Cancer Genomics & Proteomics最新文献

{"title":"A Multiplex Biomarker Assay Improves the Prediction of Survival in Epithelial Ovarian Cancer.","authors":"Arturas Dobilas,&nbsp;Anna Åkesson,&nbsp;Pia Leandersson,&nbsp;Christer Borgfeldt","doi":"10.21873/cgp.20380","DOIUrl":"https://doi.org/10.21873/cgp.20380","url":null,"abstract":"<p><strong>Background/aim: </strong>Epithelial ovarian cancer (EOC) is usually diagnosed in advanced stages and has a high mortality rate. In this study, we used the proximity extension assay from Olink Proteomics to search for new plasma protein biomarkers to predict overall survival (OS) in patients with EOC.</p><p><strong>Materials and methods: </strong>Peripheral blood samples were obtained preoperatively from 116 EOC patients undergoing primary debulking surgery: 28 early EOC cases (FIGO stage I-II) and 88 advanced EOC cases (FIGO stage III-IV). Proteins were measured using the Olink Oncology II and Inflammation panels. In total, 177 unique protein biomarkers were analysed. Cross-validation and LASSO regression were combined to select prediction models for OS.</p><p><strong>Results: </strong>The model including age and the three-biomarker combination of neurotrophin-3 (NT-3)+transmembrane glycoprotein NMB (GPNMB)+mesothelin (MSLN) predicted worse OS with AUC=0.79 (p=0.004). Adding cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to the model further improved performance (AUC=0.83; p=0.003). In a postoperative model including age and stage (III+IV vs. I+II), the three-biomarker panel of chemokine (C-C motif) ligand 28 (CCL28)+T-cell leukaemia/lymphoma protein 1A (TCL1A)+GPNMB improved the prediction of OS (from AUC=0.83 to AUC=0.90; p=0.05). In the postoperative model including age and dichotomized stage (III vs. I+II), the biomarkers CCL28 and GPNMB1 improved the prediction of OS (AUC=0.86; p<0.001). The combination of high levels of both CA125 and HE4 predicted worse survival (p=0.05).</p><p><strong>Conclusion: </strong>In this explorative study evaluating the performance of plasma protein biomarkers in predicting OS, we found that adding biomarkers, especially NT-3, to the panel improved the prediction of OS.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148067/pdf/cgp-20-273.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9404709","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":"Knockdown of G Protein-coupled Estrogen Receptor 1 (GPER1) Enhances Tumor-supportive Properties in Cervical Carcinoma Cells.","authors":"Sophia Ruckriegl,&nbsp;Johanna Loris,&nbsp;Katsiaryna Wert,&nbsp;Gerd Bauerschmitz,&nbsp;Julia Gallwas,&nbsp;Carsten Gründker","doi":"10.21873/cgp.20381","DOIUrl":"https://doi.org/10.21873/cgp.20381","url":null,"abstract":"<p><strong>Background/aim: </strong>A wide variety of answers can be found regarding the question of whether G-protein-coupled estrogen receptor 1 (GPER1) is tumor supportive or tumor suppressive. In cervical carcinoma (CC), the function of GPER1 is poorly understood. In this work, we aimed to clarify what role GPER1 plays in CC, tumor promoting of tumor suppressive.</p><p><strong>Materials and methods: </strong>Transient GPER1 silencing was conducted using RNAi and approved by RT-qPCR. Clonogenic potential was tested by colony and sphere formation. Expression of SERPINE1/PAI-1 was quantified by RT-qPCR and Western blot. Morphological changes were analyzed using Phalloidin staining. Localization of GPER1 in tumor spheres was examined by immunofluorescence.</p><p><strong>Results: </strong>After GPER1 knockdown, more colonies formed in HeLa and SiHa, and larger colonies formed in C33-A and SiHa CC cells. Size of HeLa and SiHa tumor spheres was also increased. In addition, number of HeLa tumor spheres was elevated, and larger secondary colonies were present. C33-A only formed tumor sphere-like clusters showing no differences in number and size. Phalloidin staining revealed greater cellular length-to-width ratio and increased average filopodia length. Expression of SERPINE1/PAI-1 was increased in HeLa and decreased in C33-A. In SiHa cells, SERPINE1 was slightly decreased, whereas the protein PAI-1 was increased. Strong expression of GPER1 was detectable in peripheral areas and in sprouts of tumor spheres.</p><p><strong>Conclusion: </strong>GPER1 appears to be tumor suppressive in CC, as GPER1 knockdown provoked increased stem cell properties and increased migration/invasion. EMT also appears to be enhanced. Of interest is the increase in SERPINE1/PAI-1 expression after GPER1 knockdown.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148066/pdf/cgp-20-281.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9409954","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":"Biospecimen Digital Twins: Moving from a \"High Quality\" to a \"Fit-for-Purpose\" Concept in the Era of Omics Sciences.","authors":"Umberto Nanni,&nbsp;Patrizia Ferroni,&nbsp;Silvia Riondino,&nbsp;Antonella Spila,&nbsp;Maria Giovanna Valente,&nbsp;Girolamo Del Monte,&nbsp;Mario Roselli,&nbsp;Fiorella Guadagni","doi":"10.21873/cgp.20376","DOIUrl":"https://doi.org/10.21873/cgp.20376","url":null,"abstract":"<p><p>The growing demand for personalized medicine we are currently witnessing has given rise to more in-depth research in the field of biomarker discovery and, thus, in biological banks that hold the ability to process, collect, store, and distribute \"high-quality\" biological specimens. However, the notion of \"specimen quality\" is subject to change with technological advancements. In this perspective, we propose that the notion of sample quality should shift from a broad definition of \"high-quality\" to a \"fit-for-purpose\" concept more suitable for precision medicine studies. Digital twins are a digital replica of real entities. These are largely adopted in any digitalized domain and are currently finding applications in biomedicine. The adoption of digital twins for biosamples, proposed in this paper, can provide prompt information about the whole lifecycle of the physical twin (i.e., the biosample) and substantially extend the possible matching criteria between the available samples and the researchers' and physicians' requests. This fine-tuning matching could greatly contribute to improving the \"fit-for-purpose\" quality, not only for studies based on current needs, but also to improve the identification of the best available samples in future situations, determined by the evolution of technologies and biosciences. Assuming and exploiting a data-science view in our biobank perspective, the more (accurate) data there are available, the more information can be extrapolated from them, the more opportunities there are for matching future, currently unknown, needs. This should be a mandatory principle that the 'time machines' called biobanks should follow.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148068/pdf/cgp-20-211.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9409957","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":"A Bioinformatics Assessment Indicating Better Outcomes With Breast Cancer Resident, Immunoglobulin CDR3-MMP2 Binding.","authors":"Suhaas R Mandala,&nbsp;Alexis J Thomson,&nbsp;Etienne C Gozlan,&nbsp;Dhruv N Patel,&nbsp;Andrea Chobrutskiy,&nbsp;Boris I Chobrutskiy,&nbsp;George Blanck","doi":"10.21873/cgp.20378","DOIUrl":"https://doi.org/10.21873/cgp.20378","url":null,"abstract":"<p><strong>Background/aim: </strong>The recombination of V, D, and J immunoglobulin (IG) gene segments leads to many variations in the amino acids (AAs) encoded at that site, the complementarity determining region-3 (CDR3). Thus, cancer patients may have varying degrees of CDR3 AA binding specificity for cancer proteases, for example, matrix metalloproteinase 2 (MMP2). MMP2 in breast cancer has been found to contribute to metastasis and is used as a marker for tumor staging. Thus, this report evaluated the tumor resident, patient specific IG CDR3 binding affinities to cancer proteases to test the hypothesis that greater binding affinities would be associated with a better outcome.</p><p><strong>Materials and methods: </strong>Using two independent bioinformatics tools, we evaluated the IG CDR3-MMP2 binding affinities throughout the cancer genome atlas breast cancer (TCGA-BRCA) dataset.</p><p><strong>Results: </strong>Results indicated that the better the CDR3-MMP2 binding, the better the survival probability. An analogous evaluation for four other proteases, including calpain-1 and thermolysin, displayed no such associations with survival probabilities.</p><p><strong>Conclusion: </strong>This study is consistent with the possibility that patient IG-cancer protease interactions could impact outcomes and raises the question of whether therapeutic antibody targeting of MMP2 would reduce breast cancer mediated tissue destruction and breast cancer mortality rates.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148069/pdf/cgp-20-239.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9409956","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":"Loss of F-Box and Leucine Rich Repeat Protein 5 (FBXL5) Expression Is Associated With Poor Survival in Patients With Hepatocellular Carcinoma After Curative Resection: A Two-institute Study.","authors":"Yoon Ah Cho,&nbsp;Sung-Eun Kim,&nbsp;Cheol Keun Park,&nbsp;Hyun Hee Koh,&nbsp;Cheol-Keun Park,&nbsp;Sang Yun Ha","doi":"10.21873/cgp.20382","DOIUrl":"https://doi.org/10.21873/cgp.20382","url":null,"abstract":"<p><strong>Background/aim: </strong>Alteration of F-box and leucine-rich repeat protein 5 (FBXL5), an iron-sensing ubiquitin ligase, might be related with carcinogenesis of hepatocellular carcinoma (HCC), by disturbing cellular iron homeostasis. However, the clinical implications of FBXL5 expression using patient samples need to be elucidated.</p><p><strong>Patients and methods: </strong>We collected HCC tissue samples from two institutes: Samsung Medical Center (n=259) and Hallym University Sacred Heart Hospital (n=115) and evaluated FBXL5 expression using immunohistochemistry. Using cut-off values determined by X-tile software, association between FBXL5 expression and several clinicopathological parameters was investigated. For external validation, the Cancer Genome Atlas (TCGA) cohort was used.</p><p><strong>Results: </strong>The best cutoff value for FBXL5 IHC expression associated with recurrence-free survival (RFS) was 5%. Low FBXL5 expression was found in 18.7% of the total 374 HCCs and was associated with non-viral etiology (p=0.019). Low FBXL5 expression was related with inferior disease-specific survival (DSS, p=0.002) and RFS (p=0.001) and also was an independent prognostic factor for DSS and RFS. In addition, cases with low FBLX5 mRNA levels showed inferior DSS and RFS (p<0.001 and p=0.002, respectively) compared to high FBLX5 mRNA levels in the TCGA cohort.</p><p><strong>Conclusion: </strong>Down-regulation of FBXL5 expression in HCCs might be associated with poor prognosis. FBXL5 might be a prognostic biomarker of HCCs and a potential therapeutic target in conjunction with iron homeostasis.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148071/pdf/cgp-20-298.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9459806","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":"Up-regulated Circular RNAs in Colorectal Cancer: New Entities for Therapy and Tools for Identification of Therapeutic Targets.","authors":"Ulrich H Weidle, Adam Nopora","doi":"10.21873/cgp.20369","DOIUrl":"10.21873/cgp.20369","url":null,"abstract":"<p><p>Patients with disseminated colorectal cancer have a dismal prognosis with a 5-year survival rate of only 13%. In order to identify new treatment modalities and new targets, we searched the literature for up-regulated circular RNAs in colorectal cancer which induce tumor growth in corresponding preclinical in vivo models. We identified nine circular RNAs that mediate resistance against chemotherapeutic agents, seven that up-regulate transmembrane receptors, five that induce secreted factors, nine that activate signaling components, five which up-regulate enzymes, six which activate actin-related proteins, six which induce transcription factors and two which up-regulate the MUSASHI family of RNA binding proteins. All of the circular RNAs discussed in this paper induce the corresponding targets by sponging microRNAs (miRs) and can be inhibited by RNAi or shRNA in vitro and in xenograft models. We have focused on circular RNAs with demonstrated activity in preclinical in vivo models because the latter is an important milestone in drug development. All circular RNAs with in vitro activity only data are not referenced in this review. The translational impact of inhibition of these circular RNAs and of the identified targets for treatment of colorectal cancer (CRC) are discussed.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989668/pdf/cgp-20-132.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9074919","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":"Recurrent 8q11-13 Aberrations Leading to <i>PLAG1</i> Rearrangements, Including Novel Chimeras <i>HNRNPA2B1::PLAG1</i> and <i>SDCBP::PLAG1</i>, in Lipomatous Tumors.","authors":"Ioannis Panagopoulos, Kristin Andersen, Ludmila Gorunova, Marius Lund-Iversen, Ingvild Lobmaier, Francesca Micci, Sverre Heim","doi":"10.21873/cgp.20372","DOIUrl":"10.21873/cgp.20372","url":null,"abstract":"<p><strong>Background/aim: </strong>Structural abnormalities of chromosome bands 8q11-13, resulting in rearrangement of the pleomorphic adenoma gene 1 (PLAG1), are known to characterize lipoblastoma, a benign fat cell tumor, found mainly in children. Here, we describe 8q11-13 rearrangements and their molecular consequences on PLAG1 in 7 lipomatous tumors in adults.</p><p><strong>Materials and methods: </strong>The patients were 5 males and 2 females between 23 and 62 years old. The tumors, namely five lipomas, one fibrolipoma and one spindle cell lipoma, were examined using G-banding with karyotyping, fluorescence in situ hybridization (FISH; three tumors), RNA sequencing, reverse transcription (RT) PCR, and Sanger sequencing analyses (two tumors).</p><p><strong>Results: </strong>All 7 tumors had karyotypic aberrations which included rearrangements of chromosome bands 8q11-13 (the criterion for selection into this study). FISH analyses with a PLAG1 break apart probe showed abnormal hybridization signals in both interphase nuclei and on metaphase spreads indicating PLAG1 rearrangement. RNA sequencing detected fusion between exon 1 of heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) and exon 2 or 3 of PLAG1 in a lipoma and fusion between exon 2 of syndecan binding protein (SDCBP) and exon 2 or 3 of PLAG1 in a spindle cell lipoma. The HNRNPA2B1::PLAG1 and SDCBP::PLAG1 fusion transcripts were confirmed using RT-PCR/Sanger sequencing analyses.</p><p><strong>Conclusion: </strong>As 8q11-13 aberrations/PLAG1-rearrangements/PLAG1-chimeras may evidently be a defining pathogenetic feature of lipogenic neoplasms of several histological types and not just lipoblastomas, we suggest that the term \"8q11-13/PLAG1-rearranged lipomatous tumors\" be generally adopted for this tumor subset.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989671/pdf/cgp-20-171.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10869924","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":"Triple-negative Breast Cancer: Identification of circRNAs With Efficacy in Preclinical <i>In Vivo</i> Models.","authors":"Ulrich H Weidle,&nbsp;Fabian Birzele","doi":"10.21873/cgp.20368","DOIUrl":"https://doi.org/10.21873/cgp.20368","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with insufficient options for therapy. In order to identify new targets and treatment modalities we searched the literature for circular RNAs (circRNAs) which mediate efficacy in TNBC-related in vivo preclinical models. In addition to 5 down-regulated circRNAs which modulate tumor-suppressive pathways, we identified 15 up-regulated circRNAs. Down- and up-regulated refers to expression in corresponding non-transformed cells and tissues. The up-regulated circRNAs comprise five transmembrane receptors and secreted proteins as targets, five transcription factors and transcription-associated targets, four cell-cycle related circRNAs and one involved in paclitaxel resistance. In this review article we discuss drug-discovery related aspects and modalities of therapeutic intervention. Down-regulated circRNAs can be reconstituted by re-expression of corresponding circRNAs in tumor cells or up-regulation of corresponding targets. Up-regulated circRNAs can be inhibited by small-interfering RNA (siRNA) or short hairpin RNA (shRNA)-based approaches or inhibition of the corresponding targets with small molecules or antibody-related moieties.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989670/pdf/cgp-20-117.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9074917","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":"Oncogenes and Methionine Addiction of Cancer: Role of <i>c-MYC</i>.","authors":"Yusuke Aoki,&nbsp;Qinghong Han,&nbsp;Yutaro Kubota,&nbsp;Noriyuki Masaki,&nbsp;Koya Obara,&nbsp;Yasunori Tome,&nbsp;Michael Bouvet,&nbsp;Kotaro Nishida,&nbsp;Robert M Hoffman","doi":"10.21873/cgp.20371","DOIUrl":"https://doi.org/10.21873/cgp.20371","url":null,"abstract":"<p><strong>Background/aim: </strong>Methionine addiction is a general and fundamental hallmark of cancer cells, termed the Hoffman effect. Previously Vanhamme and Szpirer showed that methionine addiction could be induced by transfection of the activated HRAS1 gene to a normal cell line. In the present study, we investigated the role of the c-MYC oncogene in methionine addiction of cancer, by comparison of c-Myc expression and malignancy of methionine-addicted osteosarcoma cells and rare methionine-independent revertants, derived from the methionine-addicted cells.</p><p><strong>Materials and methods: </strong>Methionine-independent revertant 143B osteosarcoma cells (143B-R) were derived from methionine-addicted parental 143B osteosarcoma cells (143B-P), by continuous culture in medium depleted of methionine by recombinant methioninase. To compare in vitro malignancy of methionine-addicted parental cells and methionine-independent revertant cells, the following experiments were performed: for 143B-P and 143B-R cells, cell proliferation capacity was measured with a cell-counting assay, and colony-formation capacity was determined on plastic and in soft agar, all in methionine-containing Dulbecco's Modified Eagle's Medium (DMEM). Tumor growth was measured in orthotopic xenograft nude-mouse models, to compare in vivo malignancy of 143B-P and 143B-R cells. c-MYC expression was examined with western immunoblotting and compared in 143B-P and 143B-R cells.</p><p><strong>Results: </strong>143B-R cells had reduced cell proliferation capacity, compared to 143B-P cells, in methionine-containing medium (p=0.003). 143B-R cells had reduced colony formation capacity on plastic (p=0.003) and in soft agar, compared to 143B-P cells in methionine-containing medium. 143B-R cells had reduced tumor growth in orthotopic xenograft nude-mouse models, compared to 143B-P cells, (p=0.002). These results demonstrate that 143B-R methionine-independent revertant cells lost malignancy. Expression of c-MYC was reduced in 143B-R methionine-independent revertant osteosarcoma cells, compared to 143B-P cells, (p=0.0007).</p><p><strong>Conclusion: </strong>The present study demonstrated that c-MYC expression is linked to malignancy and methionine addiction of cancer cells. The present study on c-MYC, and the previous study on HRAS1, suggest that oncogenes may play a role in methionine addiction, which is a hallmark of all cancers, as well as in malignancy.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989672/pdf/cgp-20-165.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9074918","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":"Receptor for Hyaluronic Acid-mediated Motility (RHAMM) Is Associated With Prostate Cancer Migration and Poor Prognosis.","authors":"Akinori Minato,&nbsp;Yuzan Kudo,&nbsp;Hirotsugu Noguchi,&nbsp;Shiro Kohi,&nbsp;Yoshitaka Hasegawa,&nbsp;Norihiro Sato,&nbsp;Keiji Hirata,&nbsp;Naohiro Fujimoto","doi":"10.21873/cgp.20375","DOIUrl":"https://doi.org/10.21873/cgp.20375","url":null,"abstract":"<p><strong>Background/aim: </strong>Hyaluronic acid (HA) is a large glycosaminoglycan composed of an extracellular matrix. The HA-rich microenvironment and receptors of HA have been suggested to play roles in cancer progression. The biological and clinical significance of receptor for HA-mediated motility (RHAMM), known as CD168 in prostate cancer (PC) remains unknown. This study aimed to investigate the expression of RHAMM, as well as its functional and clinical relevance in PC.</p><p><strong>Materials and methods: </strong>HA concentration and RHAMM mRNA expression were examined in 3 PC cell lines (LNCaP, PC3 and DU145). We investigated the effect of HA and RHAMM on the migratory ability of PC cells using a transwell migration assay. Immunohistochemistry was also used to evaluate the RHAMM expression pattern in pre-treatment tissue samples from 99 patients with metastatic hormone-sensitive PC (HSPC) who received androgen deprivation therapy (ADT).</p><p><strong>Results: </strong>HA was secreted in all cultured PC cell lines. Among the total HA, low-molecular-weight HA (LMW-HA) (<100 kDa) was detected all examined cell lines. The number of migration cells was significantly increased by adding LMW-HA. RHAMM mRNA expression was increased in DU145 cells. Knockdown of RHAMM using small-interfering RNA resulted in decreased cell migration. Immunohistochemical analysis revealed strong RHAMM expression in 31 (31.3%) patients with metastatic HSPC. A strong RHAMM expression was significantly associated with short ADT duration and poor survival in univariate and multivariate analyses.</p><p><strong>Conclusion: </strong>The size of HA is important in terms of PC progression. LMW-HA and RHAMM enhanced PC cell migration. RHAMM could be used as a novel prognostic marker in patients with metastatic HSPC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989669/pdf/cgp-20-203.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10869923","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}