Cancer Biomarkers最新文献

{"title":"Integrative analysis of histone acetyltransferase KAT2A in human cancer.","authors":"Hua Li, Chun Li, Lu-Zong Yang, Ji Liu","doi":"10.3233/CBM-220464","DOIUrl":"10.3233/CBM-220464","url":null,"abstract":"<p><p>The high incidence of mutations and the crucial roles of KAT2A in cancer development have received increased attention. Nevertheless, a systematic comparison of the heterogeneity and dynamics across different cancer types has not been conducted. Hence, a deep analysis using public databases was performed to clarify the contributions of KAT2A and its correlation with tumorigenesis. The raw data regarding KAT2A expression in cancer patients and healthy controls were obtained from The Cancer Genome Atlas (TCGA). Sexually dimorphic manner, genomic alterations, and expression pattern of KAT2A, as well as the association of the KAT2A with survival, were retrieved from UALCAN, cBioportal, and TISIDB databases. Additionally, the Protein-Protein Interaction (PPI) analysis was conducted using the STRING database. The human protein atlas was used to obtain the staining results of protein levels in cancer and normal samples. The correlation between KAT2A and its potential target drugs was determined using TISIDB and HISTome2. Compared to the normal tissues, CHOL and TGCT tumors presented significantly high KAT2A expression, which was positively correlated with BLCA, BRCA, CESC, CHOL, COAD, ESCA, HNSC, KICH, KIRP, LIHC, LUAD, LUSC, READ, STAD, and THCA. However, no significant difference was detected between normal and tumor tissues for the sex difference pattern of KAT2A expression. The PPI analysis indicated that TADA3, CCDC101, TRRAP, SUPT3H, MYC, TADA2A, and USP22 levels were positively correlated with KAT2A expression, while TADA2B and ATXN7 were negatively correlated. A positive link of KAT2A with cancer isotypes and significant connections of the KAT2A expression to poor overall and disease-free survival were also observed. Further validation was conducted using immunohistochemistry (IHC) staining, qPCR, and Western blot. Some potential HAT inhibitory drugs of KAT2A were also determined, but more work and clinical trials are required before their application.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441735","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":"Secreted frizzled related-protein 2 is prognostic for human pancreatic cancer patient survival and is associated with fibrosis.","authors":"Julie B Siegel, Patrick Nasarre, Lillian Hsu, Rupak Mukherjee, Meghan Gormley, Bailey Richardson, Imran Khan, Jordan E Morningstar, Eleanor Hilliard, John P O'Bryan, Kristi L Helke, Laura Spruill, Nathan G Dolloff, Nancy Klauber-DeMore","doi":"10.3233/CBM-220044","DOIUrl":"10.3233/CBM-220044","url":null,"abstract":"<p><p>Pancreatic adenocarcinoma (PDAC) is one of the deadliest cancers, with five-year survival rates of 9%. We hypothesized that secreted frizzled-related protein 2 (SFRP2) may influence stromal growth in pancreatic cancer, since it increases fibrosis and collagen production in non-neoplastic pathologies. We assessed SFRP2 value as a biomarker and assessed its function in PDAC. SFRP2 gene expression in patients with PDAC was analyzed using TCGA data. Disease free survival (DFS) was analyzed using Kaplan Meier test. The effect of KRAS inhibition on SFRP2 expression in PDAC cells was assessed. The associations of stromal content with SFPR2 mRNA and protein with fibrosis were analyzed. The role of SFRP2 in mesenchymal transformation was assessed by western blot in fibroblasts. Of all cancers in TCGA, SFRP2 levels were highest in PDAC, and higher in PDAC than normal tissues (n= 234, p= 0.0003). High SFRP2 levels correlated with decreased DFS (p= 0.0097). KRAS inhibition reduced SFRP2 levels. Spearman correlation was 0.81 between stromal RNA and SFRP2 in human PDAC, and 0.75 between fibrosis and SFRP2 levels in PDAC tumors. SFRP2-treated fibroblasts displayed mesenchymal characteristics. SFRP2 is prognostic for PDAC survival, regulated by KRAS, and associated with PDAC fibrosis.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10977449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720828","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":"The clinical value of a nomogram constructed from CEA, CA199, PT, FIB, tumor differentiation and TNM stage in colorectal cancer.","authors":"Kang Wang, Lulu Ma, Liying Chen, Yatong Jiang, Ningquan Liu, Jianchun Cai, Yiyao Zhang","doi":"10.3233/CBM-230116","DOIUrl":"10.3233/CBM-230116","url":null,"abstract":"<p><strong>Background: </strong>The accurate Tumor-Node-Metastasis (TNM) staging of colorectal cancer (CRC) is of great guiding significance for the judgment of tumor progression and prognosis, and the formulation of treatment strategies.</p><p><strong>Objective: </strong>The aim of this study was to construct a recurrence risk scoring (RRS) system and prognostic prediction model to improve the accuracy of staging, prognosis prediction, and clinical decision making in resectable CRC.</p><p><strong>Methods: </strong>CRC patients who underwent radical resection were retrospectively enrolled into study. Multivariable Cox regression model was applied to screen for independent prognostic factors. The RRS system is composed of independent prognostic factors which was awarded 1point each. A prognostic model composed of RRS and TNM staging system (RRS-TNM model) was applied to predict postoperative recurrence.</p><p><strong>Results: </strong>TNM stage, tumor differentiation, preoperative elevated Carcinoembryonic Antigen, Carbohydrate Antigen 199, Prothrombin Time and Fibrinogen were the independent prognostic biomarkers. 173 of 540 patients had recurrence. The 5-year cumulative recurrence rate (5-y CRR) and disease-free survival (DFS) of postoperative p-TNM stage I, II, and III were 12.7% and 104.8 months, 26.5% and 89.3 months, and 55.5% and 57.3 months, respectively. The 5-y CRR and DFS of preoperative Low-risk (RRS 0-1score), Middle-risk (RRS 2-3scores), and High-risk (RRS 4-5scores) groups were 13.9% and 101.1 months, 40.9% and 75.5 months, and 70.2% and 41.1 months. The AUC (area under ROC curve) of RRS system was not inferior to that of TNM staging system (0.713 vs. 0.666; P= 0.093). The AUC (0.770) and C-index value (0.721) of RRS-TNM model were significantly better than both RRS and TNM staging system (P< 0.001).</p><p><strong>Conclusions: </strong>The RRS system accurately identifies CRC patients with high-risk recurrence preoperatively. Constructing a nomogram using the RRS system and TNM staging significantly improves the accuracy of staging and prognosis prediction, which is of great clinical significance for individualized clinical treatment and follow-up of CRC.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138048933","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":"HPV genotype-specific distribution and attributable risk in cervical intraepithelial neoplasia in a referral population with a history of LSIL.","authors":"Sam Ratnam, Dan Jang, Reza Alaghehbandan, Laura Gilbert, Yunwen Xu, Wei Wang, Phillip Andrews, Ashley Green, David J Speicher, Max Chernesky","doi":"10.3233/CBM-220470","DOIUrl":"10.3233/CBM-220470","url":null,"abstract":"<p><strong>Background and objective: </strong>CINtec PLUS and cobas HPV tests (Roche) were previously ascertained for triaging an LSIL referral population [1]. As part of this study, genotype-specific distribution and attributable risk of high-risk (HR)-HPV in cervical intraepithelial neoplasia (CIN) were determined.</p><p><strong>Methods: </strong>Archived cervical specimens in ThinPrep PreservCyt (Hologic Inc) from the LSIL referral population (n= 533) were genotyped using the Anyplex II HPV HR test (Anyplex, Seegene Inc). Since the study specimens had been in storage in ambient temperature for 31-47 months since collection, Anyplex results were compared with that of the initial cobas testing of fresh specimens to validate the suitability and stability of specimens for the present study.</p><p><strong>Results: </strong>Overall, Anyplex test was positive in 63% (336/533) vs. 55.7% (297/533) for cobas test. Anyplex test performed identical to cobas test identifying 93.2% (82/88) of ⩾CIN2/adenocarcinoma in situ (AIS). Anyplex test detected genotypes 16/18 in 15.7% (36/230) ⩽CIN1 vs. 45.5% (40/88) ⩾CIN2/AIS; the corresponding figures were 13.5% (31/230) and 45.5% (40/48) for the cobas test. Genotype 16 showed increasing attribution, 13.2% in CIN1, 27.1% in CIN2 and 40% in CIN3/AIS. Of the 12 other high-risk (OHR) types collectively identified by cobas, Anyplex test specifically detected, in decreasing order, genotypes 51, 31, 35, 56, 39, and 45 as the most frequent types, often in multiple-type infections, in 64.8% ⩾CIN2. Regardless, estimated attribution was evident for each of the 12 OHR types in ⩾CIN2. Multiple-type infections were more frequent than single-type infections in all CIN grades.</p><p><strong>Conclusions: </strong>Attributable risk of all HR-HPV genotypes targeted by both Anyplex and cobas tests was evident in ⩾CIN2/AIS Testing for these genotypes in HPV primary cervical screening and cytology triage could identify those at increased risk of cervical cancer and also be beneficial in the management of LSIL referral populations.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138048932","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":"The identification of N6-methyladenosine-related miRNAs predictive of hepatocellular carcinoma prognosis and immunotherapy efficacy.","authors":"Renrui Zou, Yaqian Liu, Sangsang Qiu, Ya Lu, Yan Chen, Hui Yu, Hangju Zhu, Wenbo Zhu, Longbiao Zhu, Jifeng Feng, Jing Han","doi":"10.3233/CBM-230263","DOIUrl":"10.3233/CBM-230263","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) has a high degree of malignancy and poor prognosis. N6-methyladenosine (m6A) modifications and microRNAs (miRNAs) play pivotal roles in tumorigenesis and development. However, the role of m6A-related miRNAs in HCC has not been clarified yet. This study aimed to identify the role of m6A-miRNAs in HCC prognosis through bioinformatics analysis.</p><p><strong>Methods: </strong>The clinicopathological information and RNA sequencing data of 369 HCC tumor tissues and 49 tumor-adjacent tissues were downloaded from the TCGA database. A total of 23 m6A regulators were extracted to evaluated the m6A-related miRNAs using Pearson's correlation analysis. Then, we selected prognosis-related m6A-miRNAs using a univariate Cox regression model and used the consensus cluster analysis to explore the characteristics of the m6A-miRNAs. The coefficient of the least absolute shrinkage and selection operator (LASSO) Cox regression was applied to construct a prognostic risk score model. The receiver operated characteristic (ROC) analysis was applied to evaluate the prognostic value of the signature. The biological functions of targeted genes were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Then, to validate the potential predictive value for prognosis, the miRNA expression profiles from the GSE76903 and GSE6857 were used. Single sample Gene Set Enrichment Analysis (ssGSEA) and Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) were applied to assess the immune microenvironment of HCC. Additionally, a meta-analysis was used to verify the prognostic value of the m6A-microRNAs. RT-PCR was applied to validated the expression of miRNAs in HCC tissues. Cell viability, transwell assay and RNA m6A dot blot assays of HCC cells was applied to access the function of miR-17-5p.</p><p><strong>Results: </strong>The expression of 48 m6A-related miRNAs was identified and 17 prognostic m6A-miRNAs was discovered. The expression profile of those 17 miRNAs was divided into three clusters, and these clusters were associated with the tumor microenvironment (TME) and prognosis. The nine m6A-related miRNA signature was associated with the prognosis of HCC, the AUC of the ROC was 0.771(TCGA dataset), 0.788(GSE76903) and 0.646(GSE6857). The TME and the expression of immune checkpoint molecules were associated with the risk score. The meta-analysis also validated the prognostic value of the m6A-related miRNAs (miR182-5p (HR:1.58, 95%CI:1.04-2.40) and miR-17-5p (HR:1.58, 95%CI: 1.04-2.40)). The expression of miR-17-5p was upregulated in HCC tissues and miR-17-5p showed an oncogenic role in HCC cells.</p><p><strong>Conclusion: </strong>The clinical innovation is the use of m6A-miRNAs as biomarkers for predicting prognosis regarding immunotherapy response in HCC patients.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441736","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":"Retraction to: miR-199a-5p suppresses epithelial- mesenchymal-transition in anaplastic thyroid carcinoma cells via targeting Snail signals.","authors":"Xuelong Jiao","doi":"10.3233/cbm-229002","DOIUrl":"https://doi.org/10.3233/cbm-229002","url":null,"abstract":"miR-199a-5p suppresses epithelialmesenchymal-transition in anaplastic thyroid carcinoma cells via targeting Snail signals Fengyun Haoa, Ya-Nan Bib, Lei Wangc, Yubing Wangc, Jilei Mac, Ping Cuic, Xuhua Lic, Shukai Sund, Liang Ninge, Yichuan Huanga, Xuelong Jiaoe,* and Dong Chene,* aDepartment of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China bOperating Room, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China cThyroid Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China dClinical Lab, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China eGeneral Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74405428","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":"Overexpression of cytoplasmic dynamin 2 is associated with worse outcomes in patients with clear cell renal cell carcinoma.","authors":"S. Safaei, Roya Sajed, Leili Saeednejad Zanjani, Mandana Rahimi, F. Fattahi, Golnaz Ensieh Kazemi-Sefat, M. Razmi, Shima Dorafshan, L. Eini, Z. Madjd, R. Ghods","doi":"10.3233/cbm-210514","DOIUrl":"https://doi.org/10.3233/cbm-210514","url":null,"abstract":"BACKGROUND\u0000Dynamin 2 (DNM2) involved in tumor progression in various malignancies.\u0000\u0000\u0000OBJECTIVE\u0000For the first time, we evaluated DNM2 expression pattern, its association with clinicopathological characteristics and survival outcomes in RCC subtypes.\u0000\u0000\u0000METHODS\u0000We evaluated the DNM2 expression pattern in RCC tissues as well as adjacent normal tissue using immunohistochemistry on tissue microarray (TMA) slides.\u0000\u0000\u0000RESULTS\u0000Our findings revealed increased DNM2 expression in RCC samples rather than in adjacent normal tissues. The results indicated that there was a statistically significant difference between cytoplasmic expression of DNM2 among subtypes of RCC in terms of intensity of staining, percentage of positive tumor cells, and H-score (P= 0.024, 0.049, and 0.009, respectively). The analysis revealed that increased cytoplasmic expression of DNM2 in ccRCC is associated with worse OS (log rank: P= 0.045), DSS (P= 0.049), and PFS (P= 0.041). Furthermore, cytoplasmic expression of DNM2 was found as an independent prognostic factor affecting DSS and PFS in multivariate analysis.\u0000\u0000\u0000CONCLUSIONS\u0000Our results indicated that DNM2 cytoplasmic expression is associated with tumor aggressiveness and poor outcomes. DNM2 could serve as a promising prognostic biomarker and therapeutic target in patients with ccRCC.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85468055","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":"Prediction of lung cancer immunotherapy response via machine learning analysis of immune cell lineage and surface markers.","authors":"Alex N. Mueller, Samantha Morrisey, Hunter A. Miller, Xiaoling Hu, Rohit Kumar, Phuong T. Ngo, Jun-Hai Yan, Hermann B. Frieboes","doi":"10.3233/cbm-210529","DOIUrl":"https://doi.org/10.3233/cbm-210529","url":null,"abstract":"BACKGROUND\u0000Although advances have been made in cancer immunotherapy, patient benefits remain elusive. For non-small cell lung cancer (NSCLC), monoclonal antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have shown survival benefit compared to chemotherapy. Personalization of treatment would be facilitated by a priori identification of patients likely to benefit.\u0000\u0000\u0000OBJECTIVE\u0000This pilot study applied a suite of machine learning methods to analyze mass cytometry data of immune cell lineage and surface markers from blood samples of a small cohort (n= 13) treated with Pembrolizumab, Atezolizumab, Durvalumab, or Nivolumab as monotherapy.\u0000\u0000\u0000METHODS\u0000Four different comparisons were evaluated between data collected at an initial visit (baseline), after 12-weeks of immunotherapy, and from healthy (control) samples: healthy vs patients at baseline, Responders vs Non-Responders at baseline, Healthy vs 12-week Responders, and Responders vs Non-Responders at 12-weeks. The algorithms Random Forest, Partial Least Squares Discriminant Analysis, Multi-Layer Perceptron, and Elastic Net were applied to find features differentiating between these groups and provide for the capability to predict outcomes.\u0000\u0000\u0000RESULTS\u0000Particular combinations and proportions of immune cell lineage and surface markers were sufficient to accurately discriminate between the groups without overfitting the data. In particular, markers associated with the B-cell phenotype were identified as key features.\u0000\u0000\u0000CONCLUSIONS\u0000This study illustrates a comprehensive machine learning analysis of circulating immune cell characteristics of NSCLC patients with the potential to predict response to immunotherapy. Upon further evaluation in a larger cohort, the proposed methodology could help guide personalized treatment selection in clinical practice.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90826420","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":"MicroRNA-204/CREB5 axis regulates vasculogenic mimicry in breast cancer cells.","authors":"Estefanía Contreras-Sanzón, C. Palma-Flores, Ali Flores-Pérez, Yarely M. Salinas-Vera, Macrina B. Silva-Cázares, Laurence A. Marchat, Rodolfo G. Avila-Bonilla, Olga N. Hernández de la Cruz, María E. Álvarez-Sánchez, C. Pérez-Plasencia, Alma D. Campos-Parra, C. López-Camarillo","doi":"10.3233/cbm-210457","DOIUrl":"https://doi.org/10.3233/cbm-210457","url":null,"abstract":"BACKGROUND\u0000Vasculogenic mimicry (VM) is characterized by formation of three-dimensional (3D) channels-like structures by tumor cells, supplying the nutrients needed for tumor growth. VM is stimulated by hypoxic tumor microenvironment, and it has been associated with increased metastasis and clinical poor outcome in cancer patients. cAMP responsive element (CRE)-binding protein 5 (CREB5) is a hypoxia-activated transcription factor involved in tumorigenesis. However, CREB5 functions in VM and if its regulated by microRNAs remains unknown in breast cancer.\u0000\u0000\u0000OBJECTIVE\u0000We aim to study the functional relationships between VM, CREB5 and microRNA-204-5p (miR-204) in breast cancer cells.\u0000\u0000\u0000METHODS\u0000CREB5 expression was evaluated by mining the public databases, and using RT-qPCR and Western blot assays. CREB5 expression was silenced using short-hairpin RNAs in MDA-MB-231 and MCF-7 breast cancer cells. VM formation was analyzed using matrigel-based cultures in hypoxic conditions. MiR-204 expression was restored in cancer cells by transfection of RNA mimics. Luciferase reporter assays were performed to evaluate the binding of miR-204 to 3'UTR of CREB5.\u0000\u0000\u0000RESULTS\u0000Our data showed that CREB5 mRNA expression was upregulated in a set of breast cancer cell lines and clinical tumors, and it was positively associated with poor prognosis in lymph nodes positive and grade 3 basal breast cancer patients. Silencing of CREB5 impaired the hypoxia-induced formation of 3D channels-like structures representative of the early stages of VM in MDA-MB-231 cells. In contrast, VM formation was not observed in MCF-7 cells. Interestingly, we found that CREB5 expression was negatively regulated by miR-204 mimics in breast cancer cells. Functional analysis confirmed that miR-204 binds to CREB5 3'-UTR indicating that it's an ulterior effector.\u0000\u0000\u0000CONCLUSIONS\u0000Our findings suggested that CREB5 could be a potential biomarker of disease progression in basal subtype of breast cancer, and that perturbations of the miR-204/CREB5 axis plays an important role in VM development in breast cancer cells.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80559674","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":"Retinol dehydrogenase 10 contributes to cancer stemness and intracellular carbohydrate storage in ovarian clear cell carcinomas.","authors":"Atsushi Murakami, T. Amano, Fumi Yoshino, H. Kita, S. Moritani, T. Murakami, T. Chano","doi":"10.3233/CBM-210435","DOIUrl":"https://doi.org/10.3233/CBM-210435","url":null,"abstract":"BACKGROUND\u0000Ovarian clear cell carcinomas (OCCCs) have been recurrent and refractory among the present treatments, so novel therapeutics are urgently needed.\u0000\u0000\u0000OBJECTIVE\u0000The present study accumulates the proof of concept to examine the feasibility of RDH10 as a therapeutic target for treating OCCCs.\u0000\u0000\u0000METHODS\u0000Immunohistochemically, RDH10 expression was evaluated in 111 primary epithelial ovarian cancers, including 55 OCCCs, 31 ovarian endometrioid carcinomas and 25 ovarian serous carcinomas. The spherogenecity provoked by RDH10 was evaluated in OCCC cells. To analyze whether RDH10 promotes carbohydrate storage via the vitamin A-gluconeogenesis pathway, phosphoenolpyruvate carboxykinase 1 (PCK1) protein levels and intracellular carbohydrate content were measured in response to modified RDH10 expression.\u0000\u0000\u0000RESULTS\u0000Abundant RDH10 was expressed specifically in OCCCs. RDH10 promoted spherogenecity and intracellular carbohydrate storage via modulation of PCK1 expression in OCCC cells.\u0000\u0000\u0000CONCLUSIONS\u0000In the present study, abundant RDH10 contributed to cancer cell stemness and intracellular carbohydrate storage in OCCCs. RDH10 is a potentially, new therapeutic candidate for treating OCCC cases.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79438879","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}