Thoracic Cancer最新文献

{"title":"Metastasis of Small Cell Lung Cancer to the External Auditory Canal: A Case Report.","authors":"Toshiyuki Ito, Masamichi Yoshida, Hiroto Miki, Hiroki Goto, Shuuji Kodama, Atsushi Fujiwara, Hajime Fujimoto, Tetsu Kobayashi","doi":"10.1111/1759-7714.70059","DOIUrl":"10.1111/1759-7714.70059","url":null,"abstract":"<p><p>Patients with lung cancer often develop distant metastases; however, metastasis to the external auditory canal is rare. We report the case of a 77-year-old man who presented with left-sided hearing loss, otalgia, and a red mass in the left external auditory canal. Computed tomography revealed masses in the left external auditory canal, lung, and pancreas. Histopathological analysis confirmed small cell lung cancer, with thyroid transcription factor 1 positivity in multiple lesions, suggesting a primary tumor in lung. Treatment with carboplatin and etoposide led to a reduction in metastatic lesions, including those in the external auditory canal, and improved hearing impairment. This case highlights a rare instance in which chemotherapy improved ear symptoms in a patient with small cell lung cancer metastasis to the external auditory. Written informed consent was obtained from the patient for the publication of this case report and accompanying images.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 7","pages":"e70059"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival and Perioperative Outcomes After Addition of Immunotherapy to Neoadjuvant Chemoradiotherapy for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma.","authors":"Canjun Li, Xin Wang, Lei Deng, Jianyang Wang, Tao Zhang, Wenqing Wang, Wenyang Liu, Jima Lv, Qinfu Feng, Zongmei Zhou, Xiankai Chen, Ruixiang Zhang, Jianjun Qin, Yin Li, Nan Bi","doi":"10.1111/1759-7714.70054","DOIUrl":"https://doi.org/10.1111/1759-7714.70054","url":null,"abstract":"<p><strong>Background: </strong>Currently, neoadjuvant chemoradiotherapy combined with immunotherapy (NCRI) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is attracting attention. The purpose of this study was to compare the surgical outcomes and survival between patients receiving NCRI and neoadjuvant chemoradiotherapy (NCRT) followed by surgery.</p><p><strong>Methods: </strong>This study retrospectively included patients with locally advanced ESCC and treated with NCRI or NCRT followed by esophagectomy. Two groups were compared for pathologic complete response (pCR) rate, R0 resection rate, and 3-year recurrence-free survival (RFS). Surgery time, the number of lymph nodes removed, postoperative complications, and 30-day mortality were also compared. Propensity score matching (PSM) was performed to minimize the potential impact of confounding factors.</p><p><strong>Results: </strong>After PSM, patients in the NCRI group showed a significantly higher pCR rate compared with those in the NCRT group (54.2% vs. 27.1%, p = 0.046). R0 resection rate (100% vs. 89.6%, p = 0.251), surgery time (p = 0.614), the number of lymph nodes removed (p = 0.526), the incidence of total postoperative complications (46.4% vs. 37.9%, p = 0.564) and 30-day mortality (3.6% vs. 1.1%, p = 0.983) were comparable between the two groups. The NCRI group exhibited a significantly higher 3-year RFS rate compared to the NCRT group (79.2% vs. 62.5%, p = 0.032).</p><p><strong>Conclusion: </strong>For patients with locally advanced ESCC, NCRI showed a significantly higher pCR rate than conventional NCRT, without increased operative risk. NCRI followed by surgery exhibited a superior RFS compared to NCRT followed by surgery. Prospective studies are needed in the future.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 7","pages":"e70054"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consolidation Chemotherapy Provided Survival Benefit for Esophageal Squamous Cell Carcinoma Patients Who Underwent Concurrent Chemoradiotherapy Lower Than 60 Gy.","authors":"Hualei Zhang, Qi Wang, Ping Wang, Bo Tang","doi":"10.1111/1759-7714.70012","DOIUrl":"10.1111/1759-7714.70012","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of consolidation chemotherapy (CCT) following concurrent chemoradiotherapy (CCRT) has not been clearly defined in esophageal squamous cell carcinoma (ESCC). This study determined which patients with stage II-IVA ESCC benefitted from CCT.</p><p><strong>Methods: </strong>351 patients with ESCC were retrospectively reviewed. 185 patients received CCRT alone and 166 received CCRT plus CCT. Subset analyses were conducted on all patients' characteristics. Factors associated with survival were analyzed using the Kaplan-Meier method and a Cox proportional hazards model. The Propensity score matching (PSM) technique was used to compensate for differences in patients' characteristics.</p><p><strong>Results: </strong>The median OS were 17.7 months and 38.4 months in the CCRT alone group and CCRT+CCT group (p = 0.002), respectively. Multivariable Cox regression analysis determined that CCT was associated with improved OS (p = 0.002, HR 0.592, 95% CI 0.423-0.829); After PSM, relative to the CCRT group, patients who received CCT experienced improved OS (17.7 months vs. 38.4 months, p = 0.0139). Subgroup analysis showed that CCT was more effective in radiation dose < 60 Gy (p = 0.002, HR 0.368, 95% CI 0.194-0.700). After matching between radiation dose, in the low dose cohort, the median OS was 13.2 months and 20.7 months in the CCRT alone group and CCRT+CCT group, respectively (p = 0.0028), the multivariate analysis results showed that CCT retained its statistical significance (p = 0.002, HR 0.353, 95% CI 0.183-0.681). In the high dose cohort, the median OS were 21.6 months and 23.6 months in the CCRT alone group and CCRT+CCT group, respectively (p = 0.5512).</p><p><strong>Conclusions: </strong>We recommend that CCT treatment should be considered for ESCC patients who underwent CCRT using < 60 Gy. Further studies are needed to confirm these results.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 7","pages":"e70012"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is It Safe to Omit Any Chest X-Ray Before Removing the Chest Drain After Elective, Non-Cardiac Thoracic Surgery? A Single-Center, Retrospective, Case-Control Study.","authors":"Ioannis Karampinis, Carolin Reker, Laura Grifone, Fabio Souschek, Christian Galata, Davor Stamenovic, Eric Roessner","doi":"10.1111/1759-7714.70050","DOIUrl":"10.1111/1759-7714.70050","url":null,"abstract":"<p><strong>Background: </strong>Every patient undergoing non-cardiac thoracic surgery will receive several chest X-rays through the perioperative period. The patient might receive a preoperative X-ray as a baseline as well as several X-rays before and after drain removal. This routine has several disadvantages, for the patient, the health care system and the medical staff. Purpose of this study was to examine if all X-rays before removal of the drain can be omitted.</p><p><strong>Methods: </strong>Two hundred fifty-five patients who underwent elective thoracic surgery were included in this retrospective analysis. Patients undergoing urgent procedures or empyema surgery, as well as patients with symptoms requiring further diagnostic measures or patients who required clamping of the drain before removal, were excluded.</p><p><strong>Results: </strong>Forty-five patients received an X-ray before removal of the drain, and 210 patients did not. The X-ray group developed significantly more minor complications than the no X-ray group. 46.7% of the X-rays before drain removal (X-ray group) were reported with abnormalities. However, these abnormalities never led to a change in patient care. Drainage time and postoperative hospital stay were significantly longer in the X-ray group.</p><p><strong>Conclusions: </strong>Omitting any X-ray between surgery and removal of the chest drain appears to be safe in our retrospective patient cohort. The proposed benefits of omitting the X-ray are very relevant for the health care system, the medical and nursing teams, and, more importantly, for the patients. Evidence suggests that X-ray of patients regularly do not exist. It is therefore reasonable to consider exploring this question in a formal prospective trial.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 7","pages":"e70050"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological Factors That Predict Different Responses of Breast and Axillary Tumors to Neoadjuvant Chemotherapy and Prognosis Among Patients With Node-Positive Breast Cancer: Real World Data.","authors":"Danyang Ji, Bo Lan, Jiayu Wang, Fei Ma, Yang Luo, Qing Li, Pin Zhang, Ruigang Cai, Qiao Li, Shanshan Chen, Binghe Xu, Ying Fan","doi":"10.1111/1759-7714.70035","DOIUrl":"10.1111/1759-7714.70035","url":null,"abstract":"<p><strong>Background: </strong>Pathological complete response (pCR) has been proven to be related to prognosis. pCR can be further classified as pCR of the breast (bpCR), pCR of axillary lymph nodes (apCR) or pCR of both tumors. The aim of this study was to elucidate the outcomes and clinicopathological characteristics associated with different patterns of pCR.</p><p><strong>Methods: </strong>Patients with node-positive disease who received neoadjuvant chemotherapy between August 2009 and July 2016 and who achieved pCR in axillary lymph nodes, breast or both were included. Multivariate logistic regression was used to identify factors related to different patterns of pCR.</p><p><strong>Results: </strong>Among the 271 patients who were included in the study, 42.1% achieved total pCR, 46.1% achieved ApCR, and 11.8% achieved BpCR. Disease-free survival (DFS) was significantly better in the total pCR group than in the limited pCR groups throughout the entire cohort (p = 0.042). Univariate and multivariate analyses indicated that patients with HR-negative disease and a high Ki-67 proliferation index were more likely to achieve total pCR. Patients with earlier T stage disease were more likely to achieve pCR only in the breast. Among patients who achieved limited pCR, there was no significant difference in terms of whether these patients received intensified adjuvant chemotherapy.</p><p><strong>Conclusions: </strong>Total pCR is still the best marker for predicting survival benefit in patients receiving neoadjuvant chemotherapy, and total pCR is more likely to be achieved in patients with HR-negative disease and a high Ki-67 proliferation index. T stage and N stage may predict apCR and bpCR, respectively.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 7","pages":"e70035"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-L1 Scoring Models for Non-Small Cell Lung Cancer in China: Current Status, AI-Assisted Solutions and Future Perspectives.","authors":"Ziling Huang, Shen Wang, Jiansong Zhou, Haiquan Chen, Yuan Li","doi":"10.1111/1759-7714.70042","DOIUrl":"10.1111/1759-7714.70042","url":null,"abstract":"<p><p>Immunotherapy has revolutionized the diagnosis and treatment model for patients with advanced non-small cell lung cancer (NSCLC). Numerous clinical trials and real-world reports have confirmed that PD-L1 status is a key factor for the successful use of immunotherapy in NSCLC, by predicting clinical outcomes and identifying patients most likely to benefit from this treatment. Therefore, accurate and standardized evaluation of PD-L1 expression is crucial. Currently, PD-L1 testing in China faces several challenges, including a heavy pathologist workload, a shortage of highly trained pathologists plus the inadequate capacity of diagnostic laboratories, confusion around different scoring methods, cut-off values, and indications, and limited concordance between PD-L1 assays. In this review, we summarize the current status and limitations of PD-L1 testing for patients with NSCLC in China and discuss recent progress in artificial intelligence-assisted PD-L1 scoring. Our review aims to support improvements in clinical PD-L1 testing practice and optimization of the prognosis and outcomes of immunotherapy in this patient population.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 7","pages":"e70042"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of TP53 Mutations and EGFR Amplification in Risk Stratification of Early-Stage EGFR-Mutated Non-Small Cell Lung Cancer With Immunohistochemistry as a Surrogate Marker.","authors":"Meejeong Kim, Gyeong Sin Park, Kyo Young Lee, Seok Whan Moon, Yeoun Eun Sung","doi":"10.1111/1759-7714.70058","DOIUrl":"10.1111/1759-7714.70058","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer-related mortality, with recurrence risks posing significant challenges in early-stage disease management. While epidermal growth factor receptor (EGFR) mutations are common, the role of concurrent genetic alterations remains underexplored, and findings have often been inconsistent, particularly in early-stage tumors.</p><p><strong>Methods: </strong>We retrospectively analyzed 424 EGFR-mutated NSCLC patients diagnosed from 2017 to 2022. Next-generation sequencing (NGS) was used to identify genetic alterations, and immunohistochemistry (IHC) was employed to correlate TP53 mutations and EGFR amplification with protein expression. Survival outcomes were assessed using Kaplan-Meier and Cox regression analyses, while predictive cutoffs were determined with receiver operating characteristic (ROC) curve analysis.</p><p><strong>Results: </strong>TP53 mutations and EGFR amplification were more prevalent in Stages 2-4 compared to Stage 1 (p < 0.001 and 0.005, respectively). In Stage 1, TP53 mutations, particularly exon 4 and frameshift/nonsense types, were associated with worse overall survival (OS) and disease-free survival (DFS). EGFR amplification was linked to shorter DFS in Stage 1 (p = 0.006). Both alterations correlated with aggressive pathological features, including advanced N stage, lymphovascular invasion, and high histological grade. IHC cutoffs of 15% for TP53 and H-score ≥ 180 for EGFR amplification demonstrated high predictive accuracy (AUC = 0.981 and 0.936, respectively).</p><p><strong>Conclusion: </strong>Specific subtypes of TP53 mutations and EGFR amplification are important prognostic markers in early-stage NSCLC. IHC offers a practical surrogate for genetic testing, aiding in risk stratification and guiding adjuvant therapy decisions for high-risk patients. Larger validation studies are warranted.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 7","pages":"e70058"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytoplasmic HuR Expression Enhances Chemoresistance in Pleural Mesothelioma Through Increased Expression of CALB2, Promotion of the E2F Pathway, and Suppression of the p53 Pathway.","authors":"Susumu Kirimura, Morito Kurata, Hironori Ishibashi, Yusuke Taniguchi, Yuko Kinowaki, Keisuke Sugita, Kenichi Okubo","doi":"10.1111/1759-7714.70062","DOIUrl":"https://doi.org/10.1111/1759-7714.70062","url":null,"abstract":"<p><strong>Introduction: </strong>Chemotherapy is crucial for treating pleural mesothelioma; however, the outcomes are poor, necessitating an urgent need to study the mechanism of chemotherapy resistance in mesothelioma cells. Human antigen R (HuR), an RNA-binding protein and key post-transcriptional regulator of mRNA, is linked to poor prognosis in cancers like mesothelioma. We investigated the involvement of cytoplasmic HuR expression in drug resistance mechanisms in mesothelioma.</p><p><strong>Methods: </strong>We retrospectively evaluated cytoplasmic HuR expression in 30 patients with pleural mesothelioma who underwent surgical resection using immunohistochemistry. We also examined the role of forced cytoplasmic expression of HuR in drug resistance using mesothelioma cell lines and performed RNA-Seq analysis to identify gene expression changes responsible for drug resistance acquisition via HuR cytoplasmic expression.</p><p><strong>Results: </strong>Patients with mesotheliomas who expressed cytoplasmic HuR exhibited significantly worse disease-free survival following post-operative chemotherapy. Forced cytoplasmic HuR expression in mesothelioma cell lines increased chemotherapy resistance through increased expression of CALB2, upregulation of the E2F pathway and suppression of the p53 pathway.</p><p><strong>Conclusions: </strong>Cytoplasmic HuR expression increases the chemoresistance and postoperative recurrence risk of pleural mesothelioma, making it a potential biomarker for predicting therapeutic prognosis. However, the mechanism of HuR transfer to the cytoplasm remains unclear for therapeutic application.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 7","pages":"e70062"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFI30 Knockdown Inhibits ESCC Progression by Promoting Apoptosis and Senescence via Activation of JNK and P21/P16 Pathways.","authors":"Wenyao Xie, Sisi Wei, Caiting Feng, Yuhui Fu, Zhe Zhang, Suli Dai, Cong Zhang, Lianmei Zhao, Baoen Shan","doi":"10.1111/1759-7714.70063","DOIUrl":"10.1111/1759-7714.70063","url":null,"abstract":"<p><strong>Background: </strong>Esophageal squamous cell carcinoma (ESCC) is a prevalent and deadly cancer, making it essential to understand the molecular mechanisms influencing its development and prognosis. The role of interferon-gamma-inducible protein 30 (IFI30) in antigen processing is well-established, but its impact on the progression of ESCC remains unclear. This study aimed to investigate the biological function and potential mechanisms of IFI30 in ESCC progression.</p><p><strong>Methods: </strong>Public databases, proteomics, and immunohistochemistry (IHC) were employed to analyze IFI30 expression. Cell proliferation, migration, and invasion were evaluated using MTS, colony formation, wound healing, and transwell assays. Nude mouse xenograft models were established to assess the effects of IFI30 knockdown in vivo. Quantitative proteomics was utilized to identify differentially expressed proteins (DEPs) and pathways altered by IFI30 knockdown. Cell apoptosis and senescence were evaluated by flow cytometry, SA-β-gal staining, and reactive oxygen species (ROS) analysis.</p><p><strong>Results: </strong>IFI30 was highly expressed in ESCC and was correlated with advanced stage and poor prognosis. IFI30 knockdown inhibited ESCC cell proliferation, migration, and invasion in vitro and suppressed tumor growth in vivo. DEPs were mainly enriched in biological pathways related to apoptosis, mitophagy, cellular senescence, and lysosome. Furthermore, IFI30 knockdown in ESCC cells upregulated HRAS expression, increased ROS production, activated the JNK signaling pathway, and elevated the expression of P16 and P21, thereby promoting apoptosis and senescence.</p><p><strong>Conclusions: </strong>This study suggests that IFI30 may regulate the JNK and P21/P16 pathways, exerting pro-tumorigenic effects in ESCC. IFI30 could serve as a potential novel target for ESCC treatment.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 7","pages":"e70063"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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