Translational cancer research最新文献

{"title":"Differences in esophageal adenocarcinoma survival and treatment modalities by III/IV stage subgroup: a SEER population-based study.","authors":"Cheng Gong, Zhidong Wang, Ce Chao, Min Wang, Yongxiang Qian, Dongmei Di, Yang Liu","doi":"10.21037/tcr-24-2099","DOIUrl":"https://doi.org/10.21037/tcr-24-2099","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer (EC) is an aggressive gastrointestinal carcinoma with high morbidity and mortality worldwide. This study was aimed at investigating the influences of T stage in patients with the same III/IV stage, and of various therapeutic modalities in each subgroup of III/IV stage in esophageal adenocarcinoma (EAC).</p><p><strong>Methods: </strong>Patients diagnosed with EAC between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression models were used to select independent prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier survival curves were used to determine survival differences according to T stage and treatment strategy in the III/IV stage subgroup.</p><p><strong>Results: </strong>Data from 5,765 EACs were identified. Seven independent risk factors were identified for OS and CSS. Based on T stage, patients with the same III/IV stage showed survival differences in the subgroup analyses in both OS and CSS (P<0.001). The median survival time in T2N1M0 in III stage and T1N2-3M0 in IVA stage was longer compared to the other groups, respectively. Concerning therapy modalities, chemotherapy alone or surgery alone showed a significant difference in terms of CSS in III stage subgroups (P<0.001, P=0.01, respectively), while surgery combined with chemotherapy also showed a significant difference (P=0.02). However, no survival difference was found in the subgroups of IVA stage based on therapy. Finally, chemotherapy plus surgery in early stages of III/IVA subgroups prominently increased the median survival time.</p><p><strong>Conclusions: </strong>Differences according to T stage may potentially influence EAC survival under the same III/IV stage. Our findings implied that higher T stage was associated with poorer prognosis among patients in the same III/IVA stage. Meanwhile, it was advised for patients to receive surgery plus chemotherapy in the early subgroups of III/IVA stage.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"2615-2625"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317908","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":"The lncRNA MIR22HG suppresses prostate cancer cell proliferation, migration, and epithelial-mesenchymal transition via the miR-4428/PCDH9 axis.","authors":"Ansu Li, Wu Sun, Shihe Shao, Xuefeng Qiu, Jianpeng Hu, Feilun Cui","doi":"10.21037/tcr-2024-2200","DOIUrl":"https://doi.org/10.21037/tcr-2024-2200","url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNAs (lncRNAs) play crucial roles in modulating the development and progression of human malignant cancers. As a tumour suppressor gene, the lncRNA MIR22HG has been identified in many kinds of cancers. However, the specific function of MIR22HG in prostate cancer (Pca) has yet to be elucidated. Specifically, we sought to determine whether MIR22HG plays a role in Pca progression and the underlying mechanisms involved.</p><p><strong>Methods: </strong>Differentially expressed lncRNAs in Pca tissues were screened by sequencing, and the expression of MIR22HG in cells and tissues was determined via quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK8), Transwell, and western blotting assays were used to determine whether Pca cell proliferation and migration can be regulated by the MIR22HG/microRNA-4428 (miR-4428)/PCDH9 axis. To investigate tumour growth <i>in vivo</i>, we constructed tumour subcutaneous xenograft models. Moreover, we performed bioinformatic analysis and dual-luciferase reporter assays to verify the expression of the miR-4428 and PCDH9 targets.</p><p><strong>Results: </strong>MIR22HG was expressed at low levels in Pca cells and tissues, and its upregulation inhibited cell proliferation and migration and prevented epithelial-mesenchymal transition (EMT) <i>in vivo</i> and <i>in vitro</i>. A negative correlation was found between MIR22HG expression and miR-4428 expression. The downstream target gene of miR-4428 was PCDH9. Therefore, MIR22HG may function as a competing endogenous RNA (ceRNA) to regulate miR-4428/PCDH9.</p><p><strong>Conclusions: </strong>We demonstrated that MIR22HG acts as a tumour suppressor in Pca and suggested that targeting the MIR22HG/miR-4428/PCDH9 axis may be a new avenue for Pca therapy.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"3133-3148"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317962","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":"Construction of a prognostic model for lung adenocarcinoma based on necroptosis genes and its exploration of the potential for tumor immunotherapy.","authors":"Xiaoling Liu, Xin Li, Xiufen Shen, Run Ma, Zhuo Wang, Ying Hu","doi":"10.21037/tcr-24-2165","DOIUrl":"https://doi.org/10.21037/tcr-24-2165","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer ranks among the most prevalent malignancies globally, with lung adenocarcinoma (LUAD) being its most frequent histological subtype. Necroptosis is a newly defined mode of programmed cell death that is different from apoptosis and necrosis. However, the role of necroptosis in the occurrence and development of LUAD remains largely unexplored. This study aimed to construct a prognostic model of LUAD based on necroptosis-related genes (NRGs) and analyze the predictive value of this model on the prognosis of LUAD patients.</p><p><strong>Methods: </strong>The dataset of LUAD patients was downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, and the NRGs were downloaded from inside GeneCards and Harmonizome databases. LUAD prognostic models were constructed by one-way Cox analysis, least absolute shrinkage and selection operator (LASSO) regression analysis and multifactorial Cox regression analysis. Differential analyses of immune function as well as common tumor drugs were performed between high and low risk groups. A ceRNA was constructed to explore the potential lncRNA-miRNA-mRNA regulatory axis in LUAD. In this study, we leveraged bioinformatics to pinpoint genes implicated in necroptosis within LUAD.</p><p><strong>Results: </strong>Two differentially expressed NRGs (DENRGs: KL, PLK1) were screened and used to construct the prognostic model and validate the RiskScore as an independent prognostic factor. Gene set variation analysis (GSVA) analysis showed that differentially expressed genes were mainly enriched in immune-related pathways. Additionally, we conducted experimental assays to validate the expression of these genes in LUAD cell lines. The GSVA analysis showed that differentially expressed genes were mainly enriched in immune-related pathways. Significant differences (P<0.05) were found between the high and low risk groups in terms of immune function and half-maximal inhibitory concentration (IC₅₀) values of five anticancer drugs (doxorubicin, lapatinib, paclitaxel, savolitinib and trametinib). We also identified a lncRNA SNHG14 /hsa-miR-101-3p/KL/PLK1 regulatory axis for LUAD.</p><p><strong>Conclusions: </strong>The survival prognosis model of NRGs constructed in this study can predict the prognosis and immune microenvironment of LUAD patients.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"2563-2579"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317937","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":"Novel combinations with programmed cell death 1 inhibitor for incurable recurrent/metastatic head and neck squamous cell carcinoma (RM HNSCC): is cabozantinib a front runner?","authors":"Priyanka Bhateja, Marcelo Bonomi, Claire Verschraegen","doi":"10.21037/tcr-2024-2569","DOIUrl":"https://doi.org/10.21037/tcr-2024-2569","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"2548-2552"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317947","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":"Endobronchial malignancy as a manifestation of advanced ovarian cancer recurrence: a case report and literature review.","authors":"Dongrui Zhang, Li Yang, Alexandros Laios, Wei Jia","doi":"10.21037/tcr-24-507","DOIUrl":"https://doi.org/10.21037/tcr-24-507","url":null,"abstract":"<p><strong>Background: </strong>Endobronchial metastasis from primary ovarian cancer (OC) is very rare. To enhance our understanding of this disease, we present a case report and retrospective analysis of a patient with a bronchial tumor as a manifestation of primary OC recurrence.</p><p><strong>Case description: </strong>A 51-year-old woman presented with a history of intermittent cough and expectoration over 3 months by suffocating pneumonia for 3 weeks. Chest X-ray revealed multiple nodular masses at the right upper lobe, soft tissue thickening with bronchial invasion in the left upper lobe, enlargement of the right and left upper hilar, spreading mediastinum, and elevated right septum. Bronchoscopy identified stenosis in the right main bronchus opening with obstruction of the apical, middle, and posterior segmental bronchi in the opening of left main bronchus by a visible neoplasm. Biopsy of the endobronchial lesion was akin to metastatic OC. Indeed, the patient was previously treated for advanced OC with enlarged left supraclavicular nodules [International Federation of Gynecology and Obstetrics (FIGO) stage 4B]. The treatment includes surgical resection of the uterus, fallopian tubes, ovaries, omentum, and left supraclavicular lymph nodes, as well as chemotherapy before and after surgery. Unfortunately, further chemotherapy was discontinued due to intolerance. Rapid disease progression occurred leading to her late self-referral and admission, decision for palliation, ultimately resulting in her demise.</p><p><strong>Conclusions: </strong>Flexible bronchoscopy combined with imaging and immunohistochemistry tests proves to be an effective diagnostic strategy for identifying endobronchial metastasis in OC patients. Endobronchial intervention, radiotherapy, and chemotherapy emerge as viable treatment modalities for these patients. The prognosis of OC patients with an endobronchial metastasis as a manifestation of recurrent disease should be considered in the context of their advanced disease despite available active treatment modalities.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"3255-3262"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317911","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":"Erratum: The prognostic significance of fragile X mental retardation syndrome-related protein 1 (FXR1) in breast cancer.","authors":"","doi":"10.21037/tcr-2025b-4","DOIUrl":"https://doi.org/10.21037/tcr-2025b-4","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.21037/tcr-24-1542.].</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"3263"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317913","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":"The prognostic and immune significance of fibronectin type III domain-containing 1 gene in pan-cancer and its relationship with proliferation and migration of stomach adenocarcinoma.","authors":"Minying Deng, Wen Huang, Rongkui Luo, Huimei Wang, Zixiang Yu, Benting Ma, Lei Xu, Xiaolei Zhang, Jieakesu Su, Chen Xu, Yingyong Hou","doi":"10.21037/tcr-2024-2279","DOIUrl":"https://doi.org/10.21037/tcr-2024-2279","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Fibronectin type III domain containing 1 (FNDC1) exhibits emerging roles in tumorigenesis, yet its pan-cancer implications and mechanistic contributions to stomach adenocarcinoma (STAD) remain underexplored. This study systematically evaluates FNDC1's prognostic relevance, immune interactions, and functional impact in STAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Multi-omics analyses integrated FNDC1 expression, mutation profiles, and immune associations across 33 cancers using The Cancer Genome Atlas (TCGA) data. Immunohistochemistry assessed FNDC1, mismatch repair (MMR) protein, and human epidermal growth factor receptor 2 (HER2), and clinicopathological information was collected for statistical analysis. Finally, we conducted in vitro experiments to assess the effects of FNDC1 knockdown on STAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In various cancers, the main genetic alterations of &lt;i&gt;FNDC1&lt;/i&gt; are mutations and deep deletions, with a mutation frequency of 10% observed primarily in malignant melanoma and endometrial carcinoma. The expression levels of &lt;i&gt;FNDC1&lt;/i&gt; messenger RNA (mRNA) in breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), and STAD are significantly higher than those in adjacent normal tissues (P&lt;0.05). In STAD, FNDC1 shows significant correlations with cell infiltrations such as endothelial cells, eosinophils, granulocyte-monocyte progenitors, hematopoietic stem cells, macrophage M1, macrophage M2, monocytes, myeloid dendritic cells, and activated myeloid dendritic cells. In STAD, FNDC1 exhibits significant positive correlations with immune checkpoints HAVCR2 and PDCD1LG2. Proteins with similar expression patterns to FNDC1 and ranking in the top 100 include GNAS, GNB1, MXRA5, COL3A1, COL10A1, ASPN, SFRP2, SFRP4, FXYD2, and GNG2. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis shows that in STAD, &lt;i&gt;FNDC1&lt;/i&gt;-related genes are involved in pathways such as neuroactive ligand-receptor interaction, calcium signaling, cAMP signaling, vascular smooth muscle contraction, and pancreatic secretion. Gene Ontology (GO) functional enrichment analysis in STAD shows that FNDC1-related genes are involved in pathways related to the muscle system process, collagen-containing extracellular matrix, and receptor ligand activity. Clinical sample analysis demonstrates that FNDC1 protein is upregulated in STAD compared to adjacent normal tissues (P&lt;0.05). Age, tumor size, tumor differentiation, Lauren classification, lymphovascular invasion, neural invasion, tumor deposit, postoperative recurrence, T stage, N stage, M stage, tumor-node-metastasis (TNM) stage, HER2 expression, and MMR protein expression are relevant risk factors for poor prognosis in STAD patients, with age, tumor size, Lauren classification, lymphovascular invasion, neural invasion","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"3069-3095"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317963","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":"When is belzutifan the right option for von Hippel-Lindau disease-associated hemangioblastomas?-a critical review of LITESPARK-004 results.","authors":"Ugur Sener, Taylor Galloway","doi":"10.21037/tcr-2024-2478","DOIUrl":"https://doi.org/10.21037/tcr-2024-2478","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"2558-2562"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317967","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 real-world retrospective cohort study: the clinical outcomes and characteristics of platinum-resistant recurrent ovarian cancer.","authors":"Qing Wang, Lei Kuang, Boyang Liu, Qi Chen, Yanyu Li, Jiayun Zhou, Jingbo Zhang, Xinhui Yang, Guiping Wan, Jörg Wischhusen, Rosa A Salcedo-Hernández, Colton Ladbury, Zeyuan Yin, Bei Zhang","doi":"10.21037/tcr-2025-641","DOIUrl":"https://doi.org/10.21037/tcr-2025-641","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Current clinical research on platinum-resistant recurrent ovarian cancer (PRROC) is primarily based on prospective clinical trials, while real-world evidence remains extremely scarce. The continuous accumulation of real-world evidence can effectively address the limitations of clinical trials, and real-world evidence is increasingly gaining recognition in guiding clinical practice. This study sought to describe the clinical outcomes and characteristics of patients diagnosed with PRROC in a real-world setting. Comparing clinical outcomes [e.g., progression-free survival (PFS) and overall survival (OS)] of PRROC patients provides researchers with valuable insights into the current treatment status, effectiveness, and contributory factors of PRROC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Patients with histologically confirmed diagnosis of OC from six tertiary referral centers in China from January 2018 to December 2023 were recruited at diagnosis of PRROC. All study patients were followed up to December 1, 2023. We evaluated the characteristics, treatment patterns, and outcomes of these patients. In addition, the background characteristics of the patients were identified, and independent prognostic factors for OS were investigated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In this cohort of 504 patients diagnosed with PRROC, 277 patients (54.96%) received a single-agent non-platinum chemotherapy, and 227 patients (45.04%) received a platinum-containing regimen. Compared to the single-agent non-platinum chemotherapy group, the platinum-based combination chemotherapy group had significantly longer PFS [5.6 vs. 4.0 months, hazard ratio (HR): 0.431, 95% confidence interval (CI): 0.356-0.521, P&lt;0.0001] and OS (15.9 &lt;i&gt;vs.&lt;/i&gt; 13.0 months; HR: 0.766, 95% CI: 0.638-0.919, P=0.005). The poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) monotherapy group tended to have not statistically significant improvement PFS (4.5 &lt;i&gt;vs.&lt;/i&gt; 4.0 months; HR: 0.788, 95% CI: 0.573-1.085, P=0.15) and OS (13.1 &lt;i&gt;vs.&lt;/i&gt; 13.0 months; HR: 1.101, 95% CI: 0.767-1.580, P=0.56) compared to the single-agent non-platinum chemotherapy group. Adding antiangiogenic therapy to platinum-based combination chemotherapy and single-agent non-platinum chemotherapy resulted in improved treatment efficiencies. Independent prognostic factors for OS were the progression-free interval (PFI), histological type, and clinical trial participation. In the subgroup of patients who received platinum-based combination chemotherapy, the patients with a PFI &gt;3-6 months who were re-treated with platinum-based chemotherapy had longer OS than those with a PFI &gt;0-3 months (16.47 &lt;i&gt;vs.&lt;/i&gt; 12.83 months, HR: 1.522, 95% CI: 1.155-2.006, P=0.003).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this real-world cohort, we found that patients diagnosed with PRROC, particularly those with a PFI of &gt;3-6 months, experienced substantial benefits from the re-administration of platinum agents. Thus, p","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"3161-3174"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317924","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":"Integrated analysis of uterine leiomyosarcoma and leiomyoma utilizing TCGA and GEO data: a WGCNA and machine learning approach.","authors":"Zixin Yang, Fan Yang, Fanlin Li, Ying Zheng","doi":"10.21037/tcr-2024-2465","DOIUrl":"https://doi.org/10.21037/tcr-2024-2465","url":null,"abstract":"<p><strong>Background: </strong>Uterine sarcoma is a gynecological mesenchymal tumor with an elusive pathogenesis. The uterine leiomyosarcoma (LMS) is the most common subtype of uterine sarcoma. LMS is a highly aggressive tumor with a poor prognosis. The genomic landscape of LMS remains unclear. Rare cases of LMS are observed to arise from leiomyoma (LM). We conducted a study to explore the genomic relationship between LMS and LM using public microarray data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Using bioinformatics analysis tools, we would like to provide molecular insight into the pathogenesis of LMS and to discover novel predictive biomarkers for this disease.</p><p><strong>Methods: </strong>LMS and LM differentially expressed genes (DEGs) were screened by analyzing GEO datasets; GSE764, GSE68312 and GSE64763; and TCGA data. A protein-protein interaction (PPI) network was constructed, and hub genes were identified utilizing the CytoHubba plug-in from Cytoscape software. In addition, weighted gene co-expression network analysis (WGCNA) was performed to identify hub genes. We took the intersection of the hub genes generated from the PPI network and WGCNA. Subsequently, random forest (RF) and support vector machine (SVM) algorithms were used to screen for key genes as predictive biomarkers. Finally, we constructed a nomogram with these genes.</p><p><strong>Results: </strong>A total of 37 hub genes were selected using WGCNA. A total of 245 DEGs were identified; 63 DEGs were upregulated, and 182 DEGs were downregulated. Functional enrichment analysis revealed that these genes were mainly associated with the cell cycle, extracellular matrix receptor interactions and oocyte meiosis. The final hub genes were <i>CENPA, KIF2C, TTK, MELK</i> and <i>CDC20</i>. Gene set enrichment analysis (GSEA) revealed that these genes were mostly enriched in the cell cycle, mismatch repair and amino sugar and nucleotide sugar metabolism. Tumor-infiltrating immune cell analysis indicated that these genes did not have an obvious correlation with immune cells.</p><p><strong>Conclusions: </strong><i>CENPA, KIF2C, TTK, MELK</i> and <i>CDC20</i> were key genes significantly associated with LMS and LM. Functional enrichment analysis and tumor-infiltrating immune cell analysis indicated that these genes might be correlated with tumor proliferation, which might shed light on the possible pathogenesis and predictive biomarkers of LMS.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"2999-3016"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317934","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}