Translational Oncology最新文献

{"title":"Enhancement of Prognostic Outcomes in Stage III Non-Small Cell Lung Cancer: A Retrospective Study on Neoadjuvant Immuno-Chemotherapy Followed by Definitive Chemo-Radiotherapy","authors":"Wenxin Ding ,&nbsp;Yechen Ma ,&nbsp;Hao Hu ,&nbsp;Tian Xu ,&nbsp;Hexin Duan ,&nbsp;Jiang Liang ,&nbsp;Weiwei Liang ,&nbsp;Hao Zhou ,&nbsp;Xi Zhang ,&nbsp;Zewen Song","doi":"10.1016/j.tranon.2025.102394","DOIUrl":"10.1016/j.tranon.2025.102394","url":null,"abstract":"<div><h3>Background</h3><div>The effectiveness of neoadjuvant immuno-chemotherapy in stage III non-small cell lung cancer (NSCLC) patients undergoing definitive concurrent/sequential chemo-radiotherapy (CRT) is not well established.</div></div><div><h3>Methods</h3><div>This retrospective study involved stage III NSCLC patients treated at the Third Xiangya Hospital and Xiangxi Autonomous Prefecture People's Hospital. We compared prognosis, dosimetric outcomes, and radiation pneumonitis incidence between those receiving neoadjuvant immuno-chemotherapy and those undergoing immunotherapy maintenance after CRT. Tumor assessments were conducted on patients administered 2–4 cycles of immuno-chemotherapy, and diagnostic CT images of 54 patients were analyzed for treatment impact.</div></div><div><h3>Results</h3><div>A total of 76 patients received neoadjuvant immuno-chemotherapy followed by CRT, while 68 received immunotherapy after CRT. The median progression-free survival (PFS) for the neoadjuvant group was 29.3 months compared to 13.4 months for the maintenance group (<em>p</em> &lt; 0.001). Median overall survival (OS) was not reached for the neoadjuvant group, while it was 37.4 months for the maintenance group (<em>p</em> = 0.004). Uni-variable analysis indicated neoadjuvant immuno-chemotherapy as an independent OS prognostic factor. The disease control rate was 99.09 %, and significant reductions in tumor volume and radiation doses to healthy tissues were observed post-treatment.</div></div><div><h3>Conclusion</h3><div>Our findings suggest neoadjuvant immuno-chemotherapy improves prognosis for stage III NSCLC patients and effectively reduces tumor volume and organ-at-risk radiation exposure, warranting further phase III trials.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102394"},"PeriodicalIF":5.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of patient-derived xenograft models in Chinese patients with multiple myeloma: Insights into therapeutic responsiveness and molecular subtyping","authors":"Xueju Wang ,&nbsp;Di Zhou ,&nbsp;Chanjuan Jin ,&nbsp;Zhangzhen Shi ,&nbsp;Danyi Wen ,&nbsp;Lintao Bi","doi":"10.1016/j.tranon.2025.102385","DOIUrl":"10.1016/j.tranon.2025.102385","url":null,"abstract":"<div><div>Multiple myeloma (MM), a malignant hematologic tumor characterized by the proliferation of monoclonal plasma cells, remains incurable with high relapse rates despite advances in treatment. Patient-derived xenograft (PDX) models have emerged as a promising tool for understanding MM's complex pathophysiology and testing therapeutic responses. In this study, we successfully developed PDX models from three patients with MM by subcutaneously engrafting their tumor cells into immunodeficient NCG mice. These models accurately mirrored the clinical drug responses of their corresponding patient cases, exhibiting similar drug sensitivities and resistance patterns. Omics profiling facilitated the alignment of PDX models with specific molecular subgroups identified in current MM research, enhancing the models' clinical relevance. The concordance between PDX models and clinical data confirms the utility of these models in simulating patient-specific responses and advancing personalized treatment strategies. This study validates the effectiveness of PDX models established by subcutaneous engraftment of tumor cells in replicating human disease and treatment responses, thus providing a robust platform for future personalized treatments and development of targeted interventions in Chinese MM patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102385"},"PeriodicalIF":5.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N6-methyladenosine binding protein YTHDF2 inhibits gastric cancer cell growth and predicts better prognosis in patients with gastric cancer","authors":"Jun Zheng ,&nbsp;Yinhua Liang ,&nbsp;Xin Xu ,&nbsp;Jianpeng Zhou ,&nbsp;Shuang Jiang ,&nbsp;Jiwei Yu","doi":"10.1016/j.tranon.2025.102395","DOIUrl":"10.1016/j.tranon.2025.102395","url":null,"abstract":"<div><h3>Background</h3><div>The potential role of N6-methyladenosine (m6A) in cancer progression has received significant attention in the past few years. The purpose of this study aimed to evaluate the impact of YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2) on patient prognosis and its potential role in gastric cancer.</div></div><div><h3>Methods</h3><div>A total of 305 patients with clinically informative gastric cancer were identified from The Cancer Genome Atlas (TCGA) dataset, and GSE29272 and GSE84437 were used as external validation. Different m6A modulators were analyzed using the Limma package; the Cox regression models were used to determine risk factors for overall survival (OS). A 1:1 propensity score matching (PSM) analysis was used to adjust for differences in baseline clinicopathological characteristics between the YTHDF2 low and high expression groups. The Cox regression analysis was then used to identify risk factors for OS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to explore the potential role and function of YTHDF2 in gastric cancer. And the effects of YTHDF2 on the growth of gastric cancer cells were detected in vivo and in vitro.</div></div><div><h3>Results</h3><div>Nineteen m6A methylation regulators were expressed in gastric cancer tissues; YTHDF2 was associated with the prognosis of gastric cancer patients. The expression level of YTHDF2, patient age, and tumor stage were independent risk factors for OS. After PSM, YTHDF2 expression led to a relatively better prognosis and staging. Patients in stage IV had a significantly worse prognosis. The expression of YTHDF2 was associated with cancer-related functions and pathways in gastric cancer. We found that YTHDF2 has lower expression in gastric cancer cells and inhibits the growth of GC cells.</div></div><div><h3>Conclusions</h3><div>The high expression of YTHDF2 can predict a better prognosis of gastric cancer patients. YTHDF2 exerts a critical role in gastric cancer progression by inhibiting the growth of GC cells.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102395"},"PeriodicalIF":5.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Raddeanin A exerts potent efficacy against non-small cell lung cancer by inhibiting cyclin-dependent kinase 6","authors":"Xian Wang ,&nbsp;Xiao Lin ,&nbsp;Yuxin Liu ,&nbsp;Chunbo Ma ,&nbsp;Mengchu Liu ,&nbsp;Jiayu Bai ,&nbsp;Yihan Ye ,&nbsp;Chengguang Zhao ,&nbsp;Lehe Yang ,&nbsp;Xiaoying Huang ,&nbsp;Liangxing Wang","doi":"10.1016/j.tranon.2025.102382","DOIUrl":"10.1016/j.tranon.2025.102382","url":null,"abstract":"<div><h3>Purpose</h3><div>The aim of this study was to investigate the anti-tumor effects and mechanisms of Raddeanin A in NSCLC in vitro and in vivo.</div></div><div><h3>Methods</h3><div>The effects of Raddeanin A on cell cycle progression, proliferation, migration and invasion of NSCLC were assessed by flow cytometry and cell biological assays in multiple NSCLC cell lines. To identify possible targets of Raddeanin A in NSCLC, we employed a multifaceted approach incorporating network pharmacology, molecular docking, and molecular dynamics simulation, along with additional techniques such as SPR (Surface Plasmon Resonance), Co-IP (Co-Immunoprecipitation), and immunofluorescence. In vivo effects were investigated using a nude mouse xenograft tumor model.</div></div><div><h3>Results</h3><div>Raddeanin A inhibits NSCLC cell survival, inhibits invasion and migration and causes cell cycle arrest in G1 phase. Raddeanin A impacts NSCLC cellular activity by inhibiting CDK6, leading to anti-tumor effects. Molecular analysis confirms that the tight binding between Raddeanin A and CDK6, facilitated by specific hydrogen bonds at binding sites including VAL-101, HIS-100, GLN-149, LYS-147, THR-182, VAL-180, and ALA-23, stabilizes within the 40–100 ns interval. In a nude mouse xenograft tumor model, Raddeanin A also demonstrated an inhibitory effect on NSCLC tumor growth.</div></div><div><h3>Conclusions</h3><div>Raddeanin A blocks the cell cycle in G1 phase by inhibiting CDK6. Raddeanin A is expected to be a novel antitumor agent against NSCLC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102382"},"PeriodicalIF":5.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CUL4B regulates thyroid cancer differentiation and treatment sensitivity by ubiquitinating ARID1A","authors":"Haiyan Gu ,&nbsp;Bo Han ,&nbsp;Jing Hu ,&nbsp;Ping Liu ,&nbsp;Wenyao Liu ,&nbsp;Ying Qu ,&nbsp;Lin Zhang ,&nbsp;Panpan Li ,&nbsp;Gongzheng Wang ,&nbsp;Zhiyan Liu ,&nbsp;Mei Qi ,&nbsp;Feifei Sun","doi":"10.1016/j.tranon.2025.102389","DOIUrl":"10.1016/j.tranon.2025.102389","url":null,"abstract":"<div><h3>Background</h3><div>Thyroid cancer (TC) is a prevalent endocrine malignancy with a generally favorable prognosis. However, dedifferentiation of TC poses a significant challenge, resulting in poorer patient outcomes and necessitating urgent attention. Cullin 4B (CUL4B), a scaffold protein involved in proteolysis and epigenetic regulation, has been reported to play an oncogenic role in many human malignancies, though its involvement in TC remains unclear.</div></div><div><h3>Methods</h3><div>The association between CUL4B expression and prognosis in TC patients was assessed using immunohistochemistry. RNA-seq was utilized to investigate the underlying molecular mechanisms, which were further validated through <em>in vitro</em> experiments. The target gene of CUL4B was identified, and the complete ubiquitination regulation process was described. The phenomenon of high expression of CUL4B in TC was explained by identifying that CUL4B-mediated regulation of the SWI/SNF complex.</div></div><div><h3>Results</h3><div>Our findings revealed that CUL4B expression was positively correlated with tumor progression and poor prognosis in TC. Mechanistically, overexpression of CUL4B promoted the progression and dedifferentiation of TC <em>in vivo</em> models. Crucially, we discovered that CUL4B drives dedifferentiation by promoting the ubiquitination of ARID1A within SWI/SNF complex, leading to decreased expression of the differentiation marker paired box 8 (PAX8). This loss of PAX8 contributes to the dedifferentiation process, ultimately resulting in the formation of anaplastic thyroid carcinoma (ATC). Moreover, silencing CUL4B increased the sensitivity of TC cells to MAPK inhibitors.</div></div><div><h3>Conclusion</h3><div>CUL4B was crucial in driving tumor advancement and inhibiting differentiation in TC by facilitating the ubiquitin-mediated degradation of ARID1A, underscoring its potential as a therapeutic target.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102389"},"PeriodicalIF":5.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-derived immunoglobulin-like transcript 3 inhibition reshapes the immunosuppressive tumor microenvironment and potentiates programmed cell death ligand 1 blockade immunotherapy in lung adenocarcinoma","authors":"Leirong Wang ,&nbsp;Qing Li ,&nbsp;Yanxin Sun ,&nbsp;Shuyun Wang ,&nbsp;Xuebing Fu ,&nbsp;Xiufen Wang ,&nbsp;Yan Zheng ,&nbsp;Aiqin Gao ,&nbsp;Yuping Sun ,&nbsp;Juan Li","doi":"10.1016/j.tranon.2025.102381","DOIUrl":"10.1016/j.tranon.2025.102381","url":null,"abstract":"<div><div>The low response rate of current immune checkpoint inhibitors in cancer has necessitated the development of new immune targets.</div><div>Survival and public databases analyses were performed to determine the clinical significance of immunoglobulin-like transcript 3 (ILT3). The impact of ILT3 and apolipoprotein E (APOE) on tumor-associated macrophage (TAM) recruitment and polarization were evaluated by transwell assay, flow cytometry (FCM), and real-time PCR, while their impact on T cell survival and cytotoxicity was detected by CFSE, apoptotic assay, FCM and ELISA. These pro-tumoural activity of (an ortholog of ILT3 in mouse) were verified in vivo models.</div><div>Survival and public databases analyses revealed that high ILT3 expression was significantly associated with worse prognosis in lung adenocarcinoma (LUAD), but not in squamous cell carcinoma. The same association was observed with its ligand, APOE. <em>In vitro</em> assays demonstrated that tumor-derived ILT3/APOE promoted recruitment and M2-like polarization of TAMs in LUAD and directly inhibited T cell proliferation and cytotoxicity. <em>In vivo</em> knockdown of gp49b enhanced anti-tumor immunity and suppressed tumor progression by counteracting TAM- and dysfunctional T cell-induced tumor microenvironment immunosuppression. Furthermore, combined inhibition of gp49b and programmed cell death ligand 1 (PD-L1) showed the most drastic tumor regression in C57BL/6 mice models.</div><div>Tumor-derived ILT3 overexpression suppresses anti-tumor immunity by recruiting M2-like TAMs and impairing T cell activities, while ILT3 inhibition counteracts this immunosuppression and enhances the efficacy of PD-L1 blockade in LUAD. Thus, ILT3 could be a promising novel immunotherapeutic target for combined immunotherapy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102381"},"PeriodicalIF":5.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive characterization of T cell subtypes in lung adenocarcinoma: Prognostic, predictive, and therapeutic implications","authors":"Shiquan Liu ,&nbsp;Hao Sun ,&nbsp;Tianye Song ,&nbsp;Ce Liang ,&nbsp;Lele Deng ,&nbsp;Haiyong Zhu ,&nbsp;Fangchao Zhao ,&nbsp;Shujun Li","doi":"10.1016/j.tranon.2025.102332","DOIUrl":"10.1016/j.tranon.2025.102332","url":null,"abstract":"<div><h3>Background</h3><div>T cells are crucial for immunosurveillance and tumor eradication, with their dysregulation or absence in the tumor microenvironment linked to immunotherapy resistance. In lung adenocarcinoma (LUAD), this resistance is a significant barrier to effective treatment, highlighting the need for robust biomarkers and therapeutic targets to improve clinical outcomes.</div></div><div><h3>Methods</h3><div>T cell-related markers were identified through single-cell RNA sequencing analysis. The TCGA dataset was used for consensus clustering to define molecular subtypes associated with distinct survival outcomes and immune profiles. A T cell-related prognostic signature was developed by integrating LUAD datasets from TCGA, GSE31210, GSE50081, and GSE68465 using 10 machine learning algorithms. Further analysis linked risk scores to immune infiltration and drug sensitivity. The role of a hub gene in CD4+ T cell function and its involvement in tumor immunity was explored through in vitro experiments and molecular biology techniques.</div></div><div><h3>Results</h3><div>Cluster analysis identified three LUAD subtypes, with cluster1 showing the best prognosis and immune characteristics. A Lasso + PLSRcox-based signature was a significant risk factor for predicting LUAD patient outcomes, outperforming traditional clinicopathological factors. The risk score correlated with immune microenvironment features, immune cell infiltration, and sensitivity to immunotherapy and chemotherapy. CPA3 expression was elevated in activated CD4+ T cells, particularly in Th1 cells, promoting differentiation and IFN-γ secretion. Overexpression of CPA3 enhanced tumor cell apoptosis and increased Granzyme B and IFN-γ levels, highlighting its role in immune responses.</div></div><div><h3>Conclusion</h3><div>We developed a powerful prognostic signature in LUAD that accurately predicts clinical outcomes and can guide immunotherapy and chemotherapy responses.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102332"},"PeriodicalIF":5.0,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation sequencing in early-stage multiple primary lung cancer: The prognostic significance of genomic accumulation status and BCL2L11del","authors":"Mu-Ting Wang ,&nbsp;Chen-Hui Ni ,&nbsp;Yan-Qi Lu ,&nbsp;Wei Zheng ,&nbsp;Shu-Liang Zhang ,&nbsp;Mao-Hui Chen ,&nbsp;Bin Zheng ,&nbsp;Chun Chen","doi":"10.1016/j.tranon.2025.102383","DOIUrl":"10.1016/j.tranon.2025.102383","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;This study aimed to define the genomic features of tumors and to delineate the potential mutational pattern underlying the prognosis of patients using large-panel next-generation sequencing (NGS) assays. Additionally, the study sought to explore the biological functions and prognostic significance of PRMT8 in BCL2L11&lt;sup&gt;del&lt;/sup&gt; lung cancer.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A total of 53 patients were enrolled, with a total of 130 malignant tumors. Clinical variables were collected, and the NGS sequencing of a large panel of 116 tumor-associated genes was performed. According to the gene mutation series and the number of mutation sites, the patients were divided into a series of groups. We then utilized the TCGA-LUAD database to conduct differential gene expression analysis, KEGG enrichment analysis, GSEA, and prognostic evaluation. Cell experiments (transwell migration assays, wound healing assay, CCK8 assay, and apoptosis assay) were utilized to verify the roles of PRMT8 on A549 cell. Western blotting was used to investigate the effect of PRMT8 on the mTORC1 signaling pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The patients exceeding the IA stage were associated with a significantly shorter DFS than those in the IA stage (mean time: 27.5 vs. 50.6 months, &lt;em&gt;p&lt;/em&gt; = 0.044), and &lt;em&gt;BCL2L11&lt;/em&gt;&lt;sup&gt;del&lt;/sup&gt; subsets were associated with a significantly worse DFS (31.9 vs. 50.2 months, &lt;em&gt;p&lt;/em&gt; = 0.047). In the subgroups, the patients with a single gene mutation series with multiple gene mutation sites had a shorter DFS than those with a single mutation site (37.6 vs. 53.9 months, &lt;em&gt;p&lt;/em&gt; = 0.047); and those with four gene series with over four mutation sites displayed a longer DFS than those with four sites (25.7 vs. 58 months, &lt;em&gt;p&lt;/em&gt; = 0.034). In a Cox Multivariate analysis, exceeding the IA stage and a &lt;em&gt;BCL2L11&lt;/em&gt;&lt;sup&gt;del&lt;/sup&gt; mutation were considered unfavorable independent prognostic factors (HR = 5.102, 95 %CI: 1.526 to 17.054; &lt;em&gt;p&lt;/em&gt; = 0.008, and HR = 6.010, 95 %CI: 1.636 to 22.079; &lt;em&gt;p&lt;/em&gt; = 0.007, respectively). A lower gene mutation series (≤2) was an independent factor for a longer DFS (HR = 0.276, 95 %CI: 0.086 to 0.882; &lt;em&gt;p&lt;/em&gt; = 0.03). Our study found that PRMT8 was upregulated in the BCL2L11&lt;sup&gt;del&lt;/sup&gt; group and associated with increased patient survival. Biological experiments showed that PRMT8 overexpression reduced cell viability, promoted apoptosis, inhibited migration and invasion, and suppressed mTORC1 pathway phosphorylation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The prognosis of patients with early-stage MPLC may potentially be related to the accumulation status of gene mutation series and sites; their driving powers may offset each other. Taken together, the application of genomic profiling may prove to be useful for subdividing and precisely managing patients with MPLC. In addition, high expression of PRMT8 presented as an independent prognostic biomarke","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102383"},"PeriodicalIF":5.0,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The fusion characteristics of RET fusion in pan-cancer among the Chinese population: A comprehensive genomic analysis","authors":"Yi Zhao ,&nbsp;Ruo Du ,&nbsp;Mingcong Chen ,&nbsp;Zhiwei Chen","doi":"10.1016/j.tranon.2025.102384","DOIUrl":"10.1016/j.tranon.2025.102384","url":null,"abstract":"<div><h3>Background</h3><div>RET fusions are significant oncogenic drivers, resulting from chromosomal rearrangements of the RET proto-oncogene with various partner genes. Understanding their structural characteristics is crucial for elucidating oncogenic potential and developing targeted therapies.</div></div><div><h3>Methods</h3><div>This study analyzed 21,023 tumor samples and 3716 peripheral blood samples from a Chinese pan-cancer cohort using DNA or RNA-targeted next-generation sequencing (NGS). 19,668 tissues underwent DNA-based fusion detection and 1355 NSCLC tissues underwent RNA-based fusion detection using a 733-gene panel. ctDNA-based targeted NGS was also performed on blood samples.</div></div><div><h3>Results</h3><div>RET fusions were detected in 1.027 % of tissue samples, predominantly lung and thyroid cancers. Compared to Western populations (87 % in intron 11), Chinese patients show a shift toward the exon 10–11 region, with 30.79 % in intron 10. RET rearrangements were classified into four categories (Simple Reciprocal Inversion, Co-Fusion, Single Fusion-Common, Single Fusion-Rare) with unique mutational profiles and tumor mutational burden scores. RNA-based NGS revealed some DNA-detected rearrangements might not undergo transcription, while Co-Fusion indicated potential simultaneous transcription of multiple RET fusions. An NSCLC patient with KIF5B-RET and ATRNL1-RET co-fusions achieved 15-month progression-free survival on RET-targeted therapy.</div></div><div><h3>Conclusion</h3><div>This study underscores the importance of structural insights for developing targeted therapies against RET fusion-driven cancers and highlights the need for further investigation into complex RET fusion mechanisms to better understand RET-driven oncogenesis.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102384"},"PeriodicalIF":5.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumoral and circulating genomic landscape inform survival differences in colorectal carcinomatosis","authors":"Michael G. White ,&nbsp;Reed I. Ayabe ,&nbsp;Mohammad A. Zeineddine ,&nbsp;Fadl A. Zeineddine ,&nbsp;Abdelrahman M.G. Yousef ,&nbsp;Mahmoud Yousef ,&nbsp;Norman J. Galbraith ,&nbsp;J․Bryan Iorgulescu ,&nbsp;Christopher Scally ,&nbsp;Keith Fournier ,&nbsp;Timothy E. Newhook ,&nbsp;Nancy Y. You ,&nbsp;Jason Willis ,&nbsp;Scott Kopetz ,&nbsp;George J. Chang ,&nbsp;John Paul Shen ,&nbsp;Abhineet Uppal","doi":"10.1016/j.tranon.2025.102379","DOIUrl":"10.1016/j.tranon.2025.102379","url":null,"abstract":"<div><div>Colorectal peritoneal metastases (CPM) are the third most common site of metastatic spread of colorectal cancer and are associated with worse survival than other sites of metastatic disease. In recent years tumoral circulating tumoral DNA (ctDNA) mutational status has been increasingly utilized in clinical decision making for metastatic colorectal cancer patients despite its utility in CPM being poorly understood. Here we describe standard of care performed mutational profiles and associated outcomes for unresectable CPM patients, with a contextual comparison to 160 unresected colorectal liver metastases (CLM) patients. Of 508 patients, 288 (57 %) had CPM alone and 220 (43 %) had CPM with extraperitoneal metastases. Patients with synchronous CPM and CLM had worse overall survival (HR 1.67 [95 %CI 1.26–2.22]). Mutations in ctDNA were noted in 110/145 (75.9 %) of CPM patients, with mutations in <em>KRAS</em> or <em>PIK3CA</em> ctDNA being associated with worse survival. Importantly, the association between tumoral mutational profile and survival differed by site of metastatic disease. The prognostic significance of specific mutations, particularly <em>BRAF</em> and <em>KRAS</em>, differs between patients with CPM and CLM, and supports the distinct biology of these metastatic sites and the importance of tissue and circulating genomic profiling to risk-stratify these patients according to site of metastasis.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102379"},"PeriodicalIF":5.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}