability. Cell colony formation experiments were utilized to evaluate cell proliferation ability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed that KIF5A was highly upregulated in LUAD tissues and cells, with a higher level detected in detached LUAD cells. By resorting to bioinformatics analysis, we discovered that KIF5A was abundant in the anoikis pathway. Knocking down KIF5A reinforced anoikis in LUAD. Further screening identified Ergotamine as the small molecular drug with the highest affinity for KIF5A. The CETSA confirmed the binding relationship between the two. In addition, Ergotamine has a promoting effect on the anoikis of LUAD, while overexpression of KIF5A reversed the effects of Ergotamine on LUAD cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This project uncovered that the small molecular drug Ergotamine targets and inhibits the expression of KIF5A. Downregulated KIF5A can enhance the anoikis of LUAD. Our results supported the inhibition of KIF5A as an attractive therapeutic strategy for LUAD. This finding provides a new innovative pathway for the treatment of LUAD and offers a strong theoretical basis for the development of therapeutic drugs targeting KIF5A.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633062","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}