Translational Oncology最新文献

{"title":"Comprehensive multi-omics analysis showed that CDC6 is a potential prognostic and immunotherapy biomarker for multiple cancer types including HCC","authors":"Chenxuan Li ,&nbsp;En-di Zhang ,&nbsp;Rui Yu,&nbsp;Bo Yuan,&nbsp;Yunxin Yang,&nbsp;Zhong Zeng,&nbsp;Hanfei Huang","doi":"10.1016/j.tranon.2025.102314","DOIUrl":"10.1016/j.tranon.2025.102314","url":null,"abstract":"<div><h3>Background</h3><div>Cell division cycle 6 (CDC6) is a member of the AAA+ ATPase family and has chaperone-like activity. Many studies have shown that CDC6 plays an important role in cancer development and progression.</div></div><div><h3>Methods</h3><div>Explored CDC6 mRNA and protein expression in normal human tissues and tumors using TCGA, GTEx, and HPA. The role of CDC6 in cancer was analyzed using multiple web platforms and software, including R, cBioPortal, UALCAN, SangerBox and others. Finally, CCK-8, EdU assays and Transwell assays were used to verify the effects of CDC6 knockdown on HCC cell proliferation, migration, and invasion.</div></div><div><h3>Results</h3><div>CDC6 expression was upregulated in most cancers and was associated with poorer prognosis. RNA methylation may play an important role in CDC6 epigenetic modification. CDC6 was significantly positively associated with CD4+ Th2 cells and MDSC in a variety of tumors. Furthermore, immunomodulatory genes are strongly associated with CDC6 expression in most tumor types. CDC6 has higher predictive value than B. Clonality and TMB, and its expression is significantly positively correlated with TMB/MSI and DNAss/RNAss, and is closely related to cell cycle events. Down-regulation of CDC6 can inhibit proliferation, migration and invasion of HCC cells.</div></div><div><h3>Conclusions</h3><div>CDC6 is associated with the occurrence and progression of multiple cancer types by regulating the cell cycle. It holds promise as a diagnostic and prognostic biomarker for cancer, and offers potential in immunomodulatory and targeted therapies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102314"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143181353","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":"Timp2 loss-of-function mutation and TIMP2 treatment in a murine model of NSCLC: Modulation of immunosuppression and oncogenic signaling","authors":"David Peeney ,&nbsp;Sarvesh Kumar ,&nbsp;Tej Pratap Singh ,&nbsp;Yueqin Liu ,&nbsp;Sandra M. Jensen ,&nbsp;Ananda Chowdhury ,&nbsp;Sasha Coates-Park ,&nbsp;Joshua Rich ,&nbsp;Sadeechya Gurung ,&nbsp;Yu Fan ,&nbsp;Daoud Meerzaman ,&nbsp;William G. Stetler-Stevenson","doi":"10.1016/j.tranon.2025.102309","DOIUrl":"10.1016/j.tranon.2025.102309","url":null,"abstract":"<div><div>Mounting evidence suggests that the tissue inhibitor of metalloproteinases-2 (TIMP2) can reduce tumor burden and metastasis. However, the demonstration of such anti-tumor activity and associated mechanisms using in vivo tumor models is lacking. The effects of a <em>Timp2</em> functional mutation and administration of recombinant TIMP2 were examined in both orthotopic and heterotopic murine models of lung cancer using C57Bl/6 syngeneic Lewis Lung 2-luciferase 2 cells (LL2-Luc2) cells. Mice harboring a functional mutation of TIMP2 (mT2) display markedly increased primary lung tumor growth, increased mortality, enriched vasculature, and enhanced infiltration of pro-tumorigenic, immunosuppressive myeloid cells. Treatment with recombinant TIMP2 reduced primary tumor growth in both mutant and wild-type (wt) mice. Comparison of transcriptional profiles of lung tissues from tumor-free, wt versus mT2 mice reveals only minor changes. However, lung tumor-bearing mice of both genotypes demonstrate significant genotype-dependent changes in gene expression following treatment with TIMP. In tumor-bearing wt mice, TIMP2 treatment reduced the expression of upstream oncogenic mediators, whereas treatment of mT2 mice resulted in an immunomodulatory phenotype. A heterotopic subcutaneous model generating metastatic pulmonary tumors demonstrated that daily administration of recombinant TIMP2 significantly reduces the expression of heat shock proteins, suggesting a reduction of cell-stress responses. In summary, we describe how TIMP2 exerts novel, anti-tumor effects in a murine model of lung cancer and that rTIMP2 treatment supports a normalizing effect on the tumor microenvironment. Our findings show that TIMP2 treatment demonstrates significant potential as an adjuvant in the treatment of NSCLC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102309"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143181351","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 colorectal cancer microenvironment: Preclinical progress in identifying targets for cancer therapy","authors":"Abdo Meyiah ,&nbsp;Faez Iqbal Khan ,&nbsp;Dia Aldeen Alfaki ,&nbsp;Khaled Murshed ,&nbsp;Afsheen Raza ,&nbsp;Eyad Elkord","doi":"10.1016/j.tranon.2025.102307","DOIUrl":"10.1016/j.tranon.2025.102307","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a common cancer with high mortality rates. Despite progress in treatment, it remains an incurable disease for many patients. In CRC, the tumor microenvironment (TME) plays critical roles in tumor growth, progression, patients’ prognosis, and response to treatments. Understanding TME complexities is important for developing effective therapies. <em>In vitro</em> and <em>in vivo</em> preclinical models are critical in understanding the disease, discovering potential targets, and developing effective therapeutics. In this review, we focus on preclinical research studies associated with modulation of the TME in CRC. These models give insights into understanding the role of stroma and immune cell components of the TME in CRC and improve clinical responses, providing insights in novel treatment options. Various studies have focused on targeting the TME in CRC to improve responses to different therapeutic approaches. These include identifying targets for cancer therapies, targeting molecular signaling, and enhancing the efficacy of immunotherapeutic modalities. Furthermore, targeting stromal and angiogenic factors in the TME may provide new therapeutic options. Overall, understanding and targeting the TME in CRC is a promising approach for improving therapeutic outcomes.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102307"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143181906","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":"Machine learning identification of a novel vasculogenic mimicry-related signature and FOXM1’s role in promoting vasculogenic mimicry in clear cell renal cell carcinoma","authors":"Chao Xu ,&nbsp;Sujing Zhang ,&nbsp;Jingwei Lv ,&nbsp;Yilong Cao ,&nbsp;Yao Chen ,&nbsp;Hao Sun ,&nbsp;Shengtao Dai ,&nbsp;Bowei Zhang ,&nbsp;Meng Zhu ,&nbsp;Yuepeng Liu ,&nbsp;Junfei Gu","doi":"10.1016/j.tranon.2025.102312","DOIUrl":"10.1016/j.tranon.2025.102312","url":null,"abstract":"<div><h3>Background</h3><div>Clear Cell Renal Cell Carcinoma (ccRCC), the predominant subtype of renal cell carcinoma (RCC), ranks among the most common malignancies worldwide. Vasculogenic mimicry (VM) plays a pivotal role in tumor progression, being closely linked with heightened chemoresistance and adverse prognosis in cancer patients. Nonetheless, the broader impact of vasculogenic mimicry-related genes (VRGs) on ccRCC patient prognosis, tumor microenvironment characteristics, and treatment response remains incompletely understood.</div></div><div><h3>Methods</h3><div>Consensus clustering identified VRG-associated subtypes. We developed a machine learning framework integrating 12 algorithms to establish a consistent VM-related signature (VRG_score). The predictive value of VRG_score for ccRCC prognosis and treatment response was assessed. FOXM1′s clinical relevance was explored using the UCLCAN database. FOXM1 expression in tumor and adjacent tissues was assessed using Western Blotting, IHC, RNA-seq, and Chip-qPCR methods, and its regulatory mechanism was confirmed.</div></div><div><h3>Results</h3><div>We examined VRG mutation and expression patterns in ccRCC at the gene level, identifying two distinct molecular clusters. A consensus VRG_score was formulated using a machine learning computational framework and Cox regression, displaying strong predictive power for prognosis and clinical translation. Additionally, FOXM1 was found to be upregulated in ccRCC, correlating with clinical pathological features and positively regulating PYCR1, thereby activating the PI3K/AKT/mTOR signaling pathway and promoting VM formation.</div></div><div><h3>Conclusion</h3><div>This study constructed a VM-related signature and revealed that FOXM1 promotes VM formation in renal cell carcinoma through the PYCR1-PI3K/AKT/mTOR signaling axis, serving as a prognostic indicator and potential therapeutic target.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102312"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143181349","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":"Efficacy of first-line chemotherapy combined with immunotherapy or anti-angiogenic therapy in advanced KRAS-mutant non-small cell lung cancer","authors":"Huiping Qiang ,&nbsp;Yue Wang ,&nbsp;Yao Zhang ,&nbsp;Jingwen Li,&nbsp;Lincheng Zhang,&nbsp;Huawei Du,&nbsp;Xuxinyi Ling,&nbsp;Shuhui Cao,&nbsp;Yan Zhou,&nbsp;Runbo Zhong,&nbsp;Hua Zhong","doi":"10.1016/j.tranon.2025.102317","DOIUrl":"10.1016/j.tranon.2025.102317","url":null,"abstract":"<div><h3>Background</h3><div>Approximately 30 % non-small cell lung cancer (NSCLC) patients carry <em>KRAS</em> mutations in western countries. First-line chemotherapy combined with immunotherapy has been the standard therapeutic regimen for <em>KRAS</em>-mutant NSCLC patients. This population could also benefit from chemotherapy combined with anti-angiogenic therapy. However, few studies has reported on head-to-head efficacy comparisons between these two treatment strategies.</div></div><div><h3>Methods</h3><div>We selected stage IV <em>KRAS</em>-mutated NSCLC patients diagnosed from 2017 to 2022. Their clinical baseline characteristics, first-line treatment strategy, whether combined <em>TP53</em> or <em>STK11</em> mutation, PD-L1 expression level, etc. were evaluated. The correlation between these factors and progression-free survival (PFS) and overall survival (OS) were analyzed.</div></div><div><h3>Results</h3><div>A total of 273 patients received first-line systematic therapy. The most common mutation was KRAS G12C (34.3 %). First-line chemotherapy combined with immunotherapy brought significant survival benefits (mPFS: 11.0 months vs. 4.0 months, <em>P</em> = 0.0003; mOS: 17.0 months vs. 9.0 months, <em>P</em> = 0.0002) compared with first-line chemotherapy combined with anti-angiogenic therapy. Among the 203 patients who received first-line chemotherapy combined with immunotherapy, PD-L1 positive NSCLC patients responded better than PD-L1 negative patients (mPFS: 11.0 months vs. 4.0 months, <em>P</em> = 0.0004; mOS: 21.0 months vs. 11.0 months, <em>P</em> = 0.0005). ECOG PS score of 0–1 (HR=0.201, <em>P</em> = 0.001) and first-line chemotherapy combined with immunotherapy (HR=0.333, <em>P</em> = 0.009) were independent predictors of OS.</div></div><div><h3>Conclusions</h3><div>Compared with first-line chemotherapy combined with anti-angiogenic therapy, first-line chemotherapy combined with immunotherapy has brought significant survival benefit to advanced <em>KRAS</em> mutant NSCLC patients, especially for PD-L1 positive patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102317"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143181350","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":"ANGPTL3 overcomes sorafenib resistance via suppression of SNAI1 and CPT1A in liver cancer","authors":"Yang-Hsiang Lin ,&nbsp;Cheng-Yi Chen ,&nbsp;Hsiang-Cheng Chi ,&nbsp;Meng-Han Wu ,&nbsp;Ming-Wei Lai ,&nbsp;Chau-Ting Yeh","doi":"10.1016/j.tranon.2024.102250","DOIUrl":"10.1016/j.tranon.2024.102250","url":null,"abstract":"<div><div>Liver cancer, encompassing hepatocellular carcinoma (HCC) and hepatoblastoma, the latter of which primarily occurs in early childhood, is the most common malignant tumor arising from liver and is responsible for a significant number of cancer-related deaths worldwide. Targeted drugs have been used for anti-liver cancer treatment in the advanced stage, while their efficacy is greatly compromised by development of drug resistance. Drug resistance is a complicated process regulated by intrinsic and extrinsic signals and has been associated with poorer prognosis in cancer patients. In the current study, online available dataset analysis uncovered that angiopoietin-like protein 3 (ANGPTL3) manifested lower expression in sorafenib-resistant liver cancer cell lines. Additionally, ANGPTL3 was downregulated in HCC tissues, with its expression positively correlated with good prognosis. Functionally, ectopic expression of ANGPTL3 re-sensitized sorafenib-resistant cells, enhancing the sorafenib-induced reduction in cell viability and migration by suppressing zinc finger protein SNAI1 (SNAI1) expression and the protein stability of carnitine O-palmitoyltransferase 1, liver isoform (CPT1A). Clinical correlation analysis revealed that ANGPTL3 was negatively associated with SNAI1 expression. In conclusion, we identify a novel association between <em>ANGPTL3, SNAI1</em> and <em>CPT1A</em> on sorafenib therapeutic response. Targeting ANGPTL3/SNAI1/CPT1A axis may serve as a therapeutic approach to improve prognosis of liver cancer patients with sorafenib resistance.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102250"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872836","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":"Exogenous dihomo-γ-linolenic acid triggers ferroptosis via ACSL4-mediated lipid metabolic reprogramming in acute myeloid leukemia cells","authors":"Xiandong Jiang ,&nbsp;Yingying Huang ,&nbsp;Xiaoying Hong ,&nbsp;Wei Wu ,&nbsp;Yanfeng Lin ,&nbsp;Liping Lin ,&nbsp;Yan Xue ,&nbsp;Donghong Lin","doi":"10.1016/j.tranon.2024.102227","DOIUrl":"10.1016/j.tranon.2024.102227","url":null,"abstract":"<div><div>Ferroptosis is a novel type of programmed cell death caused by excessive iron-dependent lipid peroxidation. According to various studies, there may be a link between ferroptosis and lipid metabolism. However, few studies have been reported on the lipid metabolism of ferroptosis in acute myeloid leukemia (AML). Here, we analyzed the relationship between lipid metabolism and ferroptosis in AML cells to explore new clinical treatment strategies. This study found that 12 fatty acids were significantly changed in acute myeloid leukemia cell ferroptosis, including dihomo-γ-linolenic acid (DGLA), arachidonic acid (AA), docosahexaenoic acid (DHA), etc. Exogenous DGLA substantially increases the sensitivity to ferroptosis and induces ferroptosis alone in AML cells. In addition, acyl-CoA synthetase long-chain family member 4 (ACSL4) knockout significantly inhibited DGLA-induced AML cells ferroptosis, and ACSL4 regulates DGLA-associated lipid synthesis to affect the sensitivity of AML cells to ferroptosis. Collectively, our studies indicate that a DGLA-enriched diet significantly restricted the growth of leukemia cells as well as induced ferroptosis in vivo.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102227"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792431","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":"UGCG promotes chemoresistance and breast cancer progression via NF-κB and Wnt/β-catenin pathway activation","authors":"Li Long ,&nbsp;Lei Wang ,&nbsp;Yiran Liang ,&nbsp;Fangzhou Ye ,&nbsp;Yuhan Jin ,&nbsp;Dan Luo ,&nbsp;Xiaoyan Li ,&nbsp;Yajie Wang ,&nbsp;Yaming Li ,&nbsp;Dianwen Han ,&nbsp;Bing Chen ,&nbsp;Wenjing Zhao ,&nbsp;Lijuan Wang ,&nbsp;Qifeng Yang","doi":"10.1016/j.tranon.2024.102241","DOIUrl":"10.1016/j.tranon.2024.102241","url":null,"abstract":"<div><h3>Background</h3><div>Taxane-based chemotherapy is the primary treatment for triple-negative breast cancer (TNBC), yet clinical outcomes remain unsatisfactory due to the persistence of chemoresistance. Identifying key factors that contribute to chemoresistance and understanding the associated molecular mechanisms is therefore essential.</div></div><div><h3>Method</h3><div>The GEO databases were utilized to pinpoint factors related to chemoresistance, which were subsequently validated using clinical tissue samples. The role of UGCG in the malignant progression and chemoresistance of TNBC was assessed through various functional assays. Western blotting, qRT-PCR, and immunohistochemistry were employed to investigate the signaling pathways associated with UGCG in TNBC.</div></div><div><h3>Results</h3><div>UGCG expression was notably elevated in chemoresistant breast cancer tissues and cells, as identified in GEO databases and confirmed through immunohistochemistry. Additionally, findings from our cohorts indicated that higher levels of UGCG expression correlated with a lower rate of pathological complete response (pCR), suggesting it could serve as an independent predictor of chemotherapy effectiveness. Gain- and loss-of-function experiments demonstrated that UGCG enhanced the proliferation, metastasis, and stemness of breast cancer cells. Furthermore, treatment with paclitaxel or docetaxel resulted in increased UGCG expression, which in turn reduced chemotherapy-induced cell apoptosis and improved drug resistance and metastatic capabilities. Mechanistically, UGCG was found to amplify the activation of NF-κB and Wnt/β-catenin pathways, and the use of inhibitors targeting these pathways diminished the UGCG-induced malignant effects.</div></div><div><h3>Conclusion</h3><div>Our findings underscore the significant role of UGCG in the chemoresistance and progression of breast cancer, suggesting it as a predictive biomarker and potential therapeutic target to combat chemoresistance in this disease.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102241"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824432","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":"Prognostic implications of immune classification based on PD-L1 expression and tumor-infiltrating lymphocytes in endocervical adenocarcinoma","authors":"Li-Jun Wei ,&nbsp;Zi-Yun Wu ,&nbsp;Li-Yan Wu ,&nbsp;Ying-Wen Wu ,&nbsp;Hao-Yu Liang ,&nbsp;Rong-Zhen Luo ,&nbsp;Li-Li Liu","doi":"10.1016/j.tranon.2024.102265","DOIUrl":"10.1016/j.tranon.2024.102265","url":null,"abstract":"<div><h3>Background</h3><div>Endocervical adenocarcinoma (ECA) comprises a heterogeneous group of diseases whose incidence has increased significantly in recent decades. ECA can be histologically classified into human papillomavirus-associated (HPVA) and non-HPVA (NHPVA) types. Given the variability in pathological features and clinical behavior between the subtypes, evaluating their respective immune microenvironments is essential. They can be categorized into distinct tumor microenvironment immune types (TMIT).</div></div><div><h3>Methods</h3><div>A total of 540 surgically resected ECA samples were classified into HPVA and NHPVA subgroups. Tumor-infiltrating immune markers were assessed using immunohistochemistry. We categorized ECA into four TMIT based on PD-L1 and CD8+ tumor-infiltrating lymphocytes (TILs) expression, and analyzed their prognostic significance.</div></div><div><h3>Results</h3><div>PD-L1 positivity was observed in 319 out of 464 (68.8%) HPVA and 55 out of 76 (72.4%) NHPVA. Across the entire cohort, high CD8+ TILs expression was significantly associated with improved disease-free survival (DFS, <em>p</em>=0.018) and overall survival (OS, <em>p</em>=0.031). A total of 177 samples (32.8%) were classified as TMIT I (high PD-L1 and high CD8+ TILs), exhibiting markedly denser immune cell infiltration compared to the other TMIT groups. In NHPVA subgroup, TMIT was significantly associated with both DFS (<em>p</em>=0.005) and OS (<em>p</em>=0.003). Multivariate analysis identified TMIT as an independent prognostic factor for DFS in the NHPVA group, with TMIT I indicating a more favorable prognosis (<em>p</em>=0.042).</div></div><div><h3>Conclusions</h3><div>TMIT I group within the NHPVA population is most likely to benefit from PD-L1/PD-1 blockade immunotherapies. The immune classification of ECA demonstrates significant prognostic value, suggesting its potential utility in guiding clinical stratification and therapeutic decision-making.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102265"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907668","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":"Composition analysis and mechanism of Guizhi Fuling capsule in anti-cisplatin-resistant ovarian cancer","authors":"Lei Dou ,&nbsp;Yan Yan ,&nbsp;Enting Lu ,&nbsp;Fangmei Li ,&nbsp;Dongli Tian ,&nbsp;Lei Deng ,&nbsp;Xue Zhang ,&nbsp;Rongjin Zhang ,&nbsp;Yin Li ,&nbsp;Yi Zhang ,&nbsp;Ye Sun","doi":"10.1016/j.tranon.2024.102244","DOIUrl":"10.1016/j.tranon.2024.102244","url":null,"abstract":"<div><div>Objective: Cisplatin is the main chemotherapy drug for advanced ovarian cancer, but drug resistance often occurs. The aim of this study is to explore the molecular mechanism by which Guizhi Fuling capsule inhibits cisplatin resistance in ovarian cancer. Methods: First, differences in cisplatin resistance, PA2G4 gene expression, migration, and invasion in A2780 cells and A2780/DDP cells were analyzed by qRT-PCR, scratch assay, transwell, immunofluorescence, and western blotting. Then, LC-MS/MS analysis of GFC chemical composition. qRT-PCR, scratch tests, transwell, pseudopodium formation, immunofluorescence, and western blotting were used to explore the mechanism by which GFC inhibited A2780/DDP cell migration and invasion. Finally, the anti-tumor efficacy of GFC was verified by in vivo experiments. Results: A2780/DDP cells had a greater ability to migrate and invade compared to their parents. Cell viability experiments showed that the migration and invasion ability of A278/DDP cells were significantly inhibited with the increase of GFC concentration. qRT-PCR results showed that compared with the blank control group, cisplatin group and GFC group, the transcription level of PA2G4 gene in the combination treatment group was significantly reduced. We also found that GFC combined with cisplatin inhibited the PI3K/AKT/GSK-3β signaling pathway by targeting PA2G4 gene expression, inhibited the epithelial-mesenchymal transition signaling pathway, decreased cell adhesion and inhibited the formation of cell pseudopodias. Conclusion: GFC combined with cisplatin can target PA2G4 gene to regulate PI3K/AKT/GSK-3β Signaling pathway, inhibiting the invasion and migration of cisplatin resistant A2780/DDP cells in ovarian cancer.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102244"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814283","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}