Frontiers in Oncology最新文献

{"title":"Case Report: A giant dedifferentiated liposarcoma in the retroperitoneum.","authors":"Jinglin Xu, Linru Yang, Haoyang Zhang, Qingliang Hu, Yuan Shen, Jian Yang, Mingxu Da","doi":"10.3389/fonc.2026.1751424","DOIUrl":"https://doi.org/10.3389/fonc.2026.1751424","url":null,"abstract":"<p><p>This article presents a 60-year-old woman presented with a one-year history of abdominal distension, which acutely worsened over four days prior to admission. Imaging revealed a large retroperitoneal liposarcoma. Exploratory laparotomy identified a massive tumor (approximately 45×40×13 cm, weighing 8 kg) invading the left kidney, adrenal gland, adnexa, left hemicolon, and mesentery. En bloc resection was performed. Postoperative pathology combined with fluorescence <i>in situ</i> hybridization (FISH) testing demonstrated MDM2/CDK4 amplification, confirming dedifferentiated liposarcoma (DDLPS). The patient recovered well postoperatively and was discharged following adjuvant radiotherapy (IMRT; 50 Gy in 25 fractions), chemotherapy (AD regimen), and immunotherapy (sintilimab).Through this case, we mainly understand the characteristics of the disease onset, special diagnosis, and main treatment methods.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1751424"},"PeriodicalIF":3.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836171","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":"NSUN3 promotes oral squamous cell carcinoma progression through autophagy activation and FOXO pathway modulation.","authors":"Chengtao Wang, Lang Cheng, Lei Wang, Tao Luo, Yuxin Xie, Junliang Chen, Shuangjiang Wu","doi":"10.3389/fonc.2026.1807220","DOIUrl":"https://doi.org/10.3389/fonc.2026.1807220","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is a prevalent malignancy with high rates of lymph node metastasis and recurrence, contributing to persistently poor clinical outcomes. RNA 5-methylcytosine (m⁵C) modification, mediated by methyltransferases such as NSUN3, is implicated in tumor progression; however, the specific function of NSUN3 in OSCC remains largely unexplored. Autophagy plays a dual role in cancer, and the FOXO pathway is a key regulator of autophagy. This study aimed to elucidate the function of NSUN3 in OSCC and its potential mechanism involving autophagy and FOXO signaling.</p><p><strong>Methods: </strong>NSUN3 expression profiles were characterized in OSCC tissues and cell lines using immunohistochemistry, qRT-PCR, and Western blot. Clinicopathological correlations and survival analyses were performed on a cohort of 60 OSCC patients. NSUN3 was knocked down in SCC15 and SCC25 cells using lentiviral shRNA. Cell proliferation, migration, and invasion were assessed by CCK-8, wound-healing, and Transwell assays. Autophagy activity was evaluated by immunofluorescence (LC3 puncta formation), electron microscopy (autophagosome quantification), and Western blot (LC3-II/I ratio, Beclin1, P62/SQSTM1). The autophagy agonist rapamycin was used to rescue phenotypic changes. The activity of the FOXO pathway was assessed by detecting phospho-FOXO1/FOXO3.</p><p><strong>Results: </strong>NSUN3 was significantly upregulated in OSCC tissues and cells. Elevated NSUN3 expression, along with advanced pTNM stage and lymph node metastasis, constituted independent risk factors for poor overall survival. NSUN3 knockdown suppressed OSCC cell proliferation, migration, and invasion. Mechanistically, NSUN3 depletion inhibited autophagy, as evidenced by reduced LC3 puncta, decreased autophagosome number, lower Beclin1 expression, a reduced LC3-II/I ratio, and increased P62/SQSTM1 levels. Rapamycin treatment reversed these effects and partially restored malignant phenotypes. Furthermore, NSUN3 knockdown increased the phosphorylation (inactivation) of FOXO1 and FOXO3, thereby suppressing the FOXO signaling pathway.</p><p><strong>Conclusion: </strong>NSUN3 is overexpressed in OSCC and is an independent prognostic factor. It promotes OSCC progression by enhancing autophagy, potentially through modulating the FOXO pathway. Targeting NSUN3 may represent a novel therapeutic strategy for OSCC.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1807220"},"PeriodicalIF":3.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836210","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":"ITPKA suppresses glioma progression and predicts patient prognosis.","authors":"Naiyue Zhang, Min Peng, Jun Liu, Shizhang Ling","doi":"10.3389/fonc.2026.1802857","DOIUrl":"https://doi.org/10.3389/fonc.2026.1802857","url":null,"abstract":"<p><strong>Background: </strong>Inositol 1,4,5-trisphosphate 3-kinase A (ITPKA) is expressed in various tumors and is associated with tumor progression. This study investigated the expression patterns of ITPKA in gliomas and explored its functional role in glioblastoma (GBM), thereby providing new insights into the diagnostic and prognostic evaluations of ITPKA in this disease.</p><p><strong>Methods: </strong>ITPKA expression levels in glioma tissues of different World Health Organization (WHO) grades and GBM cell lines were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting. U251-MG and T98G cells were transfected with negative control, ITPKA overexpression or ITPKA knockdown plasmids, followed by relevant detections. Subsequently, the viability, proliferation, migration and invasion abilities, cell cycle progression, and apoptosis rate of GBM cells in each group were detected using the Cell-Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) proliferation, wound healing, Transwell, and flow cytometry assays, respectively. Subsequently, the effect of ITPKA on GBM growth was evaluated in a nude mouse subcutaneous tumor xenograft model.</p><p><strong>Results: </strong>Overexpression of ITPKA significantly inhibited the proliferation, migration, and invasion capabilities of GBM cells of the two GBM cell lines <i>in vitro</i> and the progression of subcutaneous xenograft tumors of two GBM cell lines in nude mice <i>in vivo</i>. In contrast, ITPKA knockdown significantly promoted the proliferation, migration, and invasion capabilities of GBM cells in the two GBM cell lines <i>in vitro</i> and the progression of subcutaneous xenograft tumors in these two GBM cell lines in nude mice.</p><p><strong>Conclusions: </strong>Low expression of ITPKA in glioma tissues correlates with GBM progression, indicating that it may act as a tumor suppressor gene and is a candidate biomarker for the molecular diagnostic and prognostic evaluations of glioblastoma.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1802857"},"PeriodicalIF":3.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835983","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":"Impact of educational intervention on the uptake of self-sampling for HPV test-based cervical cancer screening.","authors":"Adeola Akintola, Eileen O Dareng, Sally N Adebamowo, Clement A Adebamowo","doi":"10.3389/fonc.2026.1810950","DOIUrl":"https://doi.org/10.3389/fonc.2026.1810950","url":null,"abstract":"<p><strong>Background: </strong>Self-sampling for HPV testing is increasingly adopted for cervical cancer screening globally, including in Sub-Saharan Africa. However, concerns remain regarding women's willingness and ability to collect samples and the effectiveness of educational interventions. Although prior studies in Africa and Nigeria have examined acceptability and barriers, there is limited evidence on whether structured educational interventions can modify women's attitudes toward HPV self-sampling in routine screening contexts. We evaluated the effect of a structured educational intervention on women's attitudes toward self-sampling and, secondarily, explored baseline correlates of willingness to self-sample among Nigerian women.</p><p><strong>Methods: </strong>We conducted a single-group pre-post quasi-experimental study nested within the African Collaborative Center for Microbiome and Genomics (ACCME) prospective cohort study in central Nigeria. A total of 220 eligible women undergoing cervical cancer screening were enrolled. Baseline measurements were obtained prior to the intervention. The standardized educational intervention, delivered by trained research staff, included brochures, leaflets, an instructional video, verbal instructions, and hands-on familiarization with the Evalyn^® self-sampling brush. Participants subsequently performed self-sampling privately at participating screening facilities. Post-intervention measurements were collected immediately after the educational session and procedure. Samples were analyzed using DEIA/LIPA HPV assays.</p><p><strong>Results: </strong>Most participants were married (63.2%), belonged to the middle socioeconomic group (69.5%), had prior knowledge of cervical cancer (61.8%), and had never undergone screening (89.5%). At baseline, 91.8% were willing to self-sample. The intervention significantly improved mean attitude scores from 42.6 (SD 8.3) to 50.8 (SD 9.8) (p<0.001). Among women unwilling to self-sample, 50.0% (9/18) were in the lower SES group compared with 12.9% (26/202) among willing participants (p<0.001). In exploratory analyses, younger age (OR 0.95, 95% CI 0.90-1.00), cervical cancer knowledge (OR 1.42, 95% CI 1.00-1.99), middle SES (OR 3.69, 95% CI 1.07-12.66), and pre-intervention attitude (OR 0.89, 95% CI 0.81-0.99) were associated with willingness.</p><p><strong>Conclusions: </strong>A structured educational intervention significantly improved attitudes toward HPV self-sampling. Baseline willingness was high, and exploratory analysis indicate that younger age, better knowledge, and middle SES are associated with willingness. These findings support context-specific educational strategies to optimize HPV self-sampling uptake in Nigeria and similar low-resource settings.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1810950"},"PeriodicalIF":3.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835952","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":"A case report: long-term survival cases of nasopharyngeal carcinoma with breast metastasis.","authors":"Xiaojuan Lu, Xingxing Lv, Junyan Wan, Juan Chen, Hong Lu","doi":"10.3389/fonc.2026.1801777","DOIUrl":"https://doi.org/10.3389/fonc.2026.1801777","url":null,"abstract":"<p><strong>Background: </strong>Metastatic malignancies in the breast most commonly originate from cancers of adjacent organs, including lymphoma, melanoma, and lung cancers, while metastases from distant primary sites, including gastrointestinal, head and neck, and pelvic malignancies, are less likely to metastasize to the breast. Nasopharyngeal carcinoma (NPC) with breast metastases is rare. This report describes a patient with pathologically confirmed NPC with breast metastasis who achieved favorable treatment outcomes.</p><p><strong>Case presentation: </strong>A 50-year-old Chinese man with a history of NPC developed multiple systemic metastases. Histopathological examination of a breast lesion confirmed NPC metastasis. After systemic chemotherapy combined with immunotherapy, the patient achieved disease remission and was alive at the time of reporting.</p><p><strong>Conclusion: </strong>This case also serves as a reminder of the importance of re-biopsy for recurrent or metastatic lesions. These observations emphasize the need for further research regarding uncommon metastatic patterns of NPC to refine treatment strategies and improve clinical outcomes.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1801777"},"PeriodicalIF":3.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835965","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":"Correction: Spatial transcriptomics reveals the heterogeneity and FGG+CRP+ inflammatory cancer-associated fibroblasts replace islets in pancreatic ductal adenocarcinoma.","authors":"Zhangyong Ren, Bing Pan, Fangfei Wang, Shaocheng Lyu, Jialei Zhai, Xiumei Hu, Zhe Liu, Lixin Li, Ren Lang, Qiang He, Xin Zhao","doi":"10.3389/fonc.2026.1852367","DOIUrl":"https://doi.org/10.3389/fonc.2026.1852367","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fonc.2023.1112576.].</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1852367"},"PeriodicalIF":3.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835990","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":"Efficacy of traditional Chinese medicine external therapy on cancer-related fatigue: a systematic review and network meta-analysis.","authors":"Xinyu Wang, Shujuan Chen, Fanjiao Meng, Wei Zhou, Yihong Jiang, Jinhong Yang","doi":"10.3389/fonc.2026.1806355","DOIUrl":"https://doi.org/10.3389/fonc.2026.1806355","url":null,"abstract":"<p><strong>Objectives: </strong>The purpose of this network meta-analysis was to compare and evaluate the effectiveness of several traditional Chinese medicine (TCM) external therapies in reducing cancer-related fatigue(CRF).</p><p><strong>Methods: </strong>A search of eight databases was conducted to obtain randomized controlled trials (RCTs) on different external therapies of traditional Chinese medicine for alleviating CRF. The Cochrane ROB 2.0 tool was used to assess the included studies' bias risk. Network meta-analysis and comparative effect ranking were conducted using STATA MP 17.0. The primary outcome was the CRF score. Standardized mean difference (SMD) and 95% confidence interval (95% CI) were used to calculate the effect size. The Confidence in Network Meta-Analysis (CINeMA) tool was used to assess the certainty of the evidence.</p><p><strong>Results: </strong>The systematic review included eighty-seven RCTs covering 13 different external therapies. Among the treatments studied, acupuncture, acupressure, traditional Chinese exercises, transcutaneous acupoint electrical stimulation, moxibustion, Chinese medicine foot bath, traditional Chinese medicine (TCM)emotional care, acupoint injection, acupoint application, warming needle were demonstrated to be effective in alleviating CRF in comparison to usual care. The surface under cumulative ranking curve (SUCRA) indicated that warming needle was most effective in relieving CRF, followed by Chinese medicine foot bath, TCM emotional care, acupoint injections, moxibustion, etc.</p><p><strong>Conclusions: </strong>This review indicated that warming needle might be the most effective traditional Chinese medicine external therapy for treating CRF. But, the low certainty of evidence (assessed via CINeMA) must be emphasized in this low confidence means the results should be interpreted with great caution. Further validation is required through additional clinical trials. These findings provide significant support for future research and clinical trials.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/prospero/, identifier CRD42023479194.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1806355"},"PeriodicalIF":3.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836057","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":"Editorial: Cardiomyopathy and heart failure in oncology.","authors":"Marta Adamiak, Anna Borowiec, Anuradha Kalyanasundaram, Prabhu Mathiyalagan","doi":"10.3389/fonc.2026.1829234","DOIUrl":"https://doi.org/10.3389/fonc.2026.1829234","url":null,"abstract":"","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1829234"},"PeriodicalIF":3.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836082","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":"Personalized swallowing rehabilitation program for post-surgical dysphagia in oral cancer patients: a randomized controlled trial.","authors":"Yanhong Zhang, Hua Chen, Jie Zhou, Nannan Li","doi":"10.3389/fonc.2026.1809479","DOIUrl":"https://doi.org/10.3389/fonc.2026.1809479","url":null,"abstract":"<p><strong>Background: </strong>Dysphagia following oral cancer ablative surgery with free flap reconstruction significantly impairs quality of life, yet personalized rehabilitation approaches remain understudied. This randomized controlled trial compared a personalized swallowing rehabilitation program with standard care in these patients.</p><p><strong>Methods: </strong>This single-center randomized controlled trial enrolled 300 patients with oral squamous cell carcinoma who underwent tumor resection with free flap reconstruction between January 2022 and December 2025 at Shanghai Fengcheng Hospital. Patients were randomly assigned (1:1) to receive either a personalized swallowing rehabilitation program (n=150) incorporating neuromuscular electrical stimulation, surface electromyography biofeedback, tongue pressure resistance training, and individualized exercise protocols, or standard care (n=150) consisting of conventional swallowing exercises. The primary outcome was the Functional Oral Intake Scale (FOIS) score at 6 months. Secondary outcomes included MD Anderson Dysphagia Inventory (MDADI) scores, aspiration rates, time to oral feeding recovery, feeding tube dependency, and aspiration pneumonia incidence, assessed at 1, 3, and 6 months postoperatively.</p><p><strong>Results: </strong>At 6 months, the personalized rehabilitation group demonstrated significantly higher FOIS scores compared with standard care (median, 7 [interquartile range (IQR), 6-7] vs 6 [IQR, 5-6]; Hodges-Lehmann median difference, 1.00; 95% CI, 1.00-1.00; P < 0.001; effect size r = 0.366). The intervention group showed superior MDADI composite scores (median, 75.57 [IQR, 65.99-86.06] vs 65.80 [IQR, 56.30-74.40]; P < 0.001), lower aspiration rates (12.0% vs 21.3%; relative risk, 0.56; P = 0.044), shorter time to oral feeding recovery (median, 15.84 vs 19.80 days; P < 0.001), and reduced feeding tube dependency at 6 months (8.7% vs 28.7%; P < 0.001). Subgroup analyses demonstrated consistent benefits across tumor sites, clinical stages, and reconstruction types, though the effect was attenuated in patients receiving adjuvant chemoradiotherapy (P = 0.201). The mean adherence rate in the intervention group was 78.96% ± 13.34%.</p><p><strong>Conclusions: </strong>A personalized swallowing rehabilitation program significantly improves functional swallowing outcomes, reduces aspiration risk, and enhances swallowing-related quality of life compared with standard care in oral cancer patients following surgical resection with free flap reconstruction. These findings support the integration of individualized, multimodal rehabilitation strategies into routine postoperative management.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1809479"},"PeriodicalIF":3.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836149","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":"Genomic characterization of pulmonary sarcomatoid adenocarcinoma: a paired whole-exome sequencing study of carcinomatous and sarcomatous components.","authors":"Jing Lin, Yuzhong Yang, Mengqing Liu, Fan Yang, Shaofeng Jiang, Longkuan Xu, Xiang Zheng, Hui Wei, Xuyan Wen, Guining Xu, Ruolan Weng, Jinhua Zheng, Shengjun Xiao","doi":"10.3389/fonc.2026.1796428","DOIUrl":"https://doi.org/10.3389/fonc.2026.1796428","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly aggressive subtype of non-small cell lung cancer characterized by the coexistence of carcinomatous (CA) and sarcomatous (SA) components. Their clonal relationship and genomic divergence remain poorly defined, particularly in adenocarcinoma-derived PSC.</p><p><strong>Methods: </strong>We performed comparative whole-exome sequencing (WES) on microdissected CA and SA components from six pulmonary sarcomatoid adenocarcinomas (PSAdC). Histopathology and immunohistochemistry were used to characterize epithelial and mesenchymal phenotypes. Somatic mutations were identified using a standard bioinformatics pipeline, followed by gene set enrichment analysis with g:Profiler.</p><p><strong>Results: </strong>WES identified 133 non-synonymous variants across 34 genes (181 mutational events). Of these, 34.3% were shared, 29.3% were CA-specific, and 36.5% were SA-specific, indicating marked intratumor heterogeneity. Missense mutations predominated (71.4%). Recurrently altered genes included <i>PCLO, CPS1, FAT1, PDE4DIP</i>, and <i>ARID1B</i>, while canonical drivers <i>TP53</i> and <i>KRAS</i> showed component-specific distributions. Enrichment analysis revealed over-representation of pathways related to multicellular organism development, chromatin remodeling, transcription factor binding, and DNA double-strand break repair, as well as non-small cell lung cancer signaling. These alterations correlated with epithelial-mesenchymal transition (EMT) features in SA components, including vimentin upregulation and E-cadherin loss.</p><p><strong>Conclusions: </strong>PSAdC exhibits a monoclonal origin with subsequent genomic diversification between components. Microdissection-based WES reveals pronounced spatial heterogeneity and lineage-specific mutations. Dysregulated chromatin remodeling and DNA repair pathways, together with EMT-associated phenotypes, provide a mechanistic framework for sarcomatoid differentiation and lineage plasticity in this aggressive tumor subtype.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1796428"},"PeriodicalIF":3.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836165","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}