Translational cancer research最新文献

{"title":"Improvement of prognosis among patients with lung adenocarcinoma through precision therapy: analysis based on The Cancer Genome Atlas.","authors":"Ling Gai, Qinfan Wang, Ping Chen, Xiaochun Hou, Liang Ma","doi":"10.21037/tcr-2026-1-0063","DOIUrl":"https://doi.org/10.21037/tcr-2026-1-0063","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is a malignancy with a high global incidence and cancer-related mortality rate. Over decades of development, the treatment of lung cancer has evolved from empirical approaches such as traditional chemotherapy and radiotherapy to a precision model that integrates targeted therapy, immunotherapy, and combination treatments. Through \"molecular profiling and individualized treatment planning\", targeted therapies focusing on biomarkers like EGFR and ALK, along with immunotherapy using programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors, have become landmark achievements in precision medicine for lung cancer. Although various clinical trials have improved the prognosis of LUAD patients, their 5-year survival rate remains low, and precision therapy for lung cancer still faces multiple challenges. This study aims to improve the prognosis of LUAD patients through molecular subtype-based precision treatment.</p><p><strong>Methods: </strong>LUAD RNA-sequencing data sourced from an online database were used to screen for differentially expressed genes (DEGs). Weighted gene coexpression network analysis combined with univariate and multifactorial Cox analysis was used to identify hub prognostic genes. Based on these genes, partitioning around medoids clustering was applied to classify LUAD into two subtypes. The estimation of stromal and immune cells in malignant tumor via using expression data, immunophenoscore, and microenvironment cell populations counter algorithm was used to determine the microenvironmental purity and immune response of the two subtypes. Gene set enrichment analysis was performed to analyze the biological function. The correlation between hub gene and <i>EGFR</i> mutations was detected in clinical samples via immunohistochemical (IHC) staining.</p><p><strong>Results: </strong>This study delineated two distinct subtypes of LUAD, and the survival rate for patients in cluster 2 was found to be significantly superior to that of cluster 1. Additionally, patients in cluster 2 had greater immune cell infiltration, a greater microenvironmental component, and a higher rate of <i>EGFR</i> mutation. In contrast, patients in cluster 1 exhibited a higher degree of fibroblast infiltration and a notable prevalence of <i>NTRK3</i> mutations, as observed in the study of the tumor microenvironment. In addition, functional analysis suggested cluster 1 was associated with nucleotide sequence repair, while cluster 2 was mainly related to lipid metabolism and angiogenic pathways. IHC staining revealed that the expression level of <i>BIRC5</i> was notably downregulated in early-stage patients with <i>EGFR</i>-mutant LUAD. Furthermore, in the advanced stage, the expression level of <i>BIRC5</i> in the tissues of these patients was significantly higher compared to those in patients with the <i>EGFR</i> wild type.</p><p><strong>Conclusions: </strong>Patients in cluster 1 ma","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"209"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676629","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":"Obovatol induces apoptosis in breast cancer by downregulating the PI3K/Akt pathway.","authors":"Ling Zhang, Changyou Wei, Xin Yang, Yuting Ye, Youqin Zeng, Siyu Chen, Jiao Xia, Ping Leng","doi":"10.21037/tcr-2025-1-2627","DOIUrl":"https://doi.org/10.21037/tcr-2025-1-2627","url":null,"abstract":"<p><strong>Background: </strong>Obovatol (Ob), extracted from the bark of Magnolia obovata Thunb., originates from a genus with a well-documented history in East Asian traditional medicine for treating ailments characterized by inflammation and neoplastic-like symptoms. Despite preliminary observations suggesting that Ob exerts anti-tumor effects in various cancers, its specific efficacy and underlying mechanisms of action in breast cancer (BC) remain largely unexplored. This study aimed to investigate the anti-tumor efficacy of Ob against BC and to elucidate its underlying molecular mechanisms.</p><p><strong>Methods: </strong>Cell counting kit-8, Transwell, flow cytometry, and Western blotting (WB) assays were used to examine the effects and functions of Ob on cellular proliferation, invasion, and apoptosis in BC cells (MDA-MB-231 and MDA-MB-468). Bagg Albino/c (BALB/c) nude female mice were applied to evaluate the anti-cancer effects and biosecurity of Ob. Transcriptome sequencing was used to identify the pathway modulated by Ob in BC, and WB assays were then used to validate the key findings.</p><p><strong>Results: </strong>In MDA-MB-231 and MDA-MB-468 cells, Ob decreased the cell viability, exhibiting the half maximal inhibitory concentration (IC₅₀) values for 50.97 and 48.29 µM, respectively. Additionally, by upregulating E-cadherin while downregulating N-cadherin and vimentin, Ob reversed the epithelial-mesenchymal transition, thereby significantly inhibiting the migration and invasion of BC cells. Ob led to mitochondrial apoptosis, as shown by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X protein (Bax) and activated caspase-3 levels. Consistent with the <i>in vitro</i> findings, Ob treatment effectively limited tumor growth in the mouse model, demonstrating considerable biological safety. Importantly, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway has been proven to be a key mechanistic target, as Ob suppressed its activation.</p><p><strong>Conclusions: </strong>By downregulating the PI3K/Akt pathway, Ob reduced cell proliferation and invasion and induced apoptosis in BC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"181"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676792","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":"Targeting LRPPRC lactylation disrupts metabolic-immune crosstalk and restores antitumor immunity in hepatocellular carcinoma.","authors":"Na Li, Qian He, Qi Huang, Yongqing Zhu","doi":"10.21037/tcr-2025-aw-2533","DOIUrl":"https://doi.org/10.21037/tcr-2025-aw-2533","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The Warburg effect drives lactate accumulation in the tumor microenvironment (TME), where it functions as a signaling molecule. Lactate-derived lysine lactylation (Kla) is a novel post-translational modification (PTM) implicated in regulating immune cell function. Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) is overexpressed in hepatocellular carcinoma (HCC) and plays key roles in mitochondrial metabolism and immune evasion. However, whether and how LRPPRC is regulated by lactylation to coordinate metabolic-immune crosstalk in HCC remains unknown. This study aims to investigate the role and mechanism of LRPPRC lactylation in linking tumor glycolysis to macrophage polarization in HCC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Bioinformatics analysis identified lactate metabolism-related genes and hub nodes in HCC datasets. LRPPRC lactylation was detected via immunoprecipitation and western blot using pan-Kla antibody. The specific lactylation site was mapped by prediction database and validated by site-directed mutagenesis (K326R). Functional impacts of LRPPRC-Kla&lt;sup&gt;326&lt;/sup&gt; on HCC cell proliferation, invasion, and glycolysis were assessed using Cell Counting Kit-8 (CCK-8), Transwell, wound-healing, and Seahorse assays. The role of LRPPRC-Kla&lt;sup&gt;326&lt;/sup&gt; in macrophage polarization was examined in bone marrow-derived macrophages (BMDMs) from LRPPRC&lt;sup&gt;WT&lt;/sup&gt; and LRPPRC&lt;sup&gt;K326R&lt;/sup&gt; knock-in mice using flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), and cytokine measurement. An &lt;i&gt;in vivo&lt;/i&gt; tumor admix model co-injecting Lewis lung carcinoma (LLC) cells with polarized BMDMs was used to evaluate tumor growth and immune cell infiltration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;LRPPRC was identified as a hub gene among lactate metabolism-related genes in HCC and was upregulated in tumor tissues, correlating with poor prognosis. LRPPRC undergoes lactylation in a lactate-dependent manner, with K326 being the major modification site. The LRPPRC&lt;sup&gt;K326R&lt;/sup&gt; mutation impaired HCC cell proliferation, invasion, and glycolytic flux. In macrophages, lactylation at LRPPRCK326was required for lactate-induced M2 polarization and glycolytic reprogramming; the K326R mutation skewed polarization towards an M1 phenotype with reduced glycolysis. In the tumor admix model, co-injection of LRPPRC&lt;sup&gt;K326R&lt;/sup&gt; M2 macrophages significantly suppressed tumor growth compared to LRPPRC&lt;sup&gt;WT&lt;/sup&gt; M2 macrophages, which was associated with increased infiltration of activated IFN-γ&lt;sup&gt;+&lt;/sup&gt; CD8&lt;sup&gt;+&lt;/sup&gt; and CD4&lt;sup&gt;+&lt;/sup&gt; T cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Lactate-induced lactylation of LRPPRC at K326 serves as a critical metabolic-immune switch in HCC. It enhances tumor glycolysis and simultaneously drives M2-like macrophage polarization, fostering an immunosuppressive TME conducive to tumor progression. Targeting the LRPPRC-Kla&lt;sup&gt;326&lt;/sup&gt; axis may represent a promising thera","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"148"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676798","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":"Targeting the gut microbiota-metabolite-immune axis in cancer immunotherapy: mechanistic interplay, therapeutic strategies, and translational applications-a narrative review.","authors":"Meng Huang, Yunzhao Chen, Xiaobin Cui","doi":"10.21037/tcr-2025-1992","DOIUrl":"https://doi.org/10.21037/tcr-2025-1992","url":null,"abstract":"<p><strong>Background and objective: </strong>Microbiota and their metabolites form a dynamic regulatory network that modulates the tumor microenvironment (TME) and immune cell functionality, emerging as critical targets in cancer immunotherapy. Despite remarkable advances in immune checkpoint inhibitors (ICIs), clinical efficacy remains limited by primary or acquired resistance in a substantial proportion of patients. Accumulating evidence indicates that the gut microbiota-metabolite-immune axis is a critical determinant of ICI responsiveness, but the underlying molecular mechanisms and tumor-specific regulatory patterns remain incompletely elucidated. This narrative review aims to systematically dissect the mechanistic interplay of this axis across diverse cancer types and synthesize current microbiota-targeted therapeutic strategies for improved immunotherapy outcomes.</p><p><strong>Methods: </strong>We conducted a systematic literature search of PubMed for studies published between January 2019 and December 2025, with a particular focus on basic and translational research elucidating the roles of gut microbiota and their metabolites in cancer immunotherapy across various malignancies.</p><p><strong>Key content and findings: </strong>This review elucidates the molecular mechanisms by which core metabolites regulate antitumor immunity, synthesizes characteristic microbial signatures across gastrointestinal and non-gastrointestinal cancers. Furthermore, we evaluate the translational potential of intervention strategies, including fecal microbiota transplantation, probiotic supplementation, and engineered microbes, as adjuvants to enhance ICI efficacy and overcome resistance.</p><p><strong>Conclusions: </strong>Microbiota-based personalized therapeutic strategies are increasingly recognized as promising tools to modulate antitumor immunity and improve immunotherapy outcomes. Systematic profiling of the gut microbiota-metabolite-immune axis across cancer types will facilitate the development of precision interventions to overcome ICI resistance. Future research integrating multi-omics approaches and large-scale clinical trials is pivotal to translate mechanistic insights into clinically viable therapies, ultimately revolutionizing the landscape of cancer immuno-oncology.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"214"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676820","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":"Cost-effectiveness of cancer screening and overall survival benefit.","authors":"Takeshi Takahashi","doi":"10.21037/tcr-2026-1-0100","DOIUrl":"https://doi.org/10.21037/tcr-2026-1-0100","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"137"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676964","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":"Prognostic value of systemic inflammation indices in patients with metastatic colorectal cancer treated with TAS-102: a single-center retrospective real-world study.","authors":"Ming Liu, Yue Cui, Lili Chen, Feifei Zhang, Fangqi Liu","doi":"10.21037/tcr-2025-aw-2406","DOIUrl":"https://doi.org/10.21037/tcr-2025-aw-2406","url":null,"abstract":"<p><strong>Background: </strong>While the efficacy of trifluridine/tipiracil (TAS-102) in late-line metastatic colorectal cancer (mCRC) is established in clinical trials, real-world predictive and prognostic factors remain poorly characterized. This study aimed to identify these factors in mCRC patients receiving TAS-102 at The Second Affiliated Hospital of Anhui Medical University.</p><p><strong>Methods: </strong>Data were extracted from The Second Affiliated Hospital of Anhui Medical University to evaluate the clinical outcomes of microsatellite stable mCRC patients treated with TAS-102 in late-line between 2019 and 2025. Pan-immune-inflammation value (PIV), systemic immune-inflammation index (SII) values, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) before treatment and other potential risk factors were retrospectively collected. The receiver operating characteristic curves were applied to determine the cut-off values of PIV, SII, NLR, and PLR in patients. The risk factors for progression-free survival (PFS) and overall survival (OS) were compared with Kaplan-Meier curves and determined by univariate and multivariate Cox regression analyses. Factors with P<0.05 in univariate analysis were included in multivariate analysis.</p><p><strong>Results: </strong>A total of 61 mCRC patients were enrolled. In the multivariate analysis of PFS, two favorable indices were significant: Eastern Cooperative Oncology Group Performance Status (ECOG-PS) <2 (P=0.03) and SII <650 (P=0.003). Two independent prognostic factors identified in the multivariate analysis of OS were ECOG-PS <2 (P=0.002) and NLR <2.35 (P=0.03).</p><p><strong>Conclusions: </strong>Our findings demonstrate that pretreatment inflammatory indices (NLR and SII) combined with baseline ECOG-PS independently identify mCRC patients likely to derive clinical benefit from TAS-102 therapy.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"167"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676999","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":"Gene expression profile, and role of baicalein in the inhibition of thyroid cancer.","authors":"Nan Wu, Qian Zhang, Muhammad Naeem, Ren Jing, Yuanbin Luo, Yang Wu, Shijian Yi","doi":"10.21037/tcr-2025-aw-2437","DOIUrl":"https://doi.org/10.21037/tcr-2025-aw-2437","url":null,"abstract":"<p><strong>Background: </strong>Anaplastic thyroid cancer (ATC) is the highly undifferentiated form of thyroid cancer, and its incidence is still high all around the globe. The current treatment for ATC includes surgery, chemotherapy, and radioactive iodine therapy. These treatment options are not reliable due to high cost, drug resistance, and toxicity issues. Baicalein (BA) is a natural flavonoid isolated from <i>Scutellaria baicalensis</i> that exhibits several pharmacological activities, including anticancer, anti-inflammatory, antioxidant, and antitumor. The role of BA in elucidating the mechanism of ATC, emphasizing the CLU-mediated mitophagy, remains unclear. This study was designed to investigate the impact of BA on gene expression and cellular pathways in CAL62 ATC cells by CLU-mediated mitophagy.</p><p><strong>Methods: </strong>Differential gene expression and pathway enrichment were assessed using RNA sequencing and gene set enrichment analysis (GSEA). Mitochondrial fluorescence and mitophagy markers (PINK1, PRKN, ATG5, MFN1) were evaluated by quantitative polymerase chain reaction (qPCR) and fluorescence microscopy. CLU expression and its correlation with cancer progression were analyzed using The Cancer Genome Atlas (TCGA) data.</p><p><strong>Results: </strong>BA treatment altered gene expression and pathway activity, impacting processes including cell proliferation, mitophagy, and epithelial-mesenchymal transition. It reduced the mitochondrial fluorescence intensity and mitophagy marker levels, consistent with an inhibition of mitophagy. BA also modulated thyroid cancer markers, indicating the induced dedifferentiation. TCGA analysis confirmed the CLU upregulation in thyroid cancer, linking it to disease progression and survival. BA inhibits ATC cell growth, an effect associated with the alteration of CLU-linked mitophagy and key signaling pathways.</p><p><strong>Conclusions: </strong>These findings highlight that CLU as a potential therapeutic target and suggested BA as a promising strategy for thyroid cancer intervention.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"163"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677004","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":"UV1 plus pembrolizumab in recurrent and metastatic head and neck squamous cell carcinoma: safe, immunogenic, but lacking efficacy.","authors":"Guillermo Flores, Marisa R Buchakjian, Molly Heft Neal, J Chad Brenner","doi":"10.21037/tcr-2025-1-2689","DOIUrl":"https://doi.org/10.21037/tcr-2025-1-2689","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"140"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677039","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":"RNAscope-based HER2 mRNA detection shows high concordance with fluorescence <i>in situ</i> hybridization in invasive breast carcinoma: a retrospective study.","authors":"Wei Hua, Yunhe Gu, Ying Yuan, Jiyuan Zhu, He Wu","doi":"10.21037/tcr-2025-aw-2486","DOIUrl":"https://doi.org/10.21037/tcr-2025-aw-2486","url":null,"abstract":"<p><strong>Background: </strong>Human epidermal growth factor receptor 2 (HER2) status is critical for guiding targeted therapy in invasive breast cancer (BC). Immunohistochemistry (IHC) is routinely used for HER2 screening, but equivocal (IHC 2+) cases require confirmatory testing. RNAscope is an emerging RNA <i>in situ</i> hybridization technique with proven consistency and sensitivity. We investigated whether RNAscope can reliably determine HER2 status and enhance diagnostic concordance with FISH in IHC 2+ invasive ductal carcinoma (IDC).</p><p><strong>Methods: </strong>In this retrospective study, 104 IDC cases from January 2020 to January 2024 were reviewed. Thirty-five cases with IHC 2+ scores were randomly selected. Each case underwent RNAscope and fluorescence in situ hybridization (FISH) for HER2. Concordance between RNAscope and FISH results was evaluated using Cohen's kappa statistic. Next-generation sequencing (NGS) was performed on discordant cases to confirm HER2 gene status.</p><p><strong>Results: </strong>RNAscope and FISH results were concordant in 85.7% (30/35) of IHC 2+ cases [κ=0.678, 95% confidence interval (CI): 0.425-0.872], indicating substantial agreement. RNAscope detected HER2 positivity in all 12 FISH-positive cases (100% agreement) and in 5 of 23 FISH-negative cases, identifying additional positive cases. Among the 5 discordant cases, NGS confirmed HER2 amplification or overexpression in 4 (80%) of the RNAscope-positive/FISH-negative cases. These findings suggest that RNAscope may detect HER2-positive cases missed by FISH.</p><p><strong>Conclusions: </strong>RNAscope shows high agreement with FISH in determining HER2 status in IHC 2+ IDC. RNAscope may serve as an effective adjunct to current HER2 testing, offering a sensitive alternative for ambiguous cases.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"174"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676365","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":"Identification and validation of a sphingolipid metabolism-related prognostic signature for predicting prognosis and immune microenvironment-related characteristics in ovarian cancer.","authors":"Xin Lian, Hao Chang, Yun Yang, Yichen Guo, Lei Zhang, Xuemei Jia","doi":"10.21037/tcr-2025-aw-2260","DOIUrl":"https://doi.org/10.21037/tcr-2025-aw-2260","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OV) is the leading cause of mortality among gynecological malignancies, often diagnosed at an advanced stage and prone to recurrence after treatment. In order to improve the prognosis, there is an urgent clinical need to identify novel strategies for early intervention and prognosis prediction. Sphingolipids are both important components of cell membranes and closely related to cell signaling. Key enzymes and intermediates of sphingolipid metabolism have critical roles in regulating biological processes such as proliferation and apoptosis of cancer cells, and some of the anticancer drugs targeting sphingolipid metabolism have already entered into clinical trials. However, the prognostic value of sphingolipid metabolism-related genes (SRGs) in OV remains unclear. This study aims to systematically evaluate the prognostic significance of SRGs in OV and construct a prognostic risk model to improve survival prediction.</p><p><strong>Methods: </strong>In this study, we integrated transcriptomic profiles and corresponding clinical data of OV patients from the Cancer Genome Atlas (TCGA; https://portal.gdc.cancer.gov/) and the Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/) databases. Through univariate and multivariate Cox regression analyses, we identified five SRGs to construct a prognostic signature of OV. Based on the signature-derived risk scores, all samples were stratified into high- and low-risk groups. To further evaluate the signature's clinical utility, we comprehensively assessed its associations with immune microenvironment, immunotherapy response and chemotherapy sensitivity. Finally, <i>in vitro</i> experiments were performed to validate the functional role of the key gene <i>CERK</i> in the model.</p><p><strong>Results: </strong>Patients stratified according to risk scores exhibited statistically significant differences in survival outcomes. The robustness and predictive accuracy of this signature were consistently validated in both internal and external cohorts. Comprehensive analysis of the immune microenvironment and immunotherapy response revealed that patients in the low-risk group were more likely to derive clinical benefit from immunotherapy. Moreover, drug sensitivity analysis indicated that the low-risk group was more responsive to olaparib, whereas the high-risk group showed increased sensitivity to Topotecan. Critically, functional experiments demonstrated that CERK knockout in this model significantly suppressed proliferation, migration, and invasion capacities in SKOV3 and ES-2 cell lines.</p><p><strong>Conclusions: </strong>We developed a sphingolipid metabolism-related prognostic signature (SRPS), which demonstrated robust performance in predicting survival outcomes and guiding personalized therapeutic strategies.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"153"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676372","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}