Cancer Genomics & Proteomics最新文献

{"title":"CEACAM6 Promotes Lung Metastasis <i>via</i> Enhancing Proliferation, Migration and Suppressing Apoptosis of Prostate Cancer Cells.","authors":"Alireza Saraji, Katharina Wulf, Janine Stegmann-Frehse, Duan Kang, Anne Offermann, Gevorg Shaghoyan, Danny Jonigk, Mark Philipp Kühnel, Sven Perner, Jutta Kirfel, Verena Sailer","doi":"10.21873/cgp.20459","DOIUrl":"10.21873/cgp.20459","url":null,"abstract":"<p><strong>Background/aim: </strong>Metastatic prostate cancer (mPCa) results in high morbidity and mortality. Visceral metastases in particular are associated with a shortened survival. Our aim was to unravel the molecular mechanisms that underly pulmonary spread in mPCa.</p><p><strong>Materials and methods: </strong>We performed a comprehensive transcriptomic analysis of PCa lung metastases, followed by functional validation of candidate genes. Digital gene expression analysis utilizing the NanoString technology was performed on mRNA extracted from formalin-fixed, paraffin-embedded (FFPE) tissue from PCa lung metastases. The gene expression data from primary PCa and PCa lung metastases were compared, and several publicly available bioinformatic analysis tools were used to annotate and validate the data.</p><p><strong>Results: </strong>In PCa lung metastases, 234 genes were considerably up-regulated, and 78 genes were significantly down-regulated when compared to primary PCa. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) was identified as suitable candidate gene for further functional validation. CEACAM6 as a cell adhesion molecule has been implicated in promoting metastatic disease in several solid tumors, such as colorectal or gastric cancer. We showed that siRNA knockdown of CEACAM6 in PC-3 and LNCaP cells resulted in decreased cell viability and migration as well as enhanced apoptosis. Comprehensive transcriptomic analyses identified several genes of interest that might promote metastatic spread to the lung.</p><p><strong>Conclusion: </strong>Functional validation revealed that CEACAM6 might play an important role in fostering metastatic spread to the lung of PCa patients via enhancing proliferation, migration and suppressing apoptosis in PC-3 and LNCaP cells. CEACAM6 might pose an attractive therapeutic target to prevent metastatic disease.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 4","pages":"405-413"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466365","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":"CircRNAs in Pancreatic Cancer: New Tools for Target Identification and Therapeutic Intervention.","authors":"Ulrich H Weidle, Adam Nopora","doi":"10.21873/cgp.20451","DOIUrl":"10.21873/cgp.20451","url":null,"abstract":"<p><p>We have reviewed the literature for circular RNAs (circRNAs) with efficacy in preclinical pancreatic-cancer related in vivo models. The identified circRNAs target chemoresistance mechanisms (n=5), secreted proteins and transmembrane receptors (n=15), transcription factors (n=9), components of the signaling- (n=11), ubiquitination- (n=2), autophagy-system (n=2), and others (n=9). In addition to identifying targets for therapeutic intervention, circRNAs are potential new entities for treatment of pancreatic cancer. Up-regulated circRNAs can be inhibited by antisense oligonucleotides (ASO), small interfering RNAs (siRNAs), short hairpin RNAs (shRNAs) or clustered regularly interspaced short-palindromic repeats-CRISPR associated protein (CRISPR-CAS)-based intervention. The function of down-regulated circRNAs can be reconstituted by replacement therapy using plasmids or virus-based vector systems. Target validation experiments and the development of improved delivery systems for corresponding agents were examined.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 4","pages":"327-349"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466366","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":"Photoimmunotherapy of HER2-expressing Breast Cancer Cells.","authors":"Lukas Klemenz, Isis Wolf, Jonas Storz, Susanne Schultze-Seemann, Christian Gratzke, Susan Lauw, Reinhard Brückner, Philipp Wolf","doi":"10.21873/cgp.20453","DOIUrl":"10.21873/cgp.20453","url":null,"abstract":"<p><strong>Background/aim: </strong>Breast cancer (BC) is the most common malignant disease worldwide. Localized stages of BC can be successfully treated by surgery. However, local recurrence occurs in about 4-10% of patients, requiring systemic treatments that impair the patients' quality of life and shortens life expectancy. Therefore, new therapeutic options are needed, which can be used intraoperatively and contribute to the complete removal of residual tumor cells in the surgical area. In the present study, we describe a cysteine-modified variant of the anti-HER2 antibody trastuzumab, that was coupled to the silicon phthalocyanine photosensitizer dye WB692-CB1 for the photoimmunotherapy (PIT) of BC.</p><p><strong>Materials and methods: </strong>The cysteine modified trastuzumab variant was cloned and expressed in Expi293F cells. After purification via immobilized affinity chromatography, the antibody was coupled to the dye. Cell binding of the antibody and the antibody dye conjugate was measured by flow cytometry. After incubation of BC cells with the conjugate and activation of the dye by irradiation with red light, cell viability was determined.</p><p><strong>Results: </strong>The antibody and the conjugate showed specific binding to HER2-expressing BC cells. Treatment of the HER2^high BC cell line SK-BR-3 with the conjugate followed by irradiation with a red light dose of 32 J/cm² led to complete cell killing within 24 h.</p><p><strong>Conclusion: </strong>Our novel antibody dye conjugate represents a promising candidate for intraoperative treatment of localized BC, aiming to eliminate residual tumor cells in the surgical area and potentially reduce local recurrence, thereby improving recovery prospects for BC patients.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 4","pages":"361-367"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466342","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":"Melatonin Inhibits Chemical Carcinogen-mediated Malignant Transformation of Urothelial Cells: <i>In Vitro</i> Evidence.","authors":"Yujiro Nagata, Nguyen Thu Quynh, Hisami Aono, Kenichi Harada, Hiroshi Miyamoto, Naohiro Fujimoto","doi":"10.21873/cgp.20456","DOIUrl":"10.21873/cgp.20456","url":null,"abstract":"<p><strong>Background/aim: </strong>The efficacy of melatonin and its biological significance in human bladder cancer remain poorly understood. This study aimed to investigate the functional role of melatonin in urothelial carcinogenesis.</p><p><strong>Materials and methods: </strong>In human normal urothelial SVHUC cells with exposure to the chemical carcinogen 3-methylcholanthrene, we assessed the effects of melatonin on the neoplastic/malignant transformation.</p><p><strong>Results: </strong>In the in vitro system with carcinogen challenge, melatonin significantly prevented the neoplastic transformation of SV-HUC-1 cells. In addition, melatonin treatment resulted in increased expression of SIRT1, Rb1, and E-cadherin, and decreased expression of N-cadherin and FGFR3 in SV-HUC-1 cells. Furthermore, publicly available datasets from GSE3167 revealed that the expression of melatonin receptor 1 and melatonin receptor 2 was significantly down-regulated in bladder urothelial carcinoma tissues, compared with adjacent normal urothelial tissues.</p><p><strong>Conclusion: </strong>These findings indicate that melatonin serves as a suppressor for urothelial tumorigenesis. To the best of our knowledge, this is the first preclinical study demonstrating the impact of melatonin on the development of urothelial cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 4","pages":"388-394"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466341","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":"Restoration of ARID1A Protein in ARID1A-deficient Clear Cell Carcinoma of the Ovary Attenuates Reactivity to Cytotoxic T Lymphocytes.","authors":"Risa Tsunematsu, Aiko Murai, Yuka Mizue, Terufumi Kubo, Tasuku Mariya, Rena Morita, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Tsuyoshi Saito, Toshihiko Torigoe","doi":"10.21873/cgp.20460","DOIUrl":"10.21873/cgp.20460","url":null,"abstract":"<p><strong>Background/aim: </strong>Clear cell carcinoma is a prevalent histological type of ovarian cancer in East Asia, particularly in Japan, known for its resistance to chemotherapeutic agents and poor prognosis. ARID1A gene mutations, commonly found in ovarian clear cell carcinoma (OCCC), contribute to its pathogenesis. Recent data revealed that the ARID1A mutation is related to better outcomes of cancer immunotherapy. Thus, this study aimed to investigate the immunotherapy treatment susceptibility of OCCC bearing ARID1A mutations.</p><p><strong>Materials and methods: </strong>Expression of ARID1A was analyzed using western blotting in ovarian cancer cell lines. OCCC cell lines JHOC-9 and RMG-V were engineered to overexpress NY-ESO-1, HLA-A*02:01, and ARID1A. Sensitivity to chemotherapy and T cell receptor-transduced T (TCR-T) cells specific for NY-ESO-1 was assessed in ARID1A-restored cells compared to ARID1A-deficient wild-type cells.</p><p><strong>Results: </strong>JHOC-9 cells and RMG-V cells showed no expression of ARID1A protein. Overexpression of ARID1A in JHOC-9 and RMG-V cells did not impact sensitivity to gemcitabine. While ARID1A overexpression decreased sensitivity to cisplatin in RMG-V cells, it had no such effect in JHOC-9 cells. ARID1A overexpression reduced the reactivity of NY-ESO-1-specific TCR-T cells, as observed by the IFNγ ESLIPOT assay.</p><p><strong>Conclusion: </strong>Cancer immunotherapy is an effective approach to target ARID1A-deficient clear cell carcinoma of the ovary.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 4","pages":"414-420"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466343","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":"Transcriptomic Analysis of Metastatic Uveal Melanoma and Differences in Male and Female Patients.","authors":"Sishir Doddi, Abdul-Rizaq Hamoud, Hunter M Eby, Xiaolu Zhang, Ali Sajid Imami, Elizabeth Shedroff, Isaac Schiefer, Jose Moreno-Lopez, David Gamm, Jaroslaw Meller, Robert E McCullumsmith","doi":"10.21873/cgp.20452","DOIUrl":"10.21873/cgp.20452","url":null,"abstract":"<p><strong>Background/aim: </strong>Uveal melanoma is an ocular malignancy whose prognosis severely worsens following metastasis. In order to improve the understanding of molecular physiology of metastatic uveal melanoma, we identified genes and pathways implicated in metastatic vs non-metastatic uveal melanoma.</p><p><strong>Patients and methods: </strong>A previously published dataset from Gene Expression Omnibus (GEO) was used to identify differentially expressed genes between metastatic and non-metastatic samples as well as to conduct pathway and perturbagen analyses using Gene Set Enrichment Analysis (GSEA), EnrichR, and iLINCS.</p><p><strong>Results: </strong>In male metastatic uveal melanoma samples, the gene LOC401052 is significantly down-regulated and FHDC1 is significantly up-regulated compared to non-metastatic male samples. In female samples, no significant differently expressed genes were found. Additionally, we identified many significant up-regulated immune response pathways in male metastatic uveal melanoma, including \"T cell activation in immune response\". In contrast, many top up-regulated female pathways involve iron metabolism, including \"heme biosynthetic process\". iLINCS perturbagen analysis identified that both male and female samples have similar discordant activity with growth factor receptors, but only female samples have discordant activity with progesterone receptor agonists.</p><p><strong>Conclusion: </strong>Our results from analyzing genes, pathways, and perturbagens demonstrate differences in metastatic processes between sexes.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 4","pages":"350-360"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466344","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":"Impact of Prospero Homeobox-1 (PROX-1) οn the Oncogenic Phenotypes of Hepatocellular Carcinoma Cells.","authors":"Ji-Yun Hong, Sun-Young Park, Young-Lan Park, Ga-Ram You, Jae Hyun Yoon, Young-Eun Joo, Sung Kyu Choi, Sung-Bum Cho","doi":"10.21873/cgp.20448","DOIUrl":"https://doi.org/10.21873/cgp.20448","url":null,"abstract":"Transcriptional factor prospero homeobox-1 (PROX-1) is crucial for the embryonic development of various organs and cell fate specification. It exhibits either an oncogenic or tumor suppressive activity depending on cancer types. However, the relationship between PROX-1 and hepatocellular carcinoma (HCC) remains obscure. This study was conducted to investigate the effect of PROX-1 on the invasive and oncogenic phenotypes of human HCC cells.","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"17 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140805896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline MYOF1::WNK4 and VPS25::MYOF1 Chimeras Generated by the Constitutional Translocation t(17;19)(q21;p13) in Two Siblings With Myelodysplastic Syndrome.","authors":"Ioannis Panagopoulos, Kristin Andersen, Vidar Stavseth, Synne Torkildsen, Sverre Heim, Maren Randi Tandsæther","doi":"10.21873/cgp.20446","DOIUrl":"https://doi.org/10.21873/cgp.20446","url":null,"abstract":"Constitutional chromosomal aberrations are rare in hematologic malignancies and their pathogenetic role is mostly poorly understood. We present a comprehensive molecular characterization of a novel constitutional chromosomal translocation found in two siblings - sisters - diagnosed with myelodysplastic syndrome (MDS).","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"41 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140806172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Frequencies of Dynamic DNA Sequences and Mammalian Lifespan.","authors":"Marianna Martella, Nadia Carlesso, Zoë A E Waller, Guido Marcucci, Flavia Pichiorri, Steven S Smith","doi":"10.21873/cgp.20443","DOIUrl":"https://doi.org/10.21873/cgp.20443","url":null,"abstract":"Dynamic DNA sequences (i.e. sequences capable of forming hairpins, G-quadruplexes, i-motifs, and triple helices) can cause replication stress and associated mutations. One example of such a sequence occurs in the RACK7 gene in human DNA. Since this sequence forms i-motif structures at neutral pH that cause replication stress and result in spontaneous deletions in prostate cancer cells, our initial aim was to determine its potential utility as a biomarker of prostate cancer.","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"63 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140805894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fusion of Platelet Derived Growth Factor Receptor Alpha (PDGFRA) With Ubiquitin Specific Peptidase 8 (USP8) in a Calcified Chondroid Mesenchymal Neoplasm Harboring t(4;15)(q12;q21) as a Sole Aberration.","authors":"Ioannis Panagopoulos, Kristin Andersen, Ludmila Gorunova, Ingvild Lobmaier","doi":"10.21873/cgp.20444","DOIUrl":"https://doi.org/10.21873/cgp.20444","url":null,"abstract":"The term \"calcified chondroid mesenchymal neoplasm\" was introduced in 2021 to describe a group of tumors characterized by various morphological features, including the formation of cartilage or chondroid matrix. These tumors frequently carry chimeric genes where the 5'-end partner gene is fibronectin 1 and the 3'-end partner gene codes for receptor tyrosine kinase. Our study explores fusion of the genes platelet-derived growth factor receptor alpha (PDGFRA) and ubiquitin-specific peptidase 8 (USP8) in calcified chondroid mesenchymal neoplasm.","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"28 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140805935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}