Clinical & Translational Oncology最新文献

{"title":"Development of a prediction model for recurrent parathyroid carcinoma lesions based on 3D-EnCT and ultrasound imaging features.","authors":"Xing Liu, Wenjing Yang, Teng Zhao, Qian Wang, Jiacheng Wang, Dalin Feng, Li Zhao, Hong Shen, Rongfang Shen, Ren Lang, Bojun Wei","doi":"10.1007/s12094-024-03787-9","DOIUrl":"https://doi.org/10.1007/s12094-024-03787-9","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to analyze the three-dimensional enhanced computed tomography (3D-EnCT) and ultrasound imaging features of recurrent parathyroid carcinoma lesions and develop a prediction model based on these features.</p><p><strong>Methods: </strong>The clinical data of 34 patients (48 cases) with recurrent parathyroid carcinoma who underwent surgical treatment at Beijing Chaoyang Hospital's Thyroid and Neck Surgery Department between January 2017 and April 2024 were retrospectively analyzed. A total of 103 suspicious lesions were identified through a combination of preoperative 3D-EnCT and ultrasound examinations. Patients admitted prior to 1 January 2023 were included in the training set, and those admitted after 1 January 2023 were included in the validation set. In the training set, lesions were categorized as positive or negative based on pathological analysis. Statistically significant imaging features were identified via intergroup comparisons. An imaging prediction model was developed based on the 3D-EnCT and ultrasound features, and the predictive performance of the model was evaluated via receiver operating characteristic curves in the validation set.</p><p><strong>Results: </strong>Arterial- and venous-phase CT values, lesion boundaries, and blood flow signals were associated with pathological positivity. The 3D-EnCT prediction model based on these features achieved areas under the curve (AUCs) of 0.9 and 0.714 in the training and validation sets, respectively, whereas the ultrasound prediction model achieved AUCs of 0.601 and 0.621, respectively. The 3D-EnCT model demonstrated superior predictive performance.</p><p><strong>Conclusion: </strong>The 3D-EnCT prediction model demonstrated superior predictive performance for recurrent parathyroid carcinoma lesions.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677546","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":"Development of B7-H3 targeted CAR-T cells for renal cell carcinoma therapy: in vitro and in vivo efficacy.","authors":"Wenyi Deng, Lvying Wu, Liuyan Chen, Kuanyin Wang, Na Lin, Lingfeng Zhu, Jin Chen","doi":"10.1007/s12094-024-03792-y","DOIUrl":"10.1007/s12094-024-03792-y","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to develop chimeric antigen receptor (CAR)-T cells specifically targeting B7-H3-expressing renal cell carcinoma (RCC) and to evaluate the feasibility of B7-H3 CAR-T therapy for RCC.</p><p><strong>Methods: </strong>We analyzed B7-H3 expression in RCC using bioinformatics approaches and confirmed it in tissues and cell lines through immunohistochemical staining and Western blot analysis. A lentiviral vector containing a B7-H3 specific CAR was constructed and transfected into human T cells, with CAR expression verified by flow cytometry. Cytotoxic efficacy was evaluated in co-culture experiments, measuring the production of interferon-gamma (IFN-γ), interleukin-2 (IL-2), granzyme B, and lactate dehydrogenase (LDH) release. Xenograft models in nude mice were used to evaluate tumor growth inhibition by B7-H3 CAR-T cells.</p><p><strong>Results: </strong>B7-H3 was significantly expressed in RCC and associated with poor prognosis. Elevated levels of B7-H3 expression were validated in both RCC tissues and cell lines. A B7-H3-specific CAR-T cell was developed, achieving a CAR transduction efficiency of 39.85%, as assessed by flow cytometry. In vitro co-culture assays demonstrated that the CAR-T cells exhibited substantial cytotoxic activity against RCC cell lines, with this activity positively correlating with the effector-to-target ratio. Furthermore, the secretion levels of IFN-γ, IL-2, granzyme B, and LDH were significantly increased compared to the control groups. In vivo experiments further confirmed that B7-H3 CAR-T cells significantly inhibited tumor growth.</p><p><strong>Conclusion: </strong>The current study suggests that B7-H3 CAR-T cells exhibit significant efficacy in targeting and eliminating RCC cells, indicating a promising cellular immunotherapy approach for RCC treatment.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669804","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":"Correction: Prediction model for major bleeding in anticoagulated patients with cancer-associated venous thromboembolism using machine learning and natural language processing.","authors":"Andrés J Muñoz Martín, Ramón Lecumberri, Juan Carlos Souto, Berta Obispo, Antonio Sanchez, Jorge Aparicio, Cristina Aguayo, David Gutierrez, Andrés García Palomo, Diego Benavent, Miren Taberna, María Carmen Viñuela-Benéitez, Daniel Arumi, Miguel Ángel Hernández-Presa","doi":"10.1007/s12094-024-03780-2","DOIUrl":"10.1007/s12094-024-03780-2","url":null,"abstract":"","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669799","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":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-19","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":"Correction: Impact of a comprehensive geriatric assessment to manage elderly patients with locally advanced non-small-cell lung cancers: a multicenter prospective study.","authors":"Maria Arnal Rondan, Alfredo Sánchez-Hernández, David Lorente Estellés, Jóse García Sánchez, Francisco de Asís Aparisi Aparisi, Jorge Soler López, Raquel Ten Benajes, Regina Gironés Sarrió","doi":"10.1007/s12094-024-03766-0","DOIUrl":"https://doi.org/10.1007/s12094-024-03766-0","url":null,"abstract":"","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644950","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":"Decoding β-catenin expression patterns in ovarian serous carcinoma with clinicopathological implications: insights from National Cancer Institute.","authors":"Noura A A Ebrahim, Amany A Abou-Bakr, Hassan N Tawfik, Hanan R Nassar, Iman Adel","doi":"10.1007/s12094-024-03770-4","DOIUrl":"https://doi.org/10.1007/s12094-024-03770-4","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to examine the immunohistochemical expression of β-catenin in serous ovarian carcinoma and to investigate its relationship with clinicopathological features and disease outcomes.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 67 cases of serous ovarian carcinoma diagnosed at the Pathology Department of the Egyptian National Cancer Institute, Cairo University, between January 1, 2015, and December 31, 2017.</p><p><strong>Results: </strong>The age of the patients ranged from 26 to 76 years. Aberrant β-catenin expression was defined by the presence of cytoplasmic staining with or without membranous staining in at least 10% of tumor cells. Of the cases analyzed, thirty exhibited cytoplasmic staining, 18 demonstrated preserved expression on the cell membrane, 15 showed combined cytoplasmic and membranous staining, while four cases were entirely negative. Significant correlations were observed between β-catenin positivity and both tumor grade and p53 expression, with p values of 0.004 for each correlation.</p><p><strong>Conclusions: </strong>Positive β-catenin expression significantly correlated with tumor grade in serous ovarian carcinoma. Most low-grade serous carcinoma cases exhibited membranous β-catenin expression, whereas high-grade serous carcinoma cases predominantly displayed cytoplasmic staining. Therapeutic strategies aimed at inhibiting β-catenin signaling could provide a novel approach to improving outcomes for patients with high-grade ovarian cancer.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631880","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":"A prognostic nomogram for patients with III-IV nasopharyngeal carcinoma based on dynamic changes in the inflammatory and nutrition index.","authors":"Guangyi Cheng, Shiwang Yuan, Jiang Wang, Sijia Deng, Yang Wu, Yuyan Wang, Yu Shen, Liantao Li","doi":"10.1007/s12094-024-03781-1","DOIUrl":"https://doi.org/10.1007/s12094-024-03781-1","url":null,"abstract":"<p><strong>Background: </strong>The purpose of the study was to explore the value of dynamic changes in inflammatory and nutritional index after comprehensive treatment in patients with stage III-IVA nasopharyngeal carcinoma (NPC). A prognostic model was also established and validated for progression-free survival (PFS) of patients.</p><p><strong>Methods: </strong>We retrospectively selected 279 NPC patients with stage III-IVA. Their general clinical data and hematological index were collected and then calculated the changes during treatment. X-tile software was used to determine the optimal cut-off value. COX regression, Lasso method, and Boruta method were used to variable selection and model establishment. Using the bootstrap internal validation method, concordance index (C-index), calibration plot, and Kaplan-Meier curves were used to evaluate the model. To test the prognostic value of the model, we have also evaluated the performance of the nomogram against a conventional tumor metastasis staging system (TNM).</p><p><strong>Results: </strong>Multivariable COX regression analysis demonstrated that clinical staging, delta lymphocyte, delta monocyte, delta albumin, delta platelet-to-lymphocyte ratio and delta systemic immune inflammation index were related to the PFS of NPC patients. The C-index of the model was 0.712, and the calibration curve indicated that the model had good consistency. The C-index of the TNM staging system was 0.597, which was considerably lower compared to our model (P = 0.015).</p><p><strong>Conclusion: </strong>We demonstrated the predictive value of dynamic changes in inflammatory and nutritional indices for the prognosis of NPC by successfully establishing and validating a prognostic model for predicting 1- and 3-year PFS after comprehensive treatment in patients with stage III-IVA NPC.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631875","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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-11","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":"Application of CAR-T cell therapy in B-cell lymphoma: a meta-analysis of randomized controlled trials.","authors":"Xiao-Jing Yu, Chang Liu, Shi-Zhi Hu, Zhan-Yuan Yuan, Hai-Yan Ni, Sheng-Jia Sun, Cheng-Yang Hu, He-Qin Zhan","doi":"10.1007/s12094-024-03774-0","DOIUrl":"https://doi.org/10.1007/s12094-024-03774-0","url":null,"abstract":"<p><strong>Background: </strong>This study aims to compare the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) immunotherapy with standard treatment for B-cell lymphoma, providing evidence-based support for the more efficient use of CAR-T cell immunotherapy.</p><p><strong>Methods: </strong>We conducted a comprehensive literature search of high-quality randomized controlled trials (RCTs) on CAR-T therapy for B-cell lymphoma in the following databases: Wanfang, Web of Science, CNKI, VIP database, and PubMed, up to February 2024. The outcome measures included objective remission rate (ORR), complete remission rate (CRR), and incidence of adverse reactions. Subgroup analysis was performed based on the differences in co-stimulatory domains. Meta-analysis was conducted using Review Manager 5.4 and Stata software.</p><p><strong>Results: </strong>A total of five RCTs involving 1670 patients were included in this meta-analysis. The results showed that the CAR-T treatment group had significantly higher ORR (RR: 1.47, 95% CI 1.23-1.76, I² = 80%, p < 0.0001), CRR (RR: 2.19, 95% CI 2.16-3.79, I² = 93%, p = 0.005), cytokine release syndrome (CRS) incidence (RR: 34.51, 95% CI 2.27-523.78, I² = 98%, p = 0.01), neurotoxicity (NT) incidence (RR: 6.00, 95% CI 1.82-19.75, I² = 80%, p = 0.003), neutropenia incidence (RR: 1.39, 95% CI 1.02-1.88, I² = 93%, p = 0.03), leukopenia incidence (RR: 1.39, 95% CI 1.04-1.87, I² = 61%, p = 0.03), and headache incidence (RR: 1.56, 95% CI 1.25-1.95, I² = 34%, p < 0.0001) compared to the standard treatment group. Subgroup analysis based on co-stimulatory domains revealed that the 4-1BB subgroup had higher incidences of CRR, CRS, NT and leukopenia than the CD28 subgroup; however, the CD28 subgroup exhibited higher ORR and neutropenia than the 4-1BB subgroup.</p><p><strong>Conclusion: </strong>CAR-T cell immunotherapy demonstrates superior efficacy compared to standard therapy in treating B-cell lymphoma. However, CAR-T treatment can lead to adverse reactions such as CRS and NT. Infusion of an appropriate dose of CAR-T cells (e.g., 100 × 10⁶) may be a strategy to mitigate the risk of CRS and NT.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606305","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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-08","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}