Clinical & Translational Oncology最新文献

{"title":"Exploring the efficacy and safety of laser interstitial thermal therapy for recurrent high-grade glioma: the first prospective cohort in China.","authors":"Yihe Wang, Sichang Chen, Jianwei Shi, Ting Tang, Yang Dai, Jinkun Xu, Penghu Wei, Xiaotong Fan, Jie Lu, Yongzhi Shan, Guoguang Zhao","doi":"10.1007/s12094-024-03779-9","DOIUrl":"10.1007/s12094-024-03779-9","url":null,"abstract":"<p><strong>Objective: </strong>Recurrent high-grade gliomas are complicated cancers that require additional treatment options. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a safe method for treating recurrent high-grade glioma; however, its use in China has not been reported. In this study, we aimed to investigate the safety and efficacy of an MRgLITT system (SinoVision™) developed in China for treating recurrent high-grade glioma.</p><p><strong>Methods: </strong>We included a prospective cohort of patients with recurrent high-grade glioma treated with the Chinese MRgLITT system between March 2021 and December 2022. Clinical data, including basic information, complication rates, outcomes, and survival analyses, were collected for patients who had at least 12 months of follow-up.</p><p><strong>Results: </strong>32 patients who completed a rountine follow-up period were enrolled. The estimated 1-year overall survival rate was 65.63%, including 56.52% and 88.89% patients with World Health Organization Grades IV and III gliomas, respectively. Baseline Karnofsky Performance Scale score, tumor grade and volume, and post-LITT chemo- and or radiotherapy were positive factors associated with MRgLITT for recurrent high-grade glioma outcomes. The overall complication rate was 9.38%.</p><p><strong>Conclusion: </strong>The Chinese MRgLITT system is a safe and effective treatment option for recurrent high-grade glioma. As it is a minimally invasive treatment approach that can be tailored to the individual's anatomy and physiology, MRg LITT may offer a viable alternative for patients who are not suitable candidates for conventional surgical resection.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2620-2628"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696023","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":"Optimizing genetic testing strategy for suspected attenuated adenomatous polyposis: effective solutions in public health systems.","authors":"Natalia García-Simón, Fátima Valentín, Ana Royuela, Beatriz Hidalgo-Calero, Ricardo Blázquez-Martín, Montserrat de-Miguel-Reyes, José María Sánchez-Zapardiel, Luisa Adán-Merino, Alejandro Rodríguez-Festa, Patricia Gallego-Gil, Pilar Mediavilla-Medel, Laura Quiñonero-Moreno, Lourdes Gutiérrez, Alberto Herreros-de-Tejada, Antonio Sánchez, Mariano Provencio, Atocha Romero","doi":"10.1007/s12094-024-03811-y","DOIUrl":"10.1007/s12094-024-03811-y","url":null,"abstract":"<p><strong>Background: </strong>APC and MUTYH genes are key in hereditary attenuated adenomatous polyposis syndromes. Guidelines recommend genetic testing based on polyp count, often overlooking age despite its impact on polyp prevalence.</p><p><strong>Aim: </strong>To enhance genetic testing strategies for suspected attenuated adenomatous polyposis by combining polyp count and age in a probability calculator.</p><p><strong>Methods: </strong>Retrospective study of adult patients referred to NGS genetic testing for suspected attenuated adenomatous polyposis (accumulated history of < 100 adenomas) (discovery cohort, N = 138). Data included age, adenoma count, and test results. A multivariable logistic regression model was developed to associate positive genetic test results with age and adenoma count. The model was externally validated with 259 patients from two tertiary hospitals in our region (validation cohort, N = 259).</p><p><strong>Results: </strong>In the discovery cohort, 13 (9.4%) patients had pathogenic mutations, being younger (OR:0.91, 95%CI 0.86-0.96) and having more adenomas (OR:1.08, 95%CI 1.04-1.13) compared to negative cases. The logistic regression model combining age and polyp count demonstrated an AUC of 0.92. Using a cutoff probability of 3.5%, the model achieved 100% sensitivity and 58% specificity in identifying positive cases. In the external validation, the model accurately predicted 14 out of 16 positive cases (88%). The remaining two positive cases were a patient with an AXIN2 mutation in heterozygosis, and a patient with a NTHL1 mutation in homozygosis. Performance evaluation of both hospitals yielded AUC values of 0.77 and 0.90.</p><p><strong>Conclusions: </strong>Older individuals with fewer polyps are less likely have hereditary syndromes. Including age in genetic testing criteria can enhance patient selection and cost-effectiveness.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2710-2718"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808574","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":"Rotenone adaptation promotes migration and invasion of p53-wild-type colon cancer through lipid metabolism.","authors":"Yingying Shi, Zhen Cao, Ling Ge, Lin Lei, Dan Tao, Juan Zhong, Dan Xu, Tao Geng, Xuetao Li, Ziwei Li, Shuaishuai Xing, Xinyu Wu, Zhongxu Wang, Linjun Li","doi":"10.1007/s12094-024-03785-x","DOIUrl":"10.1007/s12094-024-03785-x","url":null,"abstract":"<p><strong>Background: </strong>The association between mitochondrial dysfunction and multiple metabolic adaptations is increasingly being proven. We previously elucidated that mitochondrial complex I deficiency can promote glycolysis in mut-p53 SW480 cells. However, studies have revealed a phenotype with attenuated glycolysis but enhanced fatty acid oxidation (FAO) in invasive tumors. The interplay between complex I and FAO in carcinogenesis remains obscure.</p><p><strong>Methods: </strong>The p53 wild-type RKO cells were exposed to rotenone over at least 2 months to acquire rotenone adaptation cells. Then the transwell invasion assays and expression of metabolic enzymes were first detected in rotenone adaptation cells to illustrate whether rotenone adaptation is correlated with the invasion and FAO. The levels of epithelial-to-mesenchymal transition (EMT)-related proteins and acetyl-CoA in rotenone adaptation cells treated with etomoxir (ETO) and acetate were evaluated to verify the role of CPT1A in regulating invasion. Finally, the levels of reactive oxygen species (ROS) were detected. Meanwhile, the invasiveness and histone acetylation levels of rotenone adaptation cells were observed after adding an ROS inhibitor (N-acetyl-L-cysteine NAC) to demonstrate the molecular connection between FAO and invasion during rotenone adaptation.</p><p><strong>Results: </strong>We found long-term exposure to rotenone (a mitochondrial complex I inhibitor) led to EMT and high CPT1A expression in wt-p53 colon cancer. The inhibition of CPT1A suppressed the invasion and reduced histone acetylation, which was rescued by supplementing with acetate. Mechanistically, ROS is crucial for lipid metabolism remodeling.</p><p><strong>Conclusion: </strong>Our study provides a novel understanding of the role of complex I in lipid reprogramming facilitating colon cancer invasion and metastasis.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2557-2567"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752102","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":"XRCC1 is linked to poor prognosis in adenocarcinoma of the esophagogastric junction after radiotherapy: transcriptome and alternative splicing events analysis.","authors":"Pengfei Lu, Min Xia, Juan Li, Hongzhi Qi, Hui Wang, Rui Mao","doi":"10.1007/s12094-024-03773-1","DOIUrl":"10.1007/s12094-024-03773-1","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to (i) investigate the relationship between X-ray repair cross-complementing protein 1 gene (XRCC1) and prognosis in patients with adenocarcinoma of the esophagogastric junction (AEG), and (ii) analyze the roles of XRCC1 in human gastric adenocarcinoma (AGS) cells following X-ray radiation.</p><p><strong>Methods: </strong>A total of 46 AEG patients were enrolled and examined for XRCC1 protein by immunohistochemistry. XRCC1 was knocked down in AGS cells by transfection, and AGS cells were subsequently exposed to 6 Gy of X-ray radiation. XRCC1 mRNA and protein expression was examined via quantitative real-time PCR (qRT-PCR) and Western blot analysis. The apoptosis of AGS cells was examined by flow cytometer. RNA-sequencing technology was used to identified differentially expressed genes and alternative splicing events following XRCC1 knockdown and radiation exposure.</p><p><strong>Results: </strong>XRCC1 positivity was strongly associated with distant metastasis, pathological tumor-node-metastasis (pTNM) classification, and radiotherapy resistance in AEG patients. A significant difference in progression-free survival was observed between AEG patients with low and high XRCC1 protein expression. The knockdown of XRCC1 notably exacerbated the effects of X-ray radiation on apoptosis in AGS cells. Additionally, X-ray radiation modified the expression of genes related to apoptosis and immune response in XRCC1-knockdown AGS cells. Furthermore, the generation of splice variants was influenced by XRCC1 knockdown in AGS cells.</p><p><strong>Conclusion: </strong>XRCC1 may serve as a key oncogene that elucidates the role of alternative splicing events in the progression of AEG following X-ray treatment.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2502-2516"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631903","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":"Association of hTERT MNS16A polymorphism with clinical outcomes of North Indian lung cancer patients undergoing platinum-based doublet chemotherapy.","authors":"Ishmeet Kaur, Heena Kansal, Sidhartha Singh, Navneet Singh, Siddharth Sharma","doi":"10.1007/s12094-024-03800-1","DOIUrl":"10.1007/s12094-024-03800-1","url":null,"abstract":"<p><strong>Background: </strong>Telomerase has been linked to aging and cancer. The MNS16A polymorphism in the hTERT gene plays a significant role in modulating telomerase activity and highlights the complexity of telomere-related genetics in cancer research.</p><p><strong>Experimental design: </strong>We genotyped 401 lung-cancer samples treated with platinum-based chemotherapy to identify the MNS16A polymorphism. We assessed overall survival using the Kaplan-Meier method and Cox regression analysis for adjusted hazard ratios. Stratified analyses evaluated risks for subgroups based on clinicopathologic parameters, outcomes, and toxicity calculated.</p><p><strong>Results: </strong>Our findings show no significant link between MNS16A polymorphism and lung-cancer survival. However, in squamous cell carcinoma (SQCC) patients, the SS genotype was associated with poorer survival (p = 0.004). Patients with LS + SS genotypes responded better to gemcitabine in univariate (p = 0.003) and multivariate analyses (p = 0.014). The LS genotype was linked to a lower risk of progression to stage 4 (p = 0.011) and metastasis (p = 0.015) but an increased risk of T4 tumor size (p = 0.026). No significant correlations were found between MNS16A polymorphism and treatment-related toxicities.</p><p><strong>Conclusion: </strong>The MNS16A polymorphism does not significantly impact overall lung-cancer survival but affects specific subgroups, influencing certain lung-cancer subtypes and treatment responses while having limited predictive value for overall outcomes or toxicity risks.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2605-2619"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741234","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":"Autophagy in cholangiocarcinoma: a comprehensive review about roles and regulatory mechanisms.","authors":"Yuxia Yang, Qiuyan Li, Lok Ting Chu, Xiaocong Lin, Helian Chen, Linsong Chen, Jinjing Tang, Tao Zeng","doi":"10.1007/s12094-024-03797-7","DOIUrl":"10.1007/s12094-024-03797-7","url":null,"abstract":"<p><p>The role of autophagy in cholangiocarcinogenesis and its development is intricate. Autophagy has a dual role in cholangiocarcinoma, and understanding the function and mechanism of autophagy in cholangiocarcinoma is pivotal in guiding therapeutic approaches to its treatment in clinical settings. Recent studies have revealed that autophagy is involved in the complex biological behavior of cholangiocarcinoma. In this review, we have summarized the genes and drugs that would promote or inhibit autophagy, leading to change in cellular behaviors of cholangiocarcinoma, including apoptosis, proliferation, invasion and migration, and influence its cellular drug resistance. In addition, we concluded the signaling pathways modulating autophagy in cholangiocarcinoma cells, including PI3K/AKT/mTOR,p38MAPK,AMPK/mTOR,LKB1-AMPK, and AKT/WNK1, and ERK signaling pathways, which subsequently impacting apoptosis, death, migration, invasion, and proliferation. In conclusion, we would like that we can provide ideas for future cholangiocarcinoma treatment by comprehensively summarizing the latest studies on the relationship between autophagy and cholangiocarcinoma, including the factors affecting autophagy and related signaling pathways.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2391-2400"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711645","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":"Analysis of therapeutic effects and influencing factors of ICIs in lung-cancer patients.","authors":"Jun Luo, Li Li, HongGui Wang, Xian Zhang, FangTing He, Meng Shi, Xin Zhang, Rui Tang, Yong Bao","doi":"10.1007/s12094-024-03767-z","DOIUrl":"10.1007/s12094-024-03767-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The aim of this retrospective study was to analyze the efficacy and risk factors of immune checkpoint inhibitors (ICIs) in lung cancer patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;One hundred lung cancer patients who were treated in our hospital from May 2021 to May 2023 were selected as the study subjects and divided into chemotherapy group (n = 50) and ICIs group (n = 50), in which the chemotherapy group was given the combined treatment of vincristine and cisplatin (NP), while the ICIs group was given ICIs for treatment. The therapeutic effect and adverse reactions (hypertriglyceridemia, anemia, hypertension and hypoproteinemia) of the two groups were compared, and fasting venous blood was collected. The levels of carcinoembryonic antigen (CEA) and cancer antigen 199 (CA199) were compared between the two groups before and after treatment. According to the therapeutic effect, 100 patients with lung cancer were divided into complete remission (CR) + partial remission (PR) group (n = 52) and stable (SD) + progressive (PD) group (n = 48). The clinical data and pathologic data of the two groups were compared.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The rates of objective effective rate (ORR) in chemotherapy group and ICIs group were 36.00% and 68.00% respectively, and the level of ORR in ICIs group was significantly higher than that in chemotherapy group, with statistical significance (P &lt; 0.05). There was no significant difference in serum CEA and CA199 levels between the two groups before operation (P &gt; 0.05). Three months after operation, the serum CEA and CA199 levels in ICIs group were significantly lower than those in chemotherapy group, and the difference was statistically significant (P &lt; 0.05). The adverse reactions of hypertriglyceridemia, anemia, hypertension and hypoproteinemia in chemotherapy group and ICIs group during treatment were all grade 1-2, and the incidence of adverse reactions was similar between the two groups (P &gt; 0.05). There was no significant difference in sex, age, anatomic position, pathologic type, smoking history and differentiation between the two groups (P &gt; 0.05). In SD + PD group, the preoperative maximum tumor diameter &gt; 4 cm, tumor node metastasis (TNM) stage IV, lactate dehydrogenase (LDH) ≥ 183 U/L, and tumor volume ≥ 120m&lt;sup&gt;3&lt;/sup&gt; were significantly higher than those in CR + PR group, and the prognostic nutritional index (PNI) ≥ 41.8 and the proportion of ICIs were significantly lower than those in CR + PR group, with statistical significance (P &lt; 0.05). Multifactorial logistic regression analysis showed that preoperative maximum tumor diameter &gt; 4 cm and LDH ≥ 183 U/L were risk factors for poor lung cancer outcome, and PNI ≥ 41.8 and ICIs treatment were protective factors for poor lung cancer outcome (P &lt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;ICIs is effective in the treatment of lung cancer, which can obviously reduce the tumor load and has high safety. In addition, the maximum t","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2597-2604"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669792","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":"Cancer and physical activity: facilitating counseling.","authors":"Alejandro Gómez-Bruton, José Manuel Granada-López, Elena Aguirre, Nuria Garatachea","doi":"10.1007/s12094-024-03795-9","DOIUrl":"10.1007/s12094-024-03795-9","url":null,"abstract":"<p><p>Recent studies suggest that only 27.6% of cancer survivors meet PA guidelines. This could partially be attributed to the limited knowledge reported by healthcare professionals (HCP) regarding the appropriate timing, methodology, and suitability of referring cancer survivors to exercise programs or professionals. In this commentary, we aim to acknowledge the challenges that HCP may face in prescribing exercise and propose potential solutions to facilitate their efforts in this regard.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2437-2440"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774457","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":"Recommendations for the use of nuclear medicine imaging in patients with neuroblastoma.","authors":"Raquel Sánchez-Vañó, Julia Balaguer, Isabel Borrego-Dorado, Alba Esteban-Figueruelo, Cristina Gámez, Raquel Hladun, Ricardo López-Almaraz, Mercedes L Llempén, Sonia Rodado, Pedro M Rubio-Aparicio","doi":"10.1007/s12094-024-03755-3","DOIUrl":"10.1007/s12094-024-03755-3","url":null,"abstract":"<p><p>Neuroblastoma (NB) is the most common extracranial solid cancer in children. Despite intensive multimodality treatment, long-term survival of patients with high-risk NB, which comprises more than half of all cases, remains poor. Nuclear medicine is key in diagnosis, staging, response assessment and long-term follow-up of NB. The emergence of novel tracers and the increasing complexity of studies require updated guidelines for nuclear medicine imaging in NB. Standardising diagnostic techniques are essential for improving study comparability and ensuring test quality. This article aims to provide a comprehensive review of NB radionuclide diagnostic imaging, including its characteristics, accuracy, advantages, and limitations. It offers practical recommendations to multidisciplinary teams responsible for treating patients with NB. This review summarises the opinions of leading experts from the Neuroblastoma Spanish Group within the Spanish Society of Paediatric Haematology and Oncology (SEHOP) and the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM).</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2401-2415"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606320","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":"Integrated analysis of single-cell and bulk RNA-sequencing identifies a metastasis-related gene signature for predicting prognosis in lung adenocarcinoma.","authors":"Xu Cao, Jingjing Xi, Congyue Wang, Wenjie Yu, Yanxia Wang, Jingjing Zhu, Kailin Xu, Di Pan, Chong Chen, Zhengxiang Han","doi":"10.1007/s12094-024-03752-6","DOIUrl":"10.1007/s12094-024-03752-6","url":null,"abstract":"<p><strong>Background: </strong>Metastasis has been documented as an independent and significant prognostic feature of lung adenocarcinoma (LUAD) patients. However, the underlying genetic and molecular mechanisms responsible for LUAD metastasis and their prognostic significance are not exactly defined.</p><p><strong>Methods: </strong>The single-cell transcriptomic profiles of primary and metastatic LUAD samples were integrated as a whole dataset. Enrichment analysis and pseudotime trajectory analysis were performed to illustrate the cellular origins and changes during the metastatic process. The LUAD metastasis-related genes (LMRGs) molecular cluster and signature was constructed through unsupervised consensus clustering and ten machine-learning algorithms in The Cancer Genome Atlas (TCGA) LUAD cohort using ten machine-learning algorithms. Validation of the signature was conducted using four independent cohorts from the Gene Expression Omnibus (GEO) database. Kaplan-Meier, ROC, univariate and multivariate Cox-regression analyses were performed to test the stability of the signature. The gene CCT6A was subjected to knockdown, followed by validation through western blot analysis, flow cytometry, wound healing and transwell-migration assays to determine its potential significance.</p><p><strong>Results: </strong>First, the signaling pathway networks remodeling and metabolic reprogramming were demonstrated to be involved in the metastasis of malignant LUAD cells, which facilitate their extravasation and adaptation to other organs. Furthermore, distinct subtypes of malignant LUAD cells exhibit tissue-specific patterns. Then, two distinct molecular patterns of LMRGs were established, which showed diverse prognoses. A LUAD metastasis-related gene signature (LMRGS) was constructed via a multiple machine-learning-based integrative procedure, which possesses distinctly superior accuracy than most common clinical features and 69 published prognostic signatures. The patients stratified by the signature into high-risk group had a significantly poorer prognosis compared to those in the low-risk group, and this was well validated across different clinical subgroups. In addition, the risk score calculated by LMRGS remained an independent prognostic parameter in both univariate and multivariate Cox regression. Notably, knockdown of CCT6A gene promoted cell apoptosis and decelerated the cell migration obviously.</p><p><strong>Conclusion: </strong>LMRGS could serve as a novel and promising tool to improve clinical outcomes for individual LUAD patients.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2579-2596"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631894","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}