Translational Oncology最新文献

{"title":"SPC25 upregulates CCND1 to promote the progression of esophageal squamous cell carcinoma by inhibiting MDM2-mediated E2F1 ubiquitination","authors":"Haoyao Jiang ,&nbsp;Xiangfeng Jin ,&nbsp;Haiyong Gu ,&nbsp;Bin Li ,&nbsp;Zhigang Li ,&nbsp;Yifeng Sun","doi":"10.1016/j.tranon.2025.102300","DOIUrl":"10.1016/j.tranon.2025.102300","url":null,"abstract":"<div><div>Esophageal squamous cell carcinoma (ESCC) is highly malignant worldwide. Despite significant advances in the treatment of ESCC, the prognosis remains unfavourable, necessitating research into its mechanisms and treatments. Spindle component 25 (SPC25) can ensure the fidelity of mitotic progression and the accurate segregation of chromosomes, thus plays an important role in the development of malignant tumors, but its role in ESCC is yet to be determined. In this study, the expression of SPC25 was assessed by IHC in 88 primary ESCC samples, with its expression being correlated with advanced clinical features. The function of SPC25 in the proliferation, migration and tumorigenicity of ESCC cells was verified in vitro and in vivo. Mechanistically, SPC25 facilitated tumorigenesis through promoting CCND1 expression. As the transcription factor for CCND1, E2F1 is stabilized by SPC25 through binding the ubiquitin ligase MDM2, resulting in enhanced E2F1 expression, which in turn promotes the expression of CCND1. In addition, overexpression of CCND1 counteracted the effects of SPC25 silencing. Collectively, we demonstrated that the aberrant expression of SPC25 inhibited E2F1 ubiquitination and promoted CCND1 expression, thus accelerating the progression of ESCC. These findings propose novel insights into the role of SPC25 in ESCC and provide potential therapeutic strategies for targeting SPC25 in ESCC patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102300"},"PeriodicalIF":5.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143196695","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":"Molecular effects of clinically relevant chemotherapeutic agents on choline phospholipid metabolism in triple negative breast cancer cells","authors":"Caitlin M. Tressler ,&nbsp;Kanchan Sonkar ,&nbsp;Menglin Cheng ,&nbsp;Vinay Ayyappan ,&nbsp;Ruoqing Cai ,&nbsp;Kristine Glunde","doi":"10.1016/j.tranon.2025.102311","DOIUrl":"10.1016/j.tranon.2025.102311","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is the most lethal breast cancer subtype, leading to poor patient outcomes despite aggressive treatment with surgery, radiation, and chemotherapy. There are currently no clinical tests available which measure early on whether TNBC patients respond to the selected chemotherapy treatment regimen. The magnetic resonance spectroscopy (MRS)-detected total choline (tCho) signal was shown to be a promising biomarker for assessing the response to chemotherapy treatment early on, as breast tumor tCho decreases after the first treatment cycle in patients who respond to chemotherapy cocktails. We sought to further investigate these clinical observations at the molecular level by combining metabolic and transcriptomic studies in two human TNBC cell lines treated with six different chemotherapeutic agents. Overall, our findings show that the glycerophosphocholine-to-phosphocholine ratio (GPC/PC) was a more sensitive and more broadly applicable measure of TNBC response to various chemotherapeutic agents than tCho. Specific chemotherapeutic drugs, including 5-fluorouracil and melphalan, resulted in the most significant effects on choline phospholipid metabolism, while other drugs did not significantly alter choline phospholipid metabolism. Overall, several of the six tested chemotherapeutic drugs mainly affected the expression levels of phosphatidylcholine (PtdC)-specific phospholipases and lysophospholipases, leading to the observed GPC/PC and tCho changes following treatment with the chemotherapeutic agents that altered choline phospholipid metabolism. The presented metabolic and transcriptomic findings support that the GPC/PC ratio and PtdC-phospholipases and -lysophospholipases could be further developed for assessing the response to chemotherapy treatment in TNBC patients.</div><div>Statement of Significance: We show that the glycerophosphocholine-to-phosphocholine ratio and phosphatidylcholine-specific-phospholipases and -lysophospholipases are reliable markers for assessing the response to several chemotherapeutic agents, which could help with selecting correct treatments for TNBC patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102311"},"PeriodicalIF":5.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143196697","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":"Currents status of radiotracers for breast cancer imaging in PET","authors":"Chloé Jean ,&nbsp;Stéphane Roux ,&nbsp;Abdelilah Aziz ,&nbsp;Maxence Mocquery-corre ,&nbsp;Rana Bazzi ,&nbsp;Yacine Merrouche ,&nbsp;Stéphane Dedieu ,&nbsp;Nicolas Etique ,&nbsp;Dimitri Papathanassiou ,&nbsp;Jérôme Devy","doi":"10.1016/j.tranon.2025.102304","DOIUrl":"10.1016/j.tranon.2025.102304","url":null,"abstract":"<div><div>Radiolabeled molecules have become valuable tools in the diagnosis, monitoring, and treatment of cancer, particularly breast cancer. Through the use of radiotracers, clinicians can target specific tumor cells, assess microenvironments, and identify metastases. These radiopharmaceuticals, based on radionuclides, enable both imaging and therapeutic applications, leading to personalized cancer treatment. Techniques such as PET, SPECT, and the use of nanoparticles for theranostics are at the forefront of innovation, offering improved precision in both diagnosis and therapy. This review explores the various ways in which radiotracers are leveraged in modern oncology, with a focus on breast cancer, and highlights recent advancements in targeted radionuclide therapy and nanoparticle-based applications.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102304"},"PeriodicalIF":5.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143196696","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":"Malignant phyllodes tumors with sarcomatous components: A histopathologic and molecular study","authors":"Ting Lei ,&nbsp;Yunjie Song ,&nbsp;Zhiyi Shen ,&nbsp;Yongqiang Shi ,&nbsp;Cunyan Xia ,&nbsp;Xu Deng ,&nbsp;Wenyue Da ,&nbsp;Yan Peng ,&nbsp;Qing Li","doi":"10.1016/j.tranon.2025.102318","DOIUrl":"10.1016/j.tranon.2025.102318","url":null,"abstract":"<div><h3>Background</h3><div>Malignant phyllodes tumors (MPTs) with sarcomatous components are often associated with substantial risks for local and distant recurrences. A more comprehensive characterization of their clinicopathological features and molecular profiles may offer significant potential innovative therapeutic strategies.</div></div><div><h3>Methods</h3><div>A total of ten cases were collected with eight cases undergoing DNA next-generation sequencing (NGS). The clinicopathological characteristics, prognostic information, and genomic profiles were compared to those of MPTs without sarcomatous components.</div></div><div><h3>Results</h3><div>Compared to MPT without sarcomatous components, no significant differences were found in age, tumor position, tumor size, menopausal status, or presence of fibroadenoma (<em>p</em> &gt; 0.05). MPTs with osteosarcoma components had a poor prognosis either compared with other sarcomatous components (<em>p</em> = 0.027) or MPTs without sarcomatous components (<em>p</em> = 0.033). A notably high frequency of mutations was observed in several key genes within MPTs exhibiting sarcomatous components: <em>TP53</em> (<em>n</em> = 6, 75.0 %), <em>MUC16</em> (<em>n</em> = 4, 50.0 %), <em>PTCH1</em> (<em>n</em> = 3, 37.5 %), and <em>APC</em> (<em>n</em> = 3, 37.5 %). In MPTs characterized by sarcomatous components, <em>MCL1</em> (<em>n</em> = 6, 75.0 %) and <em>MYC</em> (<em>n</em> = 5, 62.5 %) demonstrated a notably high frequency of amplification. The NOTCH signaling pathway was significantly associated with MPTs characterized by sarcomatous components (13.6 % vs 75.0 %, <em>p</em> = 0.001).</div></div><div><h3>Conclusions</h3><div>The presence of an osteosarcoma component may serve as an indicator for unfavorable prognosis. Activating mutations in <em>TP53</em> have been identified in these tumors. Furthermore, it typically facilitates tumor formation and progression via the NOTCH signaling pathway. These findings may offer valuable insights for clinical prognosis and identify potential therapeutic targets.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102318"},"PeriodicalIF":5.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349153","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":"Multi-omic and machine learning analysis of mitochondrial RNA modification genes in lung adenocarcinoma for prognostic and therapeutic implications","authors":"Xiao Zhang ,&nbsp;Jiatao Liu ,&nbsp;Yaolin Cao ,&nbsp;Wei Wang,&nbsp;Haoran Lin,&nbsp;Yue Yu","doi":"10.1016/j.tranon.2025.102306","DOIUrl":"10.1016/j.tranon.2025.102306","url":null,"abstract":"<div><div>Lung cancer remains the leading cause of cancer-related deaths, driven by complex pathogenesis and poor prognosis. Recognizing the pivotal role of mitochondrial RNA modifications (MRM) in cancer progression, this study aims to provide a comprehensive analysis of MRM-related genes and their clinical relevance in lung adenocarcinoma (LUAD). Integrating multi-omic datasets, we systematically explored the molecular features of MRM-related genes across various cancers and identified distinct expression patterns and prognostic associations. Single-cell analysis further reveals MRM-driven cell-cell interactions and pathway activation, particularly in cycling and epithelial cells. Using advanced machine learning techniques, we developed a novel prognostic signature—the Mitochondrial RNA Modification-related Signature (MRMS)—comprising nine genes: TXN, LDHA, HMGA1, SFTPB, KRT8, ALG3, S100A16, HSPD1, and ALDOA. The MRMS demonstrates superior predictive performance for LUAD survival compared to previously reported models. Our findings uniquely link MRMS to increased tumor mutational burden, genetic instability, and an immunosuppressive tumor microenvironment characterized by reduced immune cell infiltration and elevated tumor purity. Additionally, MRMS is associated with immunotherapy-related features, suggesting its potential in predicting treatment response. Experimental validation identified ALG3 as an oncogenic driver in LUAD, influencing tumor cell proliferation, migration, and invasion. In conclusion, this study establishes MRMS as a robust prognostic biomarker and highlights its dual role in shaping the tumor immune microenvironment and guiding therapeutic strategies. These findings provide novel insights into mitochondrial RNA modifications and their potential applications in personalized treatment for LUAD.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102306"},"PeriodicalIF":5.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143181907","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":"Comparison of prognosis for T4b rectal cancer with different pelvic compartment involvement treated using neoadjuvant chemoradiotherapy and implications for refinement of the current T staging system: A retrospective cohort study","authors":"Yang-zi Zhang ,&nbsp;Maxiaowei Song ,&nbsp;Shuai Li ,&nbsp;Jian Tie ,&nbsp;Xiang-gao Zhu ,&nbsp;Yong-heng Li ,&nbsp;Ai-wen Wu ,&nbsp;Yong Cai ,&nbsp;Wei-hu Wang","doi":"10.1016/j.tranon.2025.102313","DOIUrl":"10.1016/j.tranon.2025.102313","url":null,"abstract":"<div><h3>Purpose</h3><div>Although classified as one stage, T4b rectal cancer actually represents a group of heterogeneous diseases. Our study aimed to assess the prognosis difference of T4b rectal cancer involving inferior pelvic and other pelvic compartments. This information may be helpful in refinement of the current T staging system.</div></div><div><h3>Methods</h3><div>We retrospectively analysed data from 195 patients with magnetic resonance imaging-identified locally advanced T4b rectal cancer who received neoadjuvant chemoradiotherapy between January 2010 and December 2019. 104 patients had only inferior pelvic compartment involvement (group A) while 91 patients had anterior, posterior or lateral pelvic compartment involvement (group B). Short-term and long-term outcomes were compared between the two groups.</div></div><div><h3>Results</h3><div>After neoadjuvant therapy, 80.8 % patients (84/104) in group A and 92.3 % patients (84/91) in group B underwent surgery. The R0 resection rates were 97.6 % and 89.3 %, respectively. 8.7 % patients (9/104) in group A achieved clinical complete response and adopted watch-and-wait strategy. Patients in group A had significantly superior 5-year progression-free survival (PFS) (67.8 % vs. 55.5 %, <em>P</em> = 0.032) and overall survival (OS) (89.6 % vs. 71.8 %, <em>P</em> = 0.001) than group B. Multivariable Cox regression analysis also identified pelvic compartment involvement classification as an independent predictor of PFS (hazard ratio 1.776, <em>P</em> = 0.046) and OS (hazard ratio 3.477, <em>P</em> = 0.004).</div></div><div><h3>Conclusion</h3><div>T4b rectal cancers with involvement limited to the inferior pelvic compartment had superior prognosis compared to those involving other pelvic compartments. These differences should be investigated further and taken into consideration in refinement of the current T staging system.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102313"},"PeriodicalIF":5.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143182250","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":"Studying breast cancer lung metastasis using a multi-compartment microfluidic device with a mimetic tumor-stroma interaction model","authors":"Bahareh Zarin ,&nbsp;Laleh Rafiee ,&nbsp;Sorosh Abdollahi ,&nbsp;Maryam Vatani ,&nbsp;Mohsen Hassani ,&nbsp;Amir Sanati-Nezhad ,&nbsp;Shaghayegh Haghjooy Javanmard","doi":"10.1016/j.tranon.2025.102303","DOIUrl":"10.1016/j.tranon.2025.102303","url":null,"abstract":"<div><h3>Background</h3><div>Understanding the mechanisms underlying the metastasis of breast cancer cells to the lungs is challenging, and appropriate simulation of the tumor microenvironment with mimetic cancer-stroma crosstalk is essential. β4 integrin is known to contribute to triggering a variety of different signaling cues involved in the malignant phenotype of cancer but its role in organ-specific metastasis needs further study. In this work, a multi-compartment microfluidic tumor model was developed to evaluate cancer cell invasion.</div></div><div><h3>Materials and methods</h3><div>To model the primary tumor microenvironment, breast cancer cells (MCF7) and cancer-associated fibroblasts (CAFs) were co-cultured within the tumor compartment of the microfluidic chip while normal lung fibroblasts (NLFs) were seeded in a different compartment, as the secondary tumor site, separated from the tumor compartment via a Matrigel™ layer resembling the extracellular matrix.</div></div><div><h3>Results</h3><div>The cytotoxic effect of β4 integrin blockade on cancer cells gradually increased after 48 and 72 h of co-culture. Invasion of breast cancer cells in both single and coculture models was characterized in response to β4 integrin blockade. The invasion rate and gap closure of MCF7/CAF_NLF was significantly higher than MCF7_NLF (<em>P</em> &lt; 0.0001). β4 integrin inhibition reduced the rate of gap closure and invasion of both (<em>P</em> &lt; 0.0001).</div></div><div><h3>Conclusions</h3><div>Biomimetic microfluidic-based tumor models hold promise for studying cancer metastasis mechanisms. Precise manipulation, simulation, and analysis of the cancer microenvironment are made possible by microfluidics.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102303"},"PeriodicalIF":5.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143182249","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":"Decoding mutational signatures in breast cancer: Insights from a multi-cohort study","authors":"Margaux Betz ,&nbsp;Andréa Witz ,&nbsp;Julie Dardare ,&nbsp;Cassandra Michel ,&nbsp;Vincent Massard ,&nbsp;Romain Boidot ,&nbsp;Pauline Gilson ,&nbsp;Jean-Louis Merlin ,&nbsp;Alexandre Harlé","doi":"10.1016/j.tranon.2025.102315","DOIUrl":"10.1016/j.tranon.2025.102315","url":null,"abstract":"<div><h3>Purpose</h3><div>Diagnosis and treatment decisions of hormonal breast cancers (BC) are now guided by genomic mutations determination, combined into mutational signatures, and provide insight into the patients’ genomic landscape. This work aims to compare genomic data and signatures extracted from tissue samples collected in the CICLADES study to existing cohorts. Ultimately, the goal is to prove the accuracy of smaller cohorts and provide new relevant data.</div></div><div><h3>Materials and methods</h3><div>DNA from patients of the CICLADES cohort was extracted, sequenced, and custom filtering was applied to the resulting files. Genomic data was pulled from 6 BC cohorts available on cBioPortal.com. In total, 2303 samples were analyzed. Mutational signatures were extracted and matched to known signatures of the Catalogue of Somatic Mutations in Cancer (COSMIC). Tumor Mutation Burden (TMB) and hypermutation were estimated and compared between samples.</div></div><div><h3>Results</h3><div><em>PIK3CA</em> and <em>TP53</em> represented the two genes highly mutated across all cohorts. TMB was similar between the CICLADES and CBSM groups, however the MSKCC population showed a significantly higher TMB than both. Nine signatures were extracted, with recurring Single Base Substitutions (SBS) signatures like SBS1, SBS2 and SBS5. The presence of APOBEC-specific signatures was concordant with cohorts presenting APOBEC enrichment. The mean number of mutations was significantly higher in enriched samples for each analyzed cohort.</div></div><div><h3>Conclusion</h3><div>The use of comprehensive genomic profiling provided accurate evaluation of the TMB and extraction of signatures consistent with published literature. The genomic analysis of the tissue samples of the CICLADES cohort brings new and relevant data, comparable to results found in bigger cohorts.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102315"},"PeriodicalIF":5.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143182251","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":"Uncarboxylated osteocalcin induced miR-143-3p targets SP7 and activates PI3K/Akt signaling in TNBC cells to promote invasion and migration","authors":"Qian Du,&nbsp;Jiaojiao Xu,&nbsp;Miao Zhang,&nbsp;Jianhong Yang","doi":"10.1016/j.tranon.2025.102305","DOIUrl":"10.1016/j.tranon.2025.102305","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is an exceptionally aggressive malignancy with poor prognosis. Patients often have elevated mortality and recurrence rates, along with a pronounced risk of distant metastasis. Our earlier research highlighted the role of uncarboxylated osteocalcin (GluOC) in fueling TNBC cell proliferation and metastasis; however the molecular underpinnings of its impact on cancer invasion and migration remain enigmatic. In this study, we identified miR-143-3p as a significantly downregulated miRNA following GluOC treatment in TNBC cells. Notably, increased miR-143-3p has been linked to more favorable clinical outcomes in patients with TNBC. miR-143-3p expression has been shown to target and repress the expression of SP7. Furthermore, our findings indicate that GluOC modulates the miR-143-3p/PI3K/Akt signaling pathway, which in turn fosters the invasive and migratory capabilities of TNBC cells. In a xenograft animal model, we observed that the administration of GluOC led to a marked enhancement in tumor growth. Conversely, the delivery of miR-143-3p agomir was associated with a notable reduction in tumor growth. Notably, concurrent administration of miR-143-3p agomir and GluOC partially abrogated the tumorigenic effects induced by GluOC alone. Furthermore, GluOC downregulated the expression of miR-143-3p. Our study findings indicate that GluOC plays a role in the invasion and migration of TNBC cells by regulating the miR-143-3p/SP7 and miR-143-3p/PI3K/Akt axes. These insights suggest that GluOC and miR-143-3p are integral to the invasive and migratory processes of TNBC cells and may serve as promising targets for therapeutic interventions in TNBC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102305"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143181352","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 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}