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Qiu S, Li Y, Zhang Z, Li C, Wang H, Chen A, Yan Z, Liu Y, Li Z, Huang H, Liu Y, Seow Y, Chen R, Guo J, Wen S, Tian J, Zhang H, Liu R, Han G, Wang B, Wang Y, Niu Y, Yin H. Differentiation of high risk prostate cancer with a facile urinary exosome detection workflow. iScience 2025; 28:111896. [PMID: 39995874 PMCID: PMC11848465 DOI: 10.1016/j.isci.2025.111896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 12/23/2024] [Accepted: 01/22/2025] [Indexed: 02/26/2025] Open
Abstract
Clear differentiation of high-grade and clinically insignificant prostate cancer (PCa) is critical for clinical decision-making. Here, we developed a proprietary urinary exosome isolation approach (EVLatch) and established a facile diagnostic workflow. We discovered that EEF1A1 levels, abundantly expressed on urinary exosomes, positively correlate to urinary exosome counts irrespective of source and collection time and demonstrated that EEF1A1 enables in-assay quantification of urinary exosomes. Importantly, a prostate cancer urinary EVLatch-based artificial intelligence diagnostics (PURE-AID) classification system utilizing PCA3, HOXC6, and DLX1 as targets with SPDEF for reference and EEF1A1 for quality checking, trained on 271 patients, achieved an area under the receiver operating characteristic curve (AUROC) of 0.76 in the test set of 351 patients. Combination of PURE-AID with prostate-specific antigen (PSA) and age increases AUROC to 0.80 and reduces 54.3% of unnecessary biopsies with 86.8% sensitivity. Our study provides a new classification system for differentiating high-grade PCa in a workflow- and patient-friendly manner.
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Affiliation(s)
- Shuai Qiu
- State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Medical Technology & School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Yue Li
- State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Medical Technology & School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Zheng Zhang
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China
| | - Chunchang Li
- Department of Urology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Haoyu Wang
- Department of Urology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Ao Chen
- State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Medical Technology & School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Zhi Yan
- State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Medical Technology & School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Yang Liu
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China
| | - Zifei Li
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China
| | - Hua Huang
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China
| | - Yi Liu
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
| | - Yiqi Seow
- Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A∗STAR), Singapore 138673, Republic of Singapore
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore 138673, Republic of Singapore
| | - Ruibing Chen
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
| | - Jinhong Guo
- School of Sensing Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Simeng Wen
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China
| | - Jing Tian
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China
| | - Hongtuan Zhang
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China
| | - Ranlu Liu
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China
| | - Gang Han
- State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Medical Technology & School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Baolong Wang
- Department of Urology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Yong Wang
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China
| | - Yuanjie Niu
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China
| | - HaiFang Yin
- State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Medical Technology & School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
- China Department of Clinical Laboratory, Tianjin Medical University General Hospital, Tianjin 300052, China
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Olson P, Wagner J. Established and emerging liquid biomarkers for prostate cancer detection: A review. Urol Oncol 2025; 43:3-14. [PMID: 38871601 DOI: 10.1016/j.urolonc.2024.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 03/03/2024] [Accepted: 05/18/2024] [Indexed: 06/15/2024]
Abstract
Prostate cancer remains one of the most frequently diagnosed cancers among men in the world today. Since its introduction in 1987 and FDA approval in 1994, prostate specific antigen (PSA) has reduced prostate cancer specific mortality considerably. However, the positive and negative predictive value of PSA is less than ideal and can lead to the over-detection of clinically insignificant prostate cancer. In the search for better screening measures to identify this cohort, liquid biomarkers for prostate cancer have emerged. In this review we will explore the commonly used urine and blood based prostate cancer liquid biomarkers. We detail the mechanism of each test and the validation studies that underscore their efficacy. Additionally, we will examine each test's effect on shared decision making as well as their cost efficacy in clinical practice.
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Affiliation(s)
- Philip Olson
- Division of Urology, University of Connecticut Health Center, Farmington, CT.
| | - Joseph Wagner
- Urology Division, Hartford Healthcare Medical Group, Hartford Hospital, Hartford, CT
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Liu Y, Hatano K, Nonomura N. Liquid Biomarkers in Prostate Cancer Diagnosis: Current Status and Emerging Prospects. World J Mens Health 2025; 43:8-27. [PMID: 38772530 PMCID: PMC11704174 DOI: 10.5534/wjmh.230386] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 01/12/2024] [Accepted: 01/22/2024] [Indexed: 05/23/2024] Open
Abstract
Prostate cancer (PCa) is a major health concern that necessitates appropriate diagnostic approaches for timely intervention. This review critically evaluates the role of liquid biopsy techniques, focusing on blood- and urine-based biomarkers, in overcoming the limitations of conventional diagnostic methods. The 4Kscore test and Prostate Health Index have demonstrated efficacy in distinguishing PCa from benign conditions. Urinary biomarker tests such as PCa antigen 3, MyProstateScore, SelectMDx, and ExoDx Prostate IntelliScore test have revolutionized risk stratification and minimized unnecessary biopsies. Emerging biomarkers, including non-coding RNAs, circulating tumor DNA, and prostate-specific antigen (PSA) glycosylation, offer valuable insights into PCa biology, enabling personalized treatment strategies. Advancements in non-invasive liquid biomarkers for PCa diagnosis may facilitate the stratification of patients and avoid unnecessary biopsies, particularly when PSA is in the gray area of 4 to 10 ng/mL.
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Affiliation(s)
- Yutong Liu
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Koji Hatano
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
| | - Norio Nonomura
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
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Han S, Wang M, Wang Y, Wu J, Guo Z, Wang H, Liu R, Qiu X, Hu L, Bi J, Yan W, An H, Zhang G, Zhi Y, Chen Z, Chen L, Liu L, Cheng H, Zhu S, Wang M, Zhang Y, Liu X, Lou F, Cao S, Ye D, Niu Y, Xing N. Development and validation of the utLIFE-PC algorithm for noninvasive detection of prostate cancer in urine: A prospective, observational study. Cell Rep Med 2024; 5:101870. [PMID: 39657665 PMCID: PMC11722088 DOI: 10.1016/j.xcrm.2024.101870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 03/20/2024] [Accepted: 11/18/2024] [Indexed: 12/12/2024]
Abstract
Overbiopsy is a serious health issue in prostate cancer (PCa) diagnostics. We have developed a urine tumor DNA multidimensional bioinformatic algorithm, utLIFE, to avoid unnecessary biopsy. The objective is to recognize all or clinically significant PCa. Of the 801 participants recruited in our study, 630 are selected for subsequent analysis. In the training cohort (n = 237), utLIFE-PC gets an area under the receiver operating characteristic curve (AUC) of 0.967 and a sensitivity of 85.57% at 95% specificity. In the independent prospective validation cohort (n = 343), utLIFE-PC has an AUC of 0.929, sensitivity of 84.24%, and specificity of 93.26%. Notably, in patients with ≥grade group (GG)2 and ≥GG3, the assay's sensitivity is still excellent (85.33% and 87.10%, respectively). The model shows better performance than prostate-specific antigen (PSA) (p < 0.001) or the single-dimensional biomarkers (methylation, p < 0.001; copy-number variations [CNVs], p < 0.001; mutation, p < 0.001). The utLIFE-PC model can potentially optimize the PCa diagnostic process and avoid unnecessary biopsies. This study was registered at Chinese Clinical Trial Registry: ChiCTR2300071837.
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Affiliation(s)
- Sujun Han
- Department of Urology and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mingshuai Wang
- Department of Urology and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yong Wang
- Department of Urology, The Second Affiliated Hospital of Tianjin Medical University, Tianjin, China
| | - Junlong Wu
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhaoxia Guo
- Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China
| | - Huina Wang
- Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China
| | - Ranlu Liu
- Department of Urology, The Second Affiliated Hospital of Tianjin Medical University, Tianjin, China
| | - Xiaofu Qiu
- Department of Urology, Guangdong Second Provincial General Hospital, Guangzhou, China
| | - Linjun Hu
- Department of Urology, Cancer Hospital of HuanXing, Chaoyang District Beijing, Beijing, China
| | - Jianbin Bi
- Department of Urology, China Medical University, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Weigang Yan
- Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Hengqing An
- Department of Urology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, China
| | - Gejun Zhang
- Department of Urology, China Medical University, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yi Zhi
- Department of Urology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhiyuan Chen
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Libin Chen
- Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China
| | - Lei Liu
- Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China
| | - Huanqing Cheng
- Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China
| | - Shuaipeng Zhu
- Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China
| | - Meng Wang
- Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China
| | - Yanrui Zhang
- Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China
| | - Xiao Liu
- Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China
| | - Feng Lou
- Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China.
| | - Shanbo Cao
- Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China.
| | - Dingwei Ye
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
| | - Yuanjie Niu
- Department of Urology, The Second Affiliated Hospital of Tianjin Medical University, Tianjin, China.
| | - Nianzeng Xing
- Department of Urology and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Urology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
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Luo X, Luo B, Fei L, Zhang Q, Liang X, Chen Y, Zhou X. MS4A superfamily molecules in tumors, Alzheimer's and autoimmune diseases. Front Immunol 2024; 15:1481494. [PMID: 39717774 PMCID: PMC11663944 DOI: 10.3389/fimmu.2024.1481494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 11/12/2024] [Indexed: 12/25/2024] Open
Abstract
MS4A (membrane-spanning 4-domain, subfamily A) molecules are categorized into tetraspanins, which possess four-transmembrane structures. To date, eighteen MS4A members have been identified in humans, whereas twenty-three different molecules have been identified in mice. MS4A proteins are selectively expressed on the surfaces of various immune cells, such as B cells (MS4A1), mast cells (MS4A2), macrophages (MS4A4A), Foxp3+CD4+ regulatory T cells (MS4A4B), and type 3 innate lymphoid cells (TMEM176A and TMEM176B). Early research confirmed that most MS4A molecules function as ion channels that regulate the transport of calcium ions. Recent studies have revealed that some MS4A proteins also function as chaperones that interact with various immune molecules, such as pattern recognition receptors and/or immunoglobulin receptors, to form immune complexes and transmit downstream signals, leading to cell activation, growth, and development. Evidence from preclinical animal models and human genetic studies suggests that the MS4A superfamily plays critical roles in the pathogenesis of various diseases, including cancer, infection, allergies, neurodegenerative diseases and autoimmune diseases. We review recent progress in this field and focus on elucidating the molecular mechanisms by which different MS4A molecules regulate the progression of tumors, Alzheimer's disease, and autoimmune diseases. Therefore, in-depth research into MS4A superfamily members may clarify their ability to act as candidate biomarkers and therapeutic targets for these diseases. Eighteen distinct members of the MS4A (membrane-spanning four-domain subfamily A) superfamily of four-transmembrane proteins have been identified in humans, whereas the MS4A genes are translated into twenty-three different molecules in mice. These proteins are selectively expressed on the surface of various immune cells, such as B cells (MS4A1), macrophages (MS4A4A), mast cells (MS4A2), Foxp3+CD4+ regulatory T cells (MS4A4B), type 3 innate lymphoid cells (TMEM176A and TMEM176B) and colonic epithelial cells (MS4A12). Functionally, most MS4A molecules function as ion channels that regulate the flow of calcium ions [Ca2+] across cell membranes. Recent studies have revealed that some MS4A proteins also act as molecular chaperones and interact with various types of immune receptors, including pattern recognition receptors (PRRs) and immunoglobulin receptors (IgRs), to form signaling complexes, thereby modulating intracellular signaling and cellular activity. Evidence from preclinical animal models and human genetic studies suggests that MS4A proteins play critical roles in various diseases (2). Therefore, we reviewed the recent progress in understanding the role of the MS4A superfamily in diseases, particularly in elucidating its function as a candidate biomarker and therapeutic target for cancer.
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Affiliation(s)
- Xuejiao Luo
- Department of Dermatology, The Affiliated Hospital of the Non-Commissioned Officer (NCO) School, The Army Medical University, Shijiazhuang, Hebei, China
| | - Bin Luo
- Institute of Immunology, Department of Basic Medicine, The Army Military Medical University, Chongqing, China
| | - Lei Fei
- Institute of Immunology, Department of Basic Medicine, The Army Military Medical University, Chongqing, China
| | - Qinggao Zhang
- Chronic Disease Research Center, Medical College, Dalian University, Dalian, Liaoning, China
| | - Xinyu Liang
- Department of Otolaryngology, The Second Affiliated Hospital of the Army Military Medical University, Chongqing, China
| | - Yongwen Chen
- Institute of Immunology, Department of Basic Medicine, The Army Military Medical University, Chongqing, China
- Chronic Disease Research Center, Medical College, Dalian University, Dalian, Liaoning, China
| | - Xueqin Zhou
- Department of Otolaryngology, The Second Affiliated Hospital of the Army Military Medical University, Chongqing, China
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Wilson TK, Zishiri OT. Prostate Cancer: A Review of Genetics, Current Biomarkers and Personalised Treatments. Cancer Rep (Hoboken) 2024; 7:e70016. [PMID: 39410867 PMCID: PMC11480670 DOI: 10.1002/cnr2.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 08/22/2024] [Accepted: 09/09/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND Prostate cancer is the second leading cause of cancer deaths in men, second only to lung cancer. Despite this, diagnosis and prognosis methods remain limited, with effective treatments being few and far between. Traditionally, prostate cancer is initially tested for through a prostate serum antigen (PSA) test and a digital rectum examination (DRE), followed by confirmation through an invasive prostate biopsy. The DRE and biopsy are uncomfortable for the patient, so less invasive, accurate diagnostic tools are needed. Current diagnostic tools, along with genes that hold possible biomarker uses in diagnosis, prognosis and indications for personalised treatment plans, were reviewed in this article. RECENT FINDINGS Several genes from multiple families have been identified as possible biomarkers for disease, including those from the MYC and ETS families, as well as several tumour suppressor genes, Androgen Receptor signalling genes and DNA repair genes. There have also been advances in diagnostic tools, including MRI-targeted and liquid biopsies. Several personalised treatments have been developed over the years, including those that target metabolism-driven prostate cancer or those that target inflammation-driven cancer. CONCLUSION Several advances have been made in prostate cancer diagnosis and treatment, but the disease still grows year by year, leading to more and more deaths annually. This calls for even more research into this disease, allowing for better diagnosis and treatment methods and a better chance of patient survival.
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Affiliation(s)
- Trevor K. Wilson
- Discipline of Genetics, School of Life Sciences, College of Agriculture, Engineering, and ScienceUniversity of KwaZulu‐NatalDurbanSouth Africa
| | - Oliver T. Zishiri
- Discipline of Genetics, School of Life Sciences, College of Agriculture, Engineering, and ScienceUniversity of KwaZulu‐NatalDurbanSouth Africa
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Stella M, Russo GI, Leonardi R, Carcò D, Gattuso G, Falzone L, Ferrara C, Caponnetto A, Battaglia R, Libra M, Barbagallo D, Di Pietro C, Pernagallo S, Barbagallo C, Ragusa M. Extracellular RNAs from Whole Urine to Distinguish Prostate Cancer from Benign Prostatic Hyperplasia. Int J Mol Sci 2024; 25:10079. [PMID: 39337566 PMCID: PMC11432375 DOI: 10.3390/ijms251810079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/13/2024] [Accepted: 09/17/2024] [Indexed: 09/30/2024] Open
Abstract
RNAs, especially non-coding RNAs (ncRNAs), are crucial players in regulating cellular mechanisms due to their ability to interact with and regulate other molecules. Altered expression patterns of ncRNAs have been observed in prostate cancer (PCa), contributing to the disease's initiation, progression, and treatment response. This study aimed to evaluate the ability of a specific set of RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), and mRNAs, to discriminate between PCa and the non-neoplastic condition benign prostatic hyperplasia (BPH). After selecting by literature mining the most relevant RNAs differentially expressed in biofluids from PCa patients, we evaluated their discriminatory power in samples of unfiltered urine from 50 PCa and 50 BPH patients using both real-time PCR and droplet digital PCR (ddPCR). Additionally, we also optimized a protocol for urine sample manipulation and RNA extraction. This two-way validation study allowed us to establish that miRNAs (i.e., miR-27b-3p, miR-574-3p, miR-30a-5p, and miR-125b-5p) are more efficient biomarkers for PCa compared to long RNAs (mRNAs and lncRNAs) (e.g., PCA3, PCAT18, and KLK3), as their dysregulation was consistently reported in the whole urine of patients with PCa compared to those with BPH in a statistically significant manner regardless of the quantification methodology performed. Moreover, a significant increase in diagnostic performance was observed when molecular signatures composed of different miRNAs were considered. Hence, the abovementioned circulating ncRNAs represent excellent potential non-invasive biomarkers in urine capable of effectively distinguishing individuals with PCa from those with BPH, potentially reducing cancer overdiagnosis.
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Affiliation(s)
- Michele Stella
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics "G. Sichel", University of Catania, 95123 Catania, Italy
| | - Giorgio Ivan Russo
- Department of Urology, Polyclinic Hospital, University of Catania, 95123 Catania, Italy
| | - Rosario Leonardi
- Casa di Cura Musumeci GECAS, 95030 Gravina di Catania, Italy
- Department of Medicine and Surgery, University of Enna KORE, 94100 Enna, Italy
| | - Daniela Carcò
- Istituto Oncologico del Mediterraneo, 95029 Viagrande, Italy
| | - Giuseppe Gattuso
- Department of Biomedical and Biotechnological Sciences, Oncologic, Clinical and General Pathology Section, University of Catania, 95123 Catania, Italy
| | - Luca Falzone
- Department of Biomedical and Biotechnological Sciences, Oncologic, Clinical and General Pathology Section, University of Catania, 95123 Catania, Italy
| | - Carmen Ferrara
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics "G. Sichel", University of Catania, 95123 Catania, Italy
| | - Angela Caponnetto
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics "G. Sichel", University of Catania, 95123 Catania, Italy
| | - Rosalia Battaglia
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics "G. Sichel", University of Catania, 95123 Catania, Italy
| | - Massimo Libra
- Department of Biomedical and Biotechnological Sciences, Oncologic, Clinical and General Pathology Section, University of Catania, 95123 Catania, Italy
| | - Davide Barbagallo
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics "G. Sichel", University of Catania, 95123 Catania, Italy
| | - Cinzia Di Pietro
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics "G. Sichel", University of Catania, 95123 Catania, Italy
| | - Salvatore Pernagallo
- DESTINA Genomica S.L., Health Sciences Technology Park (PTS), Av. de la Innovación 1, Building Business Innovation Center (BIC), 18016 Granada, Spain
| | - Cristina Barbagallo
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics "G. Sichel", University of Catania, 95123 Catania, Italy
| | - Marco Ragusa
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics "G. Sichel", University of Catania, 95123 Catania, Italy
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Kawada T, Shim SR, Quhal F, Rajwa P, Pradere B, Yanagisawa T, Bekku K, Laukhtina E, von Deimling M, Teoh JYC, Karakiewicz PI, Araki M, Shariat SF. Diagnostic Accuracy of Liquid Biomarkers for Clinically Significant Prostate Cancer Detection: A Systematic Review and Diagnostic Meta-analysis of Multiple Thresholds. Eur Urol Oncol 2024; 7:649-662. [PMID: 37981495 DOI: 10.1016/j.euo.2023.10.029] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 10/21/2023] [Accepted: 10/31/2023] [Indexed: 11/21/2023]
Abstract
CONTEXT Many liquid biomarkers have entered clinical practice with the praise to improve the detection of clinically significant prostate cancer (csPCa), helping avoid unnecessary prostate biopsies. OBJECTIVE We aimed to assess the diagnostic accuracy of multianalyte biomarkers for csPCa detection using multiple thresholds. EVIDENCE ACQUISITION A comprehensive literature search was done through PubMed, Web of Science, and Scopus in March 2023 for prospective and retrospective studies reporting the diagnostic performance of liquid biomarkers for detecting csPCa. The outcomes of interest were the diagnostic performance of liquid biomarkers for csPCa detection and identification of optimal thresholds for each biomarker. EVIDENCE SYNTHESIS Overall, 49 studies were eligible for this meta-analysis. Using each representative threshold based on the Youden Index, the pooled sensitivity and specificity for detecting csPCa were 0.85 and 0.37 for prostate cancer gene 3 (PCA3), 0.85 and 0.52 for prostate health index (PHI), 0.87 and 0.58 for four kallikrein (4K), 0.82 and 0.56 for SelectMDx, 0.85 and 0.54 for ExoDx, and 0.82 and 0.59 for mi prostate score (MPS), respectively. The diagnostic odds ratio was highest for 4K (8.84), followed by MPS (7.0) and PHI (6.28). According to the meta-analysis incorporating multiple thresholds, the corresponding sensitivity was 0.77 for 4K, 0.69 for PHI, and 0.63 for PCA3; specificity was 0.72 for PHI, 0.70 for 4K, and 0.69 for PCA3. CONCLUSIONS Regarding the detection of csPCa, 4K had the highest diagnostic performance among the commercial liquid biomarkers. Based on the optimal thresholds calculated by the present meta-analysis, 4K had the highest sensitivity and PHI had the highest specificity for detecting csPCa. Nevertheless, clinical decision-making requires combination strategies between liquid and imaging biomarkers. PATIENT SUMMARY Novel biomarkers for prostate cancer detection were useful for more accurate diagnosis of clinically significant prostate cancer to avoid unnecessary biopsies.
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Affiliation(s)
- Tatsushi Kawada
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Sung Ryul Shim
- Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Fahad Quhal
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Pawel Rajwa
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Medical University of Silesia, Zabrze, Poland
| | - Benjamin Pradere
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology UROSUD, La Croix Du Sud Hospital, Quint Fonsegrives, France
| | - Takafumi Yanagisawa
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Kensuke Bekku
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Ekaterina Laukhtina
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia
| | - Markus von Deimling
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jeremy Yuen-Chun Teoh
- S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China
| | - Pierre I Karakiewicz
- Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada
| | - Motoo Araki
- Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shahrokh F Shariat
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Hourani Center for Applied Scientific Research, AI-Ahliyya Amman University, Amman, Jordan; Research Center for Evidence-Based Medicine, Iranian EBM Center: A Joanna Briggs Institute Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran.
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9
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Kumar AA. Prostate cancer genotyping for risk stratification and precision treatment. Curr Urol 2024; 18:87-97. [PMID: 39176294 PMCID: PMC11337998 DOI: 10.1097/cu9.0000000000000222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 05/30/2023] [Indexed: 08/24/2024] Open
Abstract
Prostate cancer (PC) is the most frequently diagnosed cancer and second leading cause of cancer-related deaths in men. It is heterogeneous, as is evident from the wide spectrum of therapeutic approaches. Most patients with PC are initially responsive to androgen deprivation therapy; however, the majority of cases are either hormone-sensitive PC or castration-resistant PC. Current therapeutic protocols follow the evolution of PC, a continuously progressive process involving a combination of widespread genomic alterations. These genomic alterations are either hereditary germline mutations, such as mutations in BRCA2, or specific only to tumor cells (somatic). Tumor-specific genomic spectra include genomic structural rearrangements, canonical androgen response genes, and many other specific genes such as TMPRSS2-ERG fusion, SPOP/FOXA1, TP53/RB1/PTEN, and BRCA2. New evidence indicates the involvement of signaling pathways including PI3K, WNT/β-catenin, SRC, and IL-6/STAT, which have been shown to promote epithelial-mesenchymal transition cancer stem cell-like features/stemness, and neuroendocrine differentiation in PC. Over the last decade, our understanding of the genotype-phenotype relationships has been enhanced considerably. The genetic background of PC related to canonical genetic alterations and signaling pathway activation genes has shed more insight into the molecular subtype and disease landscape, resulting in a more flexible role of individual therapies targeting diverse genotypes and phenotypes.
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Affiliation(s)
- Ashish A. Kumar
- Department of Urology, York & Scarborough Teaching Hospitals NHS Foundation Trust, York, UK
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10
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Lawisch GKDS, Dexheimer GM, Biolchi V, Seewald RA, Chies JAB. Prostate tumor markers: diagnosis, prognosis and management. Genet Mol Biol 2024; 46:e20230136. [PMID: 38407310 PMCID: PMC10895695 DOI: 10.1590/1678-4685-gmb-2023-0136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 01/17/2024] [Indexed: 02/27/2024] Open
Abstract
Prostate cancer (PCA) is the second most common type of cancer in the world. Nevertheless, diagnosis is still based on nonspecific methods, or invasive methods which makes clinical decision and diagnosis difficult, generating risk of both underdiagnosis and overdiagnosis. Given the high prevalence, morbidity and mortality of PCA, new strategies are needed for its diagnosis. A review of the literature on available biomarkers for PCA was performed, using the following terms: prostate cancer AND marker OR biomarker. The search was carried out in Pubmed, Science Direct, Web of Science and Clinical Trial. A total of 35 articles were used, and PHI (Prostate Health Index) and the 4Kscore tests were identified as the best well-established serum markers. These tests are based on the evaluation of expression levels of several molecules. For analysis of urine samples, Progensa, ExoDXProstate, and Mi Prostate Score Urine Test are available. All these tests have the potential to help diagnosis, avoiding unnecessary biopsies, but they are used only in association with digital rectal examination and PSA level data. The search for biomarkers that can help in the diagnosis and therapeutic management of PCA is still in its initial phase, requiring more efforts for an effective clinical application.
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Affiliation(s)
- Gabriela Kniphoff da Silva Lawisch
- Universidade do Vale do Taquari (Univates), Lajeado, RS, Brasil
- Universidade Federal do Rio Grande do Sul, Departamento de Genética, Programa de Pós-Graduação em Genética e Biologia Molecular, Porto Alegre, RS, Brasil
| | | | | | - Rafael Armando Seewald
- Universidade do Vale do Taquari (Univates), Lajeado, RS, Brasil
- Hospital Bruno Born, Centro de Oncologia, Lajeado, RS, Brasil
| | - José Artur Bogo Chies
- Universidade Federal do Rio Grande do Sul, Departamento de Genética, Programa de Pós-Graduação em Genética e Biologia Molecular, Porto Alegre, RS, Brasil
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11
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Jain S, Malhotra KPK, Patiyal S, Raghava GPS. A Highly Accurate Model for Screening Prostate Cancer Using Propensity Index Panel of Ten Genes. J Comput Biol 2023; 30:1305-1314. [PMID: 37917795 DOI: 10.1089/cmb.2023.0040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2023] Open
Affiliation(s)
- Shipra Jain
- Department of Computational Biology, Indraprastha Institute of Information Technology, Delhi, New Delhi, India
| | - Kawal Preet Kaur Malhotra
- Department of Computational Biology, Indraprastha Institute of Information Technology, Delhi, New Delhi, India
| | - Sumeet Patiyal
- Department of Computational Biology, Indraprastha Institute of Information Technology, Delhi, New Delhi, India
| | - Gajendra Pal Singh Raghava
- Department of Computational Biology, Indraprastha Institute of Information Technology, Delhi, New Delhi, India
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12
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Huang HP, Chen CH, Chang KH, Lee MS, Lee CF, Chao YH, Lu SY, Wu TF, Liang ST, Lin CY, Lin YC, Liu SP, Lu YC, Shun CT, Huang WJ, Lin TP, Ku MH, Chung HJ, Chang YH, Liao CH, Yu CC, Chung SD, Tsai YC, Wu CC, Chen KC, Ho CH, Hsiao PW, Pu YS. Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study. J Transl Med 2023; 21:714. [PMID: 37821919 PMCID: PMC10566053 DOI: 10.1186/s12967-023-04424-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 08/07/2023] [Indexed: 10/13/2023] Open
Abstract
PURPOSE Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk. METHODS Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC). RESULTS In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS. CONCLUSION This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.
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Affiliation(s)
- Hsiang-Po Huang
- Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chung-Hsin Chen
- Department of Urology, National Taiwan University College of Medicine and Hospital, 7 Zhongshan South Road, Taipei, 100225, Taiwan, Republic of China
| | - Kai-Hsiung Chang
- Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan
| | - Ming-Shyue Lee
- Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Cheng-Fan Lee
- Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yen-Hsiang Chao
- Department of Urology, National Taiwan University College of Medicine and Hospital, 7 Zhongshan South Road, Taipei, 100225, Taiwan, Republic of China
| | - Shih-Yu Lu
- Department of Urology, National Taiwan University College of Medicine and Hospital, 7 Zhongshan South Road, Taipei, 100225, Taiwan, Republic of China
| | - Tzu-Fan Wu
- Department of Urology, National Taiwan University College of Medicine and Hospital, 7 Zhongshan South Road, Taipei, 100225, Taiwan, Republic of China
| | - Sung-Tzu Liang
- Department of Urology, National Taiwan University College of Medicine and Hospital, 7 Zhongshan South Road, Taipei, 100225, Taiwan, Republic of China
| | - Chih-Yu Lin
- Agricultural Biotechnology Research Center, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei, 11529, Taiwan
| | - Yuan Chi Lin
- Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Shih-Ping Liu
- Department of Urology, National Taiwan University College of Medicine and Hospital, 7 Zhongshan South Road, Taipei, 100225, Taiwan, Republic of China
| | - Yu-Chuan Lu
- Department of Urology, National Taiwan University College of Medicine and Hospital, 7 Zhongshan South Road, Taipei, 100225, Taiwan, Republic of China
- Department of Surgical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - William J Huang
- Department of Urology, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tzu-Ping Lin
- Department of Urology, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ming-Hsuan Ku
- Department of Urology, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Hsiao-Jen Chung
- Department of Urology, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yen-Hwa Chang
- Department of Urology, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Hou Liao
- Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City, Taiwan
- School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chih-Chin Yu
- Division of Urology, Department of Surgery, Taipei Tzu Chi Hospital, and the Buddhist Tzu Chi Medical Foundation, College of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Shiu-Dong Chung
- Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, and Department of Nursing, College of Healthcare & Management, Asia Eastern University of Science and Technology, New Taipei City, Taiwan
| | - Yao-Chou Tsai
- Department of Medicine & Division of Urology, Taipei Tzu Chi Hospital, New Taipei City, Taiwan
| | - Chia-Chang Wu
- Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Department of Urology, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
| | - Kuan-Chou Chen
- Department of Urology, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chen-Hsun Ho
- School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
- Division of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Pei-Wen Hsiao
- Agricultural Biotechnology Research Center, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei, 11529, Taiwan.
| | - Yeong-Shiau Pu
- Department of Urology, National Taiwan University College of Medicine and Hospital, 7 Zhongshan South Road, Taipei, 100225, Taiwan, Republic of China.
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13
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Ferro M, Rocco B, Maggi M, Lucarelli G, Falagario UG, Del Giudice F, Crocetto F, Barone B, La Civita E, Lasorsa F, Brescia A, Catellani M, Busetto GM, Tataru OS, Terracciano D. Beyond blood biomarkers: the role of SelectMDX in clinically significant prostate cancer identification. Expert Rev Mol Diagn 2023; 23:1061-1070. [PMID: 37897252 DOI: 10.1080/14737159.2023.2277366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 10/26/2023] [Indexed: 10/30/2023]
Abstract
INTRODUCTION New potential biomarkers to pre-intervention identification of a clinically significant prostate cancer (csPCa) will prevent overdiagnosis and overtreatment and limit quality of life impairment of PCa patients. AREAS COVERED We have developed a comprehensive review focusing our research on the increasing knowledge of the role of SelectMDX® in csPCa detection. Areas identified as clinically relevant are the ability of SelectMDX® to predict csPCa in active surveillance setting, its predictive ability when combined with multiparametric MRI and the role of SelectMDX® in the landscape of urinary biomarkers. EXPERT OPINION Several PCa biomarkers have been developed either alone or in combination with clinical variables to improve csPCa detection. SelectMDX® score includes genomic markers, age, PSA, prostate volume, and digital rectal examination. Several studies have shown consistency in the ability to improve detection of csPCa, avoidance of unnecessary prostate biopsies, helpful in decision-making for clinical benefit of PCa patients with future well designed, and impactful studies.
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Affiliation(s)
- Matteo Ferro
- Department of Urology, IEO - European Institute of Oncology, IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico, via Ripamonti 435, Milan 20141, Italy
| | - Bernardo Rocco
- Unit of Urology, Department of Health Science, University of Milan, ASST Santi Paolo and Carlo, Via A. Di Rudini 8, Milan 20142, Italy
| | - Martina Maggi
- Department of Maternal Infant and Urologic Sciences, Policlinico Umberto I Hospital, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy
| | - Giuseppe Lucarelli
- Urology, Andrology and Kidney Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza Umberto I - 70121, Bari, Italy
| | - Ugo Giovanni Falagario
- Department of Urology and Organ Transplantation, University of Foggia, Via A.Gramsci 89/91, 71122 Foggia, Italy
| | - Francesco Del Giudice
- Department of Maternal Infant and Urologic Sciences, Policlinico Umberto I Hospital, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy
| | - Felice Crocetto
- Department of Neurosciences and Reproductive Sciences and Odontostomatology, University of Naples Federico II, Via Pansini, 5 - 80131, Naples, Italy
| | - Biagio Barone
- Department of Surgical Sciences, Urology Unit, AORN Sant'Anna e San Sebastiano, Caserta, Via Ferdinando Palasciano, 81100 Caserta , Italy
| | - Evelina La Civita
- Department of Translational Medical Sciences, University of Naples "Federico II", Corso Umberto I 40 - 80138 Naples, Italy
| | - Francesco Lasorsa
- Urology, Andrology and Kidney Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza Umberto I - 70121, Bari, Italy
| | - Antonio Brescia
- Department of Urology, IEO - European Institute of Oncology, IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico, via Ripamonti 435, Milan 20141, Italy
| | - Michele Catellani
- Department of Urology, IEO - European Institute of Oncology, IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico, via Ripamonti 435, Milan 20141, Italy
| | - Gian Maria Busetto
- Department of Urology and Organ Transplantation, University of Foggia, Via A.Gramsci 89/91, 71122 Foggia, Italy
| | - Octavian Sabin Tataru
- Department of Simulation Applied in Medicine, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mures, Gh Marinescu 35, 540142 Târgu Mures, Romania
| | - Daniela Terracciano
- Department of Translational Medical Sciences, University of Naples "Federico II", Corso Umberto I 40 - 80138 Naples, Italy
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14
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Jiang Q, Lei Z, Wang Z, Wang Q, Zhang Z, Liu X, Xing B, Li S, Guo X, Liu Y, Li X, Qi Y, Shu K, Zhang H, Huang Y, Lei T. Tumor-Associated Fibroblast-Derived Exosomal circDennd1b Promotes Pituitary Adenoma Progression by Modulating the miR-145-5p/ONECUT2 Axis and Activating the MAPK Pathway. Cancers (Basel) 2023; 15:3375. [PMID: 37444485 DOI: 10.3390/cancers15133375] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 06/16/2023] [Accepted: 06/23/2023] [Indexed: 07/15/2023] Open
Abstract
TAF participated in the progression of various cancers, including PA via the release of soluble factors. Exosomes belonged to extracellular vesicles, which were revealed as a crucial participator in intercellular communication. However, the expression pattern and effect of TAF-derived exosomes remained largely unknown in PA. In the present study, we performed in silico analysis based on public RNA-seq datasets to generate the circRNA/miRNA regulatory network. The qRT-PCR, Western blotting, RNA pull-down, and luciferase assay were performed to investigate the effect of TAF-derived exosomes. TAF-derived exosomal circDennd1b was significantly upregulated in PA and promoted the proliferation, migration, and invasion of PA cells via sponging miR-145-5p in PA cells. In addition, miR-145-5p directly regulated One Cut homeobox 2 (ONECUT2/OC2) expression and inhibited the promoting effect of ONECUT2 on PA. We further demonstrated that ONECUT2 transcriptionally increased fibroblast growth factor receptor 3 (FGFR3) expression, which further activates the mitogen-activated protein kinases (MAPK) pathway, thus promoting PA progression. Moreover, the suppression of TAFs by ABT-263 and ONECUT2 by CSRM617 inhibited the growth of PA. In conclusion, our study illustrated that TAF-derived exosomal circDennd1b affected PA progression via regulating ONECUT2 expression, which provides a potential therapeutic strategy against aggressive PA.
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Affiliation(s)
- Qian Jiang
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Zhuowei Lei
- Department of Orthopedics, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
| | - Zihan Wang
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Quanji Wang
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Zhuo Zhang
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Xiaojin Liu
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Biao Xing
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Sihan Li
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Xiang Guo
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yanchao Liu
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Xingbo Li
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yiwei Qi
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Kai Shu
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
| | - Huaqiu Zhang
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yimin Huang
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Ting Lei
- Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
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15
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Chen YC, Li DB, Wang DL, Peng H. Comprehensive analysis of distal-less homeobox family gene expression in colon cancer. World J Gastrointest Oncol 2023; 15:1019-1035. [PMID: 37389108 PMCID: PMC10302991 DOI: 10.4251/wjgo.v15.i6.1019] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/06/2023] [Accepted: 04/27/2023] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND The distal-less homeobox (DLX) gene family plays an important role in the development of several tumors. However, the expression pattern, prognostic and diagnostic value, possible regulatory mechanisms, and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported.
AIM We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer.
METHODS Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases. Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue. cBioPortal was used to analyze DLX gene family variants. R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map. The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family. The pROC package was used to analyze the diagnostic value of the DLX gene family. R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes. The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration. The ggplot2, the survminer package, and the clusterProfiler package were used for visualization.
RESULTS DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients. The expression of DLX genes were associated with M stage, pathologic stage, primary therapy outcome, residual tumor, lymphatic invasion, T stage, N stage, age, perineural invasion, and history of colon polyps. DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis. DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways, including the Hippo signaling pathway, the Wnt signaling pathway, several signaling pathways regulating the pluripotency of stem cells, and Staphylococcus aureus infection.
CONCLUSION The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.
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Affiliation(s)
- Yong-Cheng Chen
- Department of General Surgery (Endoscopic Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Dong-Bing Li
- Department of Medicine, ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China
| | - Dong-Liang Wang
- Department of Medicine, ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China
| | - Hui Peng
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of General Surgery (Anorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
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16
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Groen L, Kloots I, Englert D, Seto K, Estafanos L, Smith P, Verhaegh GW, Mehra N, Schalken JA. Transcriptome Profiling of Circulating Tumor Cells to Predict Clinical Outcomes in Metastatic Castration-Resistant Prostate Cancer. Int J Mol Sci 2023; 24:ijms24109002. [PMID: 37240349 DOI: 10.3390/ijms24109002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/04/2023] [Accepted: 05/16/2023] [Indexed: 05/28/2023] Open
Abstract
The clinical utility of circulating tumor cells (CTC) as a non-invasive multipurpose biomarker is broadly recognized. The earliest methods for enriching CTCs from whole blood rely on antibody-based positive selection. The prognostic utility of CTC enumeration using positive selection with the FDA-approved CellSearchTM system has been demonstrated in numerous studies. The capture of cells with specific protein phenotypes does not fully represent cancer heterogeneity and therefore does not realize the prognostic potential of CTC liquid biopsies. To avoid this selection bias, CTC enrichment based on size and deformability may provide better fidelity, i.e., facilitate the characterization of CTCs with any phenotype. In this study, the recently FDA-approved Parsortix® technology was used to enrich CTCs from prostate cancer (PCa) patients for transcriptome analysis using HyCEADTM technology. A tailored PCa gene panel allowed us to stratify metastatic castration-resistant prostate cancer (mCRPC) patients with clinical outcomes. In addition, our findings suggest that targeted CTC transcriptome profiling may be predictive of therapy response.
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Affiliation(s)
- Levi Groen
- Department of Urology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Iris Kloots
- Department of Medical Oncology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | | | - Kelly Seto
- ANGLE Biosciences Inc., Toronto, ON M9W 1B3, Canada
| | | | - Paul Smith
- ANGLE Biosciences Inc., Toronto, ON M9W 1B3, Canada
| | - Gerald W Verhaegh
- Department of Urology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Niven Mehra
- Department of Medical Oncology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Jack A Schalken
- Department of Urology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
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17
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Hu H, Yin Y, Jiang B, Feng Z, Cai T, Wu S. Cuproptosis signature and PLCD3 predicts immune infiltration and drug responses in osteosarcoma. Front Oncol 2023; 13:1156455. [PMID: 37007130 PMCID: PMC10060837 DOI: 10.3389/fonc.2023.1156455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 02/28/2023] [Indexed: 03/18/2023] Open
Abstract
Osteosarcoma (OS) is a cancer that is frequently found in children and adolescents and has made little improvement in terms of prognosis in recent years. A recently discovered type of programmed cell death called cuproptosis is mediated by copper ions and the tricarboxylic acid (TCA) cycle. The expression patterns, roles, and prognostic and predictive capabilities of the cuproptosis regulating genes were investigated in this work. TARGET and GEO provided transcriptional profiling of OS. To find different cuproptosis gene expression patterns, consensus clustering was used. To identify hub genes linked to cuproptosis, differential expression (DE) and weighted gene co-expression network analysis (WGCNA) were used. Cox regression and Random Survival Forest were used to build an evaluation model for prognosis. For various clusters/subgroups, GSVA, mRNAsi, and other immune infiltration experiments were carried out. The drug-responsive study was carried out by the Oncopredict algorithm. Cuproptosis genes displayed two unique patterns of expression, and high expression of FDX1 was associated with a poor outcome in OS patients. The TCA cycle and other tumor-promoting pathways were validated by the functional study, and activation of the cuproptosis genes may also be connected with immunosuppressive state. The robust survival prediction ability of a five-gene prognostic model was verified. This rating method also took stemness and immunosuppressive characteristics into account. Additionally, it can be associated with a higher sensitivity to medications that block PI3K/AKT/mTOR signaling as well as numerous chemoresistances. U2OS cell migration and proliferation may be encouraged by PLCD3. The relevance of PLCD3 in immunotherapy prediction was verified. The prognostic significance, expressing patterns, and functions of cuproptosis in OS were revealed in this work on a preliminary basis. The cuproptosis-related scoring model worked well for predicting prognosis and chemoresistance.
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Affiliation(s)
- Hai Hu
- Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Yuesong Yin
- Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Binbin Jiang
- Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Zhennan Feng
- Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Ting Cai
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Ting Cai, ; Song Wu,
| | - Song Wu
- Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Ting Cai, ; Song Wu,
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18
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Gene-Transcript Expression in Urine Supernatant and Urine Cell-Sediment Are Different but Equally Useful for Detecting Prostate Cancer. Cancers (Basel) 2023; 15:cancers15030789. [PMID: 36765747 PMCID: PMC9913640 DOI: 10.3390/cancers15030789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 01/19/2023] [Accepted: 01/21/2023] [Indexed: 02/02/2023] Open
Abstract
There is considerable interest in urine as a non-invasive liquid biopsy to detect prostate cancer (PCa). PCa-specific transcripts such as the TMPRSS2:ERG fusion gene can be found in both urine extracellular vesicles (EVs) and urine cell-sediment (Cell) but the relative usefulness of these and other genes in each fraction in PCa detection has not been fully elucidated. Urine samples from 76 men (PCa n = 40, non-cancer n = 36) were analysed by NanoString for 154 PCa-associated genes-probes, 11 tissue-specific, and six housekeeping. Comparison to qRT-PCR data for four genes (PCA3, OR51E2, FOLH1, and RPLP2) was strong (r = 0.51-0.95, Spearman p < 0.00001). Comparing EV to Cells, differential gene expression analysis found 57 gene-probes significantly more highly expressed in 100 ng of amplified cDNA products from the EV fraction, and 26 in Cells (p < 0.05; edgeR). Expression levels of prostate-specific genes (KLK2, KLK3) measured were ~20× higher in EVs, while PTPRC (white-blood Cells) was ~1000× higher in Cells. Boruta analysis identified 11 gene-probes as useful in detecting PCa: two were useful in both fractions (PCA3, HOXC6), five in EVs alone (GJB1, RPS10, TMPRSS2:ERG, ERG_Exons_4-5, HPN) and four from Cell (ERG_Exons_6-7, OR51E2, SPINK1, IMPDH2), suggesting that it is beneficial to fractionate whole urine prior to analysis. The five housekeeping genes were not significantly differentially expressed between PCa and non-cancer samples. Expression signatures from Cell, EV and combined data did not show evidence for one fraction providing superior information over the other.
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19
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Boehm BE, York ME, Petrovics G, Kohaar I, Chesnut GT. Biomarkers of Aggressive Prostate Cancer at Diagnosis. Int J Mol Sci 2023; 24:2185. [PMID: 36768533 PMCID: PMC9916581 DOI: 10.3390/ijms24032185] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/09/2023] [Accepted: 01/15/2023] [Indexed: 01/24/2023] Open
Abstract
In the United States, prostate cancer (CaP) remains the second leading cause of cancer deaths in men. CaP is predominantly indolent at diagnosis, with a small fraction (25-30%) representing an aggressive subtype (Gleason score 7-10) that is prone to metastatic progression. This fact, coupled with the criticism surrounding the role of prostate specific antigen in prostate cancer screening, demonstrates the current need for a biomarker(s) that can identify clinically significant CaP and avoid unnecessary biopsy procedures and psychological implications of being diagnosed with low-risk prostate cancer. Although several diagnostic biomarkers are available to clinicians, very few comparative trials have been performed to assess the clinical effectiveness of these biomarkers. It is of note, however, that a majority of these clinical trials have been over-represented by men of Caucasian origin, despite the fact that African American men have a 1.7 times higher incidence and 2.1 times higher rate of mortality from prostate cancer. Biomarkers for CaP diagnosis based on the tissue of origin include urine-based gene expression assays (PCA3, Select MDx, ExoDx Prostate IntelliScore, Mi-Prostate Score, PCA3-PCGEM1 gene panel), blood-based protein biomarkers (4K, PHI), and tissue-based DNA biomarker (Confirm MDx). Another potential direction that has emerged to aid in the CaP diagnosis include multi-parametric magnetic resonance imaging (mpMRI) and bi-parametric magnetic resonance imaging (bpMRI), which in conjunction with clinically validated biomarkers may provide a better approach to predict clinically significant CaP at diagnosis. In this review, we discuss some of the adjunctive biomarker tests along with newer imaging modalities that are currently available to help clinicians decide which patients are at risk of having high-grade CaP on prostate biopsy with the emphasis on clinical utility of the tests across African American (AA) and Caucasian (CA) men.
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Affiliation(s)
- Brock E. Boehm
- Urology Service, Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
| | - Monica E. York
- School of Medicine, Uniformed Services University of Health Science, Bethesda, MD 20814, USA
| | - Gyorgy Petrovics
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Henry Jackson Foundation for the Advancement of Military Medicine (HJF), Bethesda, MD 20817, USA
| | - Indu Kohaar
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Henry Jackson Foundation for the Advancement of Military Medicine (HJF), Bethesda, MD 20817, USA
| | - Gregory T. Chesnut
- Urology Service, Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
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20
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Ma H, Zhou C, Ge J, Yu W, Zhou Y, Wang P, Zhang X, Zhang J, Shi G. Identification of molecular subtypes and a prognostic signature based on chromatin regulators related genes in prostate cancer. Front Genet 2023; 13:1110723. [PMID: 36704352 PMCID: PMC9871366 DOI: 10.3389/fgene.2022.1110723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 12/22/2022] [Indexed: 01/12/2023] Open
Abstract
The clinical and molecular phenotypes of prostate cancer (PCa) exhibit substantial heterogeneity, ranging from indolent to metastatic disease. In this study, we aimed to identify PCa subtypes and construct a gene signature that can predict the recurrence-free survival (RFS) of PCa patients based on chromatin regulators genes (CRGs). Strikingly, we identified two heterogeneous subtypes with distinct clinical and molecular characteristics. Furthermore, by performing differential analysis between the two CRGs subtypes, we successfully constructed a gene signature to predict PCa prognosis. The signature, comprising four genes (MXD3, SSTR1, AMH and PPFIA2), was utilized to classify PCa patients into two risk groups; the high-risk group was characterized by poor prognosis and more aggressive clinical features. Moreover, we investigated the immune profile, mutation landscape and molecular pathways in each of the groups. Additionally, drug-susceptibility testing was performed to explore sensitive drugs for high-risk patients. Furthermore, we found that MXD3 downregulation suppressed the proliferation of PCa cell lines in vitro. Overall, our results highlight the signature based on CRGs as a powerful tool for predicting RFS of PCa patients, as well as an indicator for personalized treatment of those patients.
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Affiliation(s)
| | | | | | | | | | | | | | - Jun Zhang
- *Correspondence: Jun Zhang, ; Guowei Shi,
| | - Guowei Shi
- *Correspondence: Jun Zhang, ; Guowei Shi,
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21
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del Pino-Sedeño T, Infante-Ventura D, de Armas Castellano A, de Pablos-Rodríguez P, Rueda-Domínguez A, Serrano-Aguilar P, Trujillo-Martín MM. Molecular Biomarkers for the Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis. EUR UROL SUPPL 2022; 46:105-127. [PMID: 36388432 PMCID: PMC9664479 DOI: 10.1016/j.euros.2022.10.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/18/2022] [Indexed: 11/11/2022] Open
Abstract
Context Prostate cancer (PCa) is the second most common type of cancer in men. Individualized risk stratification is crucial to adjust decision-making. A variety of molecular biomarkers have been developed in order to identify patients at risk of clinically significant PCa (csPCa) defined by the most common PCa risk stratification systems. Objective The present study aims to examine the effectiveness (diagnostic accuracy) of blood or urine-based PCa biomarkers to identify patients at high risk of csPCa. Evidence acquisition A systematic review of the literature was conducted. Medline and EMBASE were searched from inception to March 2021. Randomized or nonrandomized clinical trials, and cohort and case-control studies were eligible for inclusion. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Pooled estimates of sensitivity, specificity, and area under the curve were obtained. Evidence synthesis Sixty-five studies (N = 34 287) were included. Not all studies included prostate-specific antigen-selected patients. The pooled data showed that the Prostate Health Index (PHI), with any cutoff point between 15 and 30, had sensitivity of 0.95-1.00 and specificity of 0.14-0.33 for csPCa detection. The pooled estimates for SelectMDx test sensitivity and specificity were 0.84 and 0.49, respectively. Conclusions The PHI test has a high diagnostic accuracy rate for csPCa detection, and its incorporation in the diagnostic process could reduce unnecessary biopsies. However, there is a lack of evidence on patient-important outcomes and thus more research is needed. Patient summary It has been possible to verify that the application of biomarkers could help detect prostate cancer (PCa) patients with a higher risk of poorer evolution. The Prostate Health Index shows an ability to identify 95-100 for every 100 patients suffering from clinically significant PCa who take the test, preventing unnecessary biopsies in 14-33% of men without PCa or insignificant PCa.
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Affiliation(s)
- Tasmania del Pino-Sedeño
- Canary Islands Health Research Institute Foundation (FIISC), Tenerife, Spain
- The Spanish Network of Agencies for Health Technology Assessment and Services of the National Health System (RedETS), Madrid, Spain
- European University of the Canary Islands (UEC), Santa Cruz de Tenerife, Spain
- Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Tenerife, Spain
| | - Diego Infante-Ventura
- Canary Islands Health Research Institute Foundation (FIISC), Tenerife, Spain
- The Spanish Network of Agencies for Health Technology Assessment and Services of the National Health System (RedETS), Madrid, Spain
| | - Aythami de Armas Castellano
- Canary Islands Health Research Institute Foundation (FIISC), Tenerife, Spain
- The Spanish Network of Agencies for Health Technology Assessment and Services of the National Health System (RedETS), Madrid, Spain
| | - Pedro de Pablos-Rodríguez
- Department of Urology, Valencian Institute of Oncology Foundation, Valencia, Spain
- Doctoral School of University of Las Palmas de Gran Canaria, Las Palmas, Spain
- Research Institute of Biochemical and Health Sciences, Barcelona, Spain
| | - Antonio Rueda-Domínguez
- Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain
- Research Network on Health Services in Chronic Diseases (REDISSEC), Madrid, Spain
| | - Pedro Serrano-Aguilar
- The Spanish Network of Agencies for Health Technology Assessment and Services of the National Health System (RedETS), Madrid, Spain
- Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Tenerife, Spain
- Research Network on Health Services in Chronic Diseases (REDISSEC), Madrid, Spain
- Institute of Biomedical Technologies (ITB). University of La Laguna, Tenerife, Spain
- Evaluation Unit (SESCS), Canary Islands Health Service (SCS), Tenerife, Spain
| | - María M. Trujillo-Martín
- Canary Islands Health Research Institute Foundation (FIISC), Tenerife, Spain
- The Spanish Network of Agencies for Health Technology Assessment and Services of the National Health System (RedETS), Madrid, Spain
- Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Tenerife, Spain
- Research Network on Health Services in Chronic Diseases (REDISSEC), Madrid, Spain
- Institute of Biomedical Technologies (ITB). University of La Laguna, Tenerife, Spain
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22
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Wang L, He W, Shi G, Zhao G, Cen Z, Xu F, Tian W, Zhao X, Mo C. Accuracy of novel urinary biomarker tests in the diagnosis of prostate cancer: A systematic review and network meta-analysis. Front Oncol 2022; 12:1048876. [PMID: 36457516 PMCID: PMC9706202 DOI: 10.3389/fonc.2022.1048876] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 10/26/2022] [Indexed: 11/16/2022] Open
Abstract
ObjectiveThe purpose of this study was to conduct a network meta-analysis comparing the diagnostic value of different urinary markers for prostate cancer.MethodsAs of June 2022, the literature was retrieved by searching Pubmed, EMBASE, Web of Science databases and other databases. The methodological quality of included studies was assessed using the Cochrane Collaboration’s risk of bias tool, and publication bias was assessed using funnel plots. The surface under the cumulative ranking curve (SUCRA) values was used to determine the most effective diagnostic method and the data were analyzed accordingly using data analysis software.ResultsA total of 16 articles was included including 9952 patients. The ranking results of network meta-analysis showed that the diagnostic performance of the four urine markers Selectmdx, MIPS, PCA3 and EPI was better than that of PSA. Among them, the specificity, positive predictive value and diagnostic accuracy of Selectmdx ranked first in the SUCRA ranking (SUCRA values: 85.2%, 88.3%, 97.1%), and the sensitivity ranked second in the SUCRA ranking (SUCRA value: 54.4%), and the negative predictive value ranked fourth in SUCRA (SUCRA value: 51.6%). The most sensitive screening tool was MIPS (SUCRA value: 67.1%), and it was also the second screening tool ranked higher in specificity, positive predictive value, negative predictive value and diagnostic accuracy (SUCRA value: 56.5%, respectively)., 57.1%, 67.9%, 74.3%). The high negative predictive value SUCRA ranking is EPI (SUCRA value: 68.0%), its sensitivity ranks third (SUCRA value: 45.6%), and its specificity, positive predictive value and diagnostic accuracy are ranked fourth (SUCRA values are: 45%, 38.2%, 35.8%).ConclusionAccording to the network ranking diagram, we finally concluded that Selectmdx and MIPS can be used as the most suitable urine markers for prostate cancer screening and diagnosis. To further explore the diagnostic value of different urinary markers in the screening of PCa patients.Systematic Review Registrationhttps://inplasy.com/, identifier INPLASY202290094.
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Affiliation(s)
- Leibo Wang
- Surgery, Guizhou Orthopaedic Hospital, Guiyang, Guizhou, China
- *Correspondence: Leibo Wang, ; Guanyu Shi,
| | - Wei He
- Surgery, Guizhou Orthopaedic Hospital, Guiyang, Guizhou, China
| | - Guanyu Shi
- Department of Urology, Fenggang County People’s Hospital, Zunyi, Guizhou, China
- *Correspondence: Leibo Wang, ; Guanyu Shi,
| | - Guoqiang Zhao
- Surgery, Guizhou Orthopaedic Hospital, Guiyang, Guizhou, China
| | - Zhuangding Cen
- Surgery, Guizhou Orthopaedic Hospital, Guiyang, Guizhou, China
| | - Feng Xu
- Surgery, Guizhou Orthopaedic Hospital, Guiyang, Guizhou, China
| | - Wu Tian
- Surgery, Guizhou Orthopaedic Hospital, Guiyang, Guizhou, China
| | - Xin Zhao
- Surgery, Guizhou Orthopaedic Hospital, Guiyang, Guizhou, China
| | - Chishou Mo
- Surgery, Guizhou Orthopaedic Hospital, Guiyang, Guizhou, China
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23
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Fan A, Zhang Y, Cheng J, Li Y, Chen W. A novel prognostic model for prostate cancer based on androgen biosynthetic and catabolic pathways. Front Oncol 2022; 12:950094. [PMID: 36439479 PMCID: PMC9685527 DOI: 10.3389/fonc.2022.950094] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 10/20/2022] [Indexed: 08/14/2023] Open
Abstract
Prostate cancer (PCa) is one of the most common malignancies in males globally, and its pathogenesis is significantly related to androgen. As one of the important treatments for prostate cancer, androgen deprivation therapy (ADT) inhibits tumor proliferation by controlling androgen levels, either surgically or pharmacologically. However, patients treated with ADT inevitably develop biochemical recurrence and advance to castration-resistant prostate cancer which has been reported to be associated with androgen biosynthetic and catabolic pathways. Thus, gene expression profiles and clinical information of PCa patients were collected from TCGA, MSKCC, and GEO databases for consensus clustering based on androgen biosynthetic and catabolic pathways. Subsequently, a novel prognostic model containing 13 genes (AFF3, B4GALNT4, CD38, CHRNA2, CST2, ADGRF5, KLK14, LRRC31, MT1F, MT1G, SFTPA2, SLC7A4, TDRD1) was constructed by univariate cox regression, lasso regression, and multivariate cox regression. Patients were divided into two groups based on their risk scores: high risk (HS) and low risk (LS), and survival analysis was used to determine the difference in biochemical recurrence-free time between the two. The results were validated on the MSKCC dataset and the GEO dataset. Functional enrichment analysis revealed some pivotal pathways that may have an impact on the prognosis of patients including the CDK-RB-E2F axis, G2M checkpoint, and KRAS signaling. In addition, somatic mutation, immune infiltration, and drug sensitivity analyses were performed to further explore the characteristics of HS and LS groups. Besides, two potential therapeutic targets, BIRC5 and RHOC, were identified by us in prostate cancer. These results indicate that the prognostic model may serve as a predictive tool to guide clinical treatment and provide new insight into the basic research in prostate cancer.
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Affiliation(s)
| | | | | | | | - Wei Chen
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
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24
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Combes AD, Palma CA, Calopedos R, Wen L, Woo H, Fulham M, Leslie S. PSMA PET-CT in the Diagnosis and Staging of Prostate Cancer. Diagnostics (Basel) 2022; 12:2594. [PMID: 36359439 PMCID: PMC9689635 DOI: 10.3390/diagnostics12112594] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 10/13/2022] [Accepted: 10/24/2022] [Indexed: 08/07/2023] Open
Abstract
Prostate cancer is the most common cancer and the second leading cause of cancer death in men. The imaging assessment and treatment of prostate cancer has vastly improved over the past decade. The introduction of PSMA PET-CT has improved the detection of loco-regional and metastatic disease. PSMA PET-CT also has a role in the primary diagnosis and staging, in detecting biochemical recurrence after curative treatment and in metastasis-directed therapy. In this paper we review the role of PSMA PET-CT in prostate cancer.
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Affiliation(s)
- Alexander D. Combes
- Department of Urology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia
| | - Catalina A. Palma
- Department of Urology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia
| | - Ross Calopedos
- Department of Urology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia
| | - Lingfeng Wen
- Department of Molecular Imaging, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia
- Faculty of Engineering and Computer Science, University of Sydney, Sydney, NSW 2006, Australia
| | - Henry Woo
- Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia
- Department of Urology, Chris O’Brien Lifehouse, Sydney, NSW 2050, Australia
| | - Michael Fulham
- Department of Molecular Imaging, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia
- Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia
| | - Scott Leslie
- Department of Urology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia
- Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia
- Department of Urology, Chris O’Brien Lifehouse, Sydney, NSW 2050, Australia
- RPA Institute of Academic Surgery, Sydney, NSW 2050, Australia
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25
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Xiao J, Li Y, Liu Y, Chen Y, He Z, Peng S, Yin Y. The involvement of homeobox-C 4 in predicting prognosis and unraveling immune landscape across multiple cancers via integrated analysis. Front Genet 2022; 13:1021473. [DOI: 10.3389/fgene.2022.1021473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 09/22/2022] [Indexed: 11/13/2022] Open
Abstract
Background: There has been growing evidence that the aberrantly expressed Homeobox-C 4 (HOXC4) plays crucial roles in the development of some cancer types. However, it remains unclear as far as its expression patterns and prognostic significance are concerned, as is tumor immunity.Methods: To investigate the expression levels and prognostic implications of HOXC4, multiple data sources were used in conjunction with quantitative real-time polymerase chain reaction (qRT-PCR) verification. Afterward, diverse immunological-related analyses, along with anti-cancer drug sensitivity, were performed in a number of cancer types. A further exploration of the underlying mechanisms of HOXC4 in tumorigenesis and immunity was carried out using the Gene Set Enrichment Analysis (GSEA) and the Gene Set Variation Analysis (GSVA).Results: Based on extensive database mining, HOXC4 was ubiquitously expressed across 21 tumor cell lines and significantly higher than that of normal tissues in 21 tumor types. The outcome of survival analysis including overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS) and progression-free interval (PFI) revealed that upregulation of HOXC4 expression in several cancers was associated with worse prognosis. Additionally, HOXC4 was observed to correlate closely with colon adenocarcinoma (COAD), head and neck squamous cell carcinoma (HNSC), lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), rectum adenocarcinoma (READ), and thyroid carcinoma (THCA) in terms of tumor immune cells infiltration. As a result of our comprehensive pan-cancer study, we have identified a significant link between the expression of HOXC4 and the efficacy of immunotherapy-related treatments, together with anti-cancer drug sensitivity. As a final note, HOXC4 was found to modulate multiple signaling pathways involved in tumorigenesis and immunity.Conclusion: HOXC4 has been implicated in our study for the first time as an oncogene in cancers with a poor prognosis, potentially laying the groundwork for promising clinical biomarkers and immunotherapy approaches.
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26
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Combination of PI-RADS score and mRNA urine test—A novel scoring system for improved detection of prostate cancer. PLoS One 2022; 17:e0271981. [PMID: 35960727 PMCID: PMC9374213 DOI: 10.1371/journal.pone.0271981] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 07/11/2022] [Indexed: 12/24/2022] Open
Abstract
Available tests to detect clinically significant prostate cancer frequently lead to overdiagnosis and overtreatment. Our study assessed the feasibility of combining a urinary biomarker-based risk score (SelectMDx®) and multiparametric MRI outcomes in order to identify patients with prostate cancer on prostate biopsy with increased accuracy and reliability. Samples of 74 men with suspicion of prostate cancer and available multiparametric MRI were analysed in a prospective cross-sectional study design. First-voided urine for determination of HOXC6 and DLX1 mRNA levels was collected after digital rectal examination and prior to MRI/ultrasound fusion-guided prostate biopsy. All multiparametric MRI images were centrally reviewed by two experienced radiologists blinded for urine test results and biopsy outcome. The PI-RADS v2 was used. SelectMDx® score, PI-RADS and Gleason Sore were obtained. Associations between Gleason Score, PI-RADS scores and SelectMDx® were assessed using ANOVA and t-test. Sensitivity and specificity were assessed and evaluated as area-under-the-curve of the receiver operating characteristic. Upon biopsy, 59.5% of patients were diagnosed with prostate cancer, whereby 40.6% had high-grade prostate cancer (GS ≥ 7a). SelectMDx® scores were significantly higher for patients with positive biopsy findings (49.07 ± 25.99% vs. 22.00 ± 26.43%; p < 0.001). SelectMDx® scores increased with higher PI-RADS scores. Combining SelectMDx®, history of prior biopsy with benign histology and PI-RADS scores into a novel scoring system led to significant prostate cancer detection rates with tiered detection rate of 39%, 58%, 81% and 100% for Gleason grade group II, III, IV, and V, respectively. The area-under-the-curve for our novel sum score in receiver operating characteristic analysis was 0.84. The synergistic combination of two non-invasive tests into a sum score with increased sensitivity may help avoiding unnecessary biopsies for initial prostate cancer diagnosis. For confirmation, further prospective studies with larger sample sizes and univariate and multivariate regression analyses and decision curve analyses are required.
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Velmurugan P, Mohanavel V, Shrestha A, Sivakumar S, Oyouni AAA, Al-Amer OM, Alzahrani OR, Alasseiri MI, Hamadi A, Alalawy AI. Developing a Multimodal Model for Detecting Higher-Grade Prostate Cancer Using Biomarkers and Risk Factors. BIOMED RESEARCH INTERNATIONAL 2022; 2022:9223400. [PMID: 35722463 PMCID: PMC9205705 DOI: 10.1155/2022/9223400] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/02/2022] [Accepted: 05/13/2022] [Indexed: 11/25/2022]
Abstract
A technique to predict crucial clinical prostate cancer (PC) is desperately required to prevent diagnostic errors and overdiagnosis. To create a multimodal model that incorporates long-established messenger RNA (mRNA) indicators and conventional risk variables for identifying individuals with severe PC on prostatic biopsies. Urinary has gathered for mRNA analysis following a DRE and before a prostatic examination in two prospective multimodal investigations. A first group (n = 489) generated the multimodal risk score, which was then medically verified in a second group (n = 283). The reverse transcription qualitative polymerase chain reaction determined the mRNA phase. Logistic regression was applied to predict risk in patients and incorporate health risks. The area under the curve (AUC) was used to compare models, and clinical efficacy was assessed by using a DCA. The amounts of sixth homeobox clustering and first distal-less homeobox mRNA have been strongly predictive of high-grade PC detection. In the control subjects, the multimodal method achieved a total AUC of 0.90, with the most important aspects being the messenger riboneuclic acid features' PSA densities and previous cancer-negative tests as a nonsignificant design ability to contribute to PSA, aging, and background. An AUC of 0.86 was observed for one more model that added DRE as an extra risk component. Two methods were satisfactorily verified without any significant changes within the area under the curve in the validation group. DCA showed a massive net advantage and the highest decrease in inappropriate costs.
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Affiliation(s)
- Palanivel Velmurugan
- Centre for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, Selaiyur, Chennai, Tamil Nadu, India
| | - Vinayagam Mohanavel
- Centre for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, Chennai 600073, Tamil Nadu, India
- Department of Mechanical Engineering, Chandigarh University, Mohali 140413, Punjab, India
| | - Anupama Shrestha
- Department of Plant Protection, Himalayan College of Agricultural Sciences and Technology, Kalanki, Kathmandu, Nepal PO box 44600
- Research Institute of Agriculture and Applied Science, Tokha Kathmandu, Nepal 2356
| | - Subpiramaniyam Sivakumar
- Department of Bioenvironmental Energy, College of Natural Resources and Life Science, Pusan National University, Miryang-Si, Gyeongsangnam-do 50463, Republic of Korea
| | - Atif Abdulwahab A. Oyouni
- Department of Biology, Faculty of Sciences, University of Tabuk, Tabuk, Saudi Arabia
- Genome and Biotechnology Unit, Faculty of Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Osama M. Al-Amer
- Genome and Biotechnology Unit, Faculty of Sciences, University of Tabuk, Tabuk, Saudi Arabia
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Othman R. Alzahrani
- Department of Biology, Faculty of Sciences, University of Tabuk, Tabuk, Saudi Arabia
- Genome and Biotechnology Unit, Faculty of Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Mohammed I. Alasseiri
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Abdullah Hamadi
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Adel Ibrahim Alalawy
- Genome and Biotechnology Unit, Faculty of Sciences, University of Tabuk, Tabuk, Saudi Arabia
- Department of Biochemistry, Faculty of Sciences, University of Tabuk, Tabuk, Saudi Arabia
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Bioinformatic investigation and functional analysis of 214 hereditary genes identified non-coding RNAs as therapeautic tool for breast cancer management. GENE REPORTS 2022. [DOI: 10.1016/j.genrep.2022.101565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Liu Y, Qiu S, Sun D, Xiong T, Xiang Q, Li Q. Construction of a Comprehensive Diagnostic Scoring Model for Prostate Cancer Based on a Novel Six-Gene Panel. Front Genet 2022; 13:831162. [PMID: 35559023 PMCID: PMC9086319 DOI: 10.3389/fgene.2022.831162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 03/14/2022] [Indexed: 12/24/2022] Open
Abstract
Accumulating evidence indicates that the N6-methyladenosine (m6A) modification plays a critical role in human cancers. Given the current understanding of m6A modification, this process is believed to be dynamically regulated by m6A regulators. Although the discovery of m6A regulators has greatly enhanced our understanding of the mechanism underlying m6A modification in cancers, the function and role of m6A in the context of prostate cancer (PCa) remain unclear. Here, we aimed to establish a comprehensive diagnostic scoring model that can act as a complement to prostate-specific antigen (PSA) screening. To achieve this, we first drew the landscape of m6A regulators and constructed a LASSO-Cox model using three risk genes (METTL14, HNRNP2AB1, and YTHDF2). Particularly, METTL14 expression was found to be significantly related to overall survival, tumor T stage, relapse rate, and tumor microenvironment of PCa patients, showing that it has important prognostic value. Furthermore, for the sake of improving the predictive ability, we presented a comprehensive diagnostic scoring model based on a novel 6-gene panel by combining with genes found in our previous study, and its application potential was further validated by the whole TCGA and ICGC cohorts. Our study provides additional clues and insights regarding the treatment and diagnosis of PCa patients.
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Affiliation(s)
- Yunfeng Liu
- School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China
- Guangdong Provincial Engineering and Technology Research Center of Biopharmaceuticals, South China University of Technology, Guangzhou, China
| | - Simei Qiu
- School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China
| | - Dongshan Sun
- School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China
| | - Ting Xiong
- School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China
| | - Qiuling Xiang
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Quhuan Li
- School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China
- Guangdong Provincial Engineering and Technology Research Center of Biopharmaceuticals, South China University of Technology, Guangzhou, China
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Sari Motlagh R, Yanagisawa T, Kawada T, Laukhtina E, Rajwa P, Aydh A, König F, Pallauf M, Huebner NA, Baltzer PA, Karakiewicz PI, Heidenreich A, Shariat SF. Accuracy of SelectMDx compared to mpMRI in the diagnosis of prostate cancer: a systematic review and diagnostic meta-analysis. Prostate Cancer Prostatic Dis 2022; 25:187-198. [PMID: 35414118 DOI: 10.1038/s41391-022-00538-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/15/2022] [Accepted: 03/30/2022] [Indexed: 12/18/2022]
Abstract
BACKGROUND The SelectMDx test is a promising biomarker that is developed based on detecting urinary messenger RNA in combination with clinical prostate cancer (PCa) risk factors. We aimed to compare SelectMDx and mpMRI as a diagnostic test in detecting PCa and high grade(HG)-PCa in men suspected to have PCa. METHODS According to PRISMA, a systematic search was performed using major web databases for studies published before September 30, 2021. Studies that compared sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of SelectMDx and/or mpMRI were included. The bivariate random model that plotted sensitivity, specificity, PPV, NPV, and likelihood ratio (LR) for PCa and HG-PCa detection was applied to compare SelectMDx, mpMRI, and combination strategies (both positive and one or both positive). RESULTS Seven studies comprising 1328 patients who had undergone SelectMDx and mpMRI to detect PCa were included. Regarding PCa detection, SelectMDx had a pooled sensitivity of 81%, specificity of 69.8%, PPV of 64.7%, NPV of 85%, and LRs of +2.68 to -0.27, while mpMRI had a pooled sensitivity of 80.8%, specificity of 73.4%, PPV of 72.4%, NPV of 83.5%, and LRs of +3.03 to -0.26. The one or both positive strategy had the highest sensitivity (96.3%), NPV (95.7%), and the lowest -LR (0.06). While the both positive strategy had the highest specificity (80.9%), the PPV (76.5%) and +LR (3.68). In the scenario of PI-RADS 3 lesions not being biopsied in case of a negative SelectMDx (n = 44), unnecessary biopsies would be reduced by 42% (44/105) while the risk of missing HG-PCa would be 9% (4/44). CONCLUSION The performance of SelectMDx is comparable to that of mpMRI with regards to PCa and HG-PCa detection. In addition, this biomarker could help refine the clinical decision-making regarding the necessity of a biopsy in patients suspected to has been PCa.
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Affiliation(s)
- Reza Sari Motlagh
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Takafumi Yanagisawa
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Tatsushi Kawada
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Ekaterina Laukhtina
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia
| | - Pawel Rajwa
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Urology, Medical University of Silesia, Zabrze, Poland
| | - Abdulmajeed Aydh
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Urology, King Faisal Medical City, Abha, Saudi Arabia
| | - Frederik König
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Maximilan Pallauf
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Urology, University Hospital Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria
| | - Nicolai A Huebner
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Working Group for Diagnostic imaging in Urology (ABDU), Austrian association of Urology (ÖGU), Vienna, Austria
| | - Pascal A Baltzer
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Pierre I Karakiewicz
- Cancer Prognostics and Health outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada
| | - Axel Heidenreich
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Urology, University Hospital Cologne, Cologne, Germany
| | - Shahrokh F Shariat
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. .,Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. .,Department of Urology, Weill Cornell Medical College, New York, NY, USA. .,Department of Urology, University of Texas Southwestern, Dallas, TX, USA. .,Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. .,Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. .,Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan.
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Expression Profiles of HOXC6 Predict the Survival of Glioblastoma Patients and Correlate with Cell Cycle. JOURNAL OF ONCOLOGY 2022; 2022:8656865. [PMID: 35432534 PMCID: PMC9007636 DOI: 10.1155/2022/8656865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 12/14/2021] [Accepted: 03/13/2022] [Indexed: 12/05/2022]
Abstract
The goal of this study was to investigate the homeobox (HOX) gene expression status and its prognostic value in glioblastoma multiforme (GBM) and to uncover the biological processes related to its expression. The prognostic value of HOX genes in GBM was systematically investigated by a genome-wide analysis of HOX gene expression profiles in GBM patient samples in The Cancer Genome Atlas (TCGA) project (microarray dataset) and validation datasets. Using the differentially expressed gene (DEG) analysis and a Cox regression model, we discovered that the HOXC6 could stratify patients into significantly different survival (p = 0.0012, log-rank test) groups in the training cohort. TCGA RNA-seq and GSE16011 datasets were used for validation. Multivariate Cox and stratification analysis indicated that HOXC6 was an independent prognostic factor after adjusting for other clinical covariates. Bioinformatic analysis suggested that the HOXC6 might be involved in the cell cycle-related biological processes and pathways that are well established in the context of glioblastoma tumorigenesis. We further explored the bioinformatic implications by gene set enrichment analysis (GSEA). Tumor cell biology experiments verified the role of HOXC6 in proliferation and cell cycle progression. In conclusion, HOXC6 might be a candidate biomarker gene for individual treatment optimization of glioblastoma. HOXC6 expression has a significant prognostic value and is related to the cell cycle process in glioblastoma.
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32
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Lin Y, Liu G, Liu C, Xie H, Wang X, Huang Y, Jin L, Chen H. Urothelial carcinoembryonic antigen 1 score for early detection of prostate cancer and risk prediction. Cancer Med 2022; 11:2875-2885. [PMID: 35289508 PMCID: PMC9359874 DOI: 10.1002/cam4.4629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 01/24/2022] [Accepted: 02/21/2022] [Indexed: 11/09/2022] Open
Abstract
UCA1 score appears useful in detecting nonhigh-risk (including very low-, low-, or intermediate-risk) prostate cancer. Combination of the PSA level and the UCA1 score may significantly reduce the burden of prostate biopsy.
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Affiliation(s)
- Youdong Lin
- Department of Clinical Laboratory Medicine, Fujian Provincial Hospital, Fujian Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
| | - Guihua Liu
- Department of Children Health Care, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
| | - Chun Liu
- Department of urinary surgery, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Hui Xie
- Department of urinary surgery, Fuzhou NO. 1 Hospital Affiliated with Fujian Medical University, Fuzhou, Fujian, China
| | - Xiaoxian Wang
- Department of Clinical Laboratory Medicine, Fuzhou NO. 1 Hospital Affiliated with Fujian Medical University, Fuzhou, Fujian, China
| | - Yudian Huang
- Department of Pathology, Fuzhou NO. 1 Hospital Affiliated with Fujian Medical University, Fuzhou, Fujian, China
| | - Long Jin
- Department of Pathology, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Huidan Chen
- Department of Clinical Laboratory Medicine, Fujian Provincial Hospital, Fujian Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
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Henning GM, Andriole GL, Kim EH. Liquid biomarkers for early detection of prostate cancer and summary of available data for their use in African-American men. Prostate Cancer Prostatic Dis 2022; 25:180-186. [PMID: 35246608 DOI: 10.1038/s41391-022-00507-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 12/20/2021] [Accepted: 01/27/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND Several liquid biomarker tests have been developed to account for the limitations of prostate specific antigen (PSA) screening prior to prostate biopsy. African ancestry is an established risk factor for prostate cancer (PCa) and must be particularly considered when evaluating patients with liquid biomarkers. While multiple tests have been developed over decades of exploration, recent advances can help patients and physicians incorporate data into a broader clinical context. METHODS We sought to review currently available liquid biomarker tests in a practical, clinically directed fashion with particular focus on performance in men with African ancestry. We reviewed discovery and validation studies and highlight important considerations for each test. RESULTS We discuss the advantages and limitations of percent free PSA, Prostate Health Index, Progensa® PCA3, ExoDx® Prostate Test, SelectMDx®, 4Kscore® Test, and Mi-Prostate Score and summarize salient studies on their use. A literature review of evidence specifically for men with African ancestry was conducted and available studies were summarized. CONCLUSIONS Liquid biomarkers can be useful tools for aiding in risk stratification prior to prostate biopsy. Use of such tests should be individualized based on a thorough knowledge of supporting evidence and the goals of the patient and physician. Further study should prioritize evaluation of such biomarkers in men with African ancestry.
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Affiliation(s)
- Grant M Henning
- Washington University School of Medicine, St. Louis, MO, USA.
| | | | - Eric H Kim
- Washington University School of Medicine, St. Louis, MO, USA
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Marsden T, McCartan N, Brown L, Rodriguez-Justo M, Syer T, Brembilla G, Van Hemelrijck M, Coolen T, Attard G, Punwani S, Moore CM, Ahmed HU, Emberton M, on behalf of the ReIMAGINE Study Group. The ReIMAGINE prostate cancer risk study protocol: A prospective cohort study in men with a suspicion of prostate cancer who are referred onto an MRI-based diagnostic pathway with donation of tissue, blood and urine for biomarker analyses. PLoS One 2022; 17:e0259672. [PMID: 35202397 PMCID: PMC8870538 DOI: 10.1371/journal.pone.0259672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 10/24/2021] [Indexed: 11/18/2022] Open
Abstract
INTRODUCTION The ReIMAGINE Consortium was conceived to develop risk-stratification models that might incorporate the full range of novel prostate cancer (PCa) diagnostics (both commercial and academic). METHODS ReIMAGINE Risk is an ethics approved (19/LO/1128) multicentre, prospective, observational cohort study which will recruit 1000 treatment-naive men undergoing a multi-parametric MRI (mpMRI) due to an elevated PSA (≤20ng/ml) or abnormal prostate examination who subsequently had a suspicious mpMRI (score≥3, stage ≤T3bN0M0). Primary outcomes include the detection of ≥Gleason 7 PCa at baseline and time to clinical progression, metastasis and death. Baseline blood, urine, and biopsy cores for fresh prostate tissue samples (2 targeted and 1 non-targeted) will be biobanked for future analysis. High-resolution scanning of pathology whole-slide imaging and MRI-DICOM images will be collected. Consortium partners will be granted access to data and biobanks to develop and validate biomarkers using correlation to mpMRI, biopsy-based disease status and long-term clinical outcomes. RESULTS Recruitment began in September 2019(n = 533). A first site opened in September 2019 (n = 296), a second in November 2019 (n = 210) and a third in December 2020 (n = 27). Acceptance to the study has been 65% and a mean of 36.5ml(SD+/-10.0), 12.9ml(SD+/-3.7) and 2.8ml(SD+/-0.7) urine, plasma and serum donated for research, respectively. There are currently 4 academic and 15 commercial partners spanning imaging (~9 radiomics, artificial intelligence/machine learning), fluidic (~3 blood-based and ~2urine-based) and tissue-based (~1) biomarkers. CONCLUSION The consortium will develop, or adjust, risk models for PCa, and provide a platform for evaluating the role of novel diagnostics in the era of pre-biopsy MRI and targeted biopsy.
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Affiliation(s)
- Teresa Marsden
- UCL Division of Surgical & Interventional Sciences, University College London, London, United Kingdom
- Department of Urology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
- * E-mail:
| | - Neil McCartan
- UCL Division of Surgical & Interventional Sciences, University College London, London, United Kingdom
| | - Louise Brown
- MRC Clinical Trials Unit, University College London, London, United Kingdom
| | - Manuel Rodriguez-Justo
- Research Department of Pathology, University College London, London, United Kingdom
- Department of Pathology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
| | - Tom Syer
- Centre for Medical Imaging, University College London, London, United Kingdom
| | - Giorgio Brembilla
- Centre for Medical Imaging, University College London, London, United Kingdom
| | - Mieke Van Hemelrijck
- School of Cancer and Pharmaceutical Sciences, Kings College London, London, United Kingdom
| | - Ton Coolen
- London Institute for Mathematical Sciences, London, United Kingdom
| | - Gerhardt Attard
- Cancer Institute, University College London, London, United Kingdom
| | - Shonit Punwani
- Centre for Medical Imaging, University College London, London, United Kingdom
| | - Caroline M. Moore
- UCL Division of Surgical & Interventional Sciences, University College London, London, United Kingdom
- Department of Urology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
| | - Hashim U. Ahmed
- Imperial Prostate, Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
- Imperial Urology, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Mark Emberton
- UCL Division of Surgical & Interventional Sciences, University College London, London, United Kingdom
- Department of Urology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
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Falagario UG, Sanguedolce F, Dovey Z, Carbonara U, Crocerossa F, Papastefanou G, Autorino R, Recchia M, Ninivaggi A, Busetto GM, Annese P, Carrieri G, Cormio L. Prostate cancer biomarkers: a practical review based on different clinical scenarios. Crit Rev Clin Lab Sci 2022; 59:297-308. [PMID: 35200064 DOI: 10.1080/10408363.2022.2033161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Traditionally, diagnosis and staging of prostate cancer (PCa) have been based on prostate-specific antigen (PSA) level, digital rectal examination (DRE), and transrectal ultrasound (TRUS) guided prostate biopsy. Biomarkers have been introduced into clinical practice to reduce the overdiagnosis and overtreatment of low-grade PCa and increase the success of personalized therapies for high-grade and high-stage PCa. The purpose of this review was to describe available PCa biomarkers and examine their use in clinical practice. A nonsystematic literature review was performed using PubMed and Scopus to retrieve papers related to PCa biomarkers. In addition, we manually searched websites of major urological associations for PCa guidelines to evaluate available evidence and recommendations on the role of biomarkers and their potential contribution to PCa decision-making. In addition to PSA and its derivates, thirteen blood, urine, and tissue biomarkers are mentioned in various PCa guidelines. Retrospective studies have shown their utility in three main clinical scenarios: (1) deciding whether to perform a biopsy, (2) distinguishing patients who require active treatment from those who can benefit from active surveillance, and (3) defining a subset of high-risk PCa patients who can benefit from additional therapies after RP. Several validated PCa biomarkers have become commercially available in recent years. Guidelines now recommend offering these tests in situations in which the assay result, when considered in combination with routine clinical factors, is likely to affect management. However, the lack of direct comparisons and the unproven benefits, in terms of long-term survival and cost-effectiveness, prevent these biomarkers from being integrated into routine clinical use.
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Affiliation(s)
- Ugo Giovanni Falagario
- Department of Urology and Organ Transplantation, University of Foggia, Foggia, Italy.,Division of Urology, VCU Health System, Richmond, VA, USA.,Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Zach Dovey
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | | | - George Papastefanou
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Marco Recchia
- Department of Urology and Organ Transplantation, University of Foggia, Foggia, Italy
| | - Antonella Ninivaggi
- Department of Urology and Organ Transplantation, University of Foggia, Foggia, Italy
| | - Gian Maria Busetto
- Department of Urology and Organ Transplantation, University of Foggia, Foggia, Italy
| | - Pasquale Annese
- Department of Urology and Organ Transplantation, University of Foggia, Foggia, Italy
| | - Giuseppe Carrieri
- Department of Urology and Organ Transplantation, University of Foggia, Foggia, Italy
| | - Luigi Cormio
- Department of Urology and Organ Transplantation, University of Foggia, Foggia, Italy
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Zhang D, Yin H, Bauer TL, Rogers MP, Velotta JB, Morgan CT, Du W, Xu P, Qian X. Development of a novel miR-3648-related gene signature as a prognostic biomarker in esophageal adenocarcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2022; 9:1702. [PMID: 34988211 PMCID: PMC8667142 DOI: 10.21037/atm-21-6237] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 11/29/2021] [Indexed: 11/06/2022]
Abstract
Background Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature. Methods The gene expression data of 87 EA tumor samples and 67 normal tissue samples from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database were downloaded, respectively. Weighted gene co-expression network analysis (WGCNA), the CIBERSORT algorithm, and Cox regression analysis were applied to identify IRGs and to construct a prognostic signature and nomogram. Results MiR-3648 was expectedly highly expressed in EA tumor tissues (P=2.6e-8), and related to the infiltration of activated natural killer cells (NK cells) and activated CD4 T lymphocytes (CD4 cells). A total of 70 miR-3648-targeted genes related to immune cell infiltration were identified. Among them, 4 genes (C10orf55, DLL4, PANX2, and NKAIN1) were closely related to overall survival (OS), and were thus selected to construct a 4-gene risk score (RS). The RS had a superior capability to predict OS [area under the curve (AUC) =0.740 for 1 year; AUC =0.717 for 3 years; AUC =0.622 for 5 years]. A higher score was indicative of a poorer prognosis than a lower score [hazard ratio (HR) =2.71; 95% confidence interval (CI): 1.45-5.09; P=0.002]. Furthermore, the nomogram formed by combining the RS and the TNM classification of malignant tumors (TNM stage) improved the accuracy of survival prediction [Harrell's concordance index (C-index) =0.698]. Conclusions MiR-3648 may play a critical role in EA pathogenesis. The novel 4-gene signature may serve as a prognostic tool to manage patients with EA.
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Affiliation(s)
- Donglei Zhang
- Department of Thoracic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hang Yin
- Department of Thoracic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Thomas L Bauer
- Department of General Surgery, Jersey Shore University Medical Center, Neptune, NJ, USA
| | - Michael P Rogers
- Department of Surgery, University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | - Jeffrey B Velotta
- Department of Thoracic Surgery, Oakland Medical Center, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Clinton T Morgan
- Division of Cardiothoracic Surgery, Department of Surgery, University of Kentucky, Lexington, KY, USA
| | - Weijia Du
- Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ping Xu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xiaozhe Qian
- Department of Thoracic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Mugoni V, Ciani Y, Nardella C, Demichelis F. Circulating RNAs in prostate cancer patients. Cancer Lett 2022; 524:57-69. [PMID: 34656688 DOI: 10.1016/j.canlet.2021.10.011] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 10/06/2021] [Accepted: 10/09/2021] [Indexed: 12/12/2022]
Abstract
Growing bodies of evidence have demonstrated that the identification of prostate cancer (PCa) biomarkers in the patients' blood and urine may remarkably improve PCa diagnosis and progression monitoring. Among diverse cancer-derived circulating materials, extracellular RNA molecules (exRNAs) represent a compelling component to investigate cancer-related alterations. Once outside the intracellular environment, exRNAs circulate in biofluids either in association with protein complexes or encapsulated inside extracellular vesicles (EVs). Notably, EV-associated RNAs (EV-RNAs) were used for the development of several assays (such as the FDA-approved Progensa Prostate Cancer Antigen 3 (PCA3 test) aiming at improving early PCa detection. EV-RNAs encompass a mixture of species, including small non-coding RNAs (e.g. miRNA and circRNA), lncRNAs and mRNAs. Several methods have been proposed to isolate EVs and relevant RNAs, and to perform RNA-Seq studies to identify potential cancer biomarkers. However, EVs in the circulation of a cancer patient include a multitude of diverse populations that are released by both cancer and normal cells from different tissues, thereby leading to a heterogeneous EV-RNA-associated transcriptional signal. Decrypting the complexity of such a composite signal is nowadays the major challenge faced in the identification of specific tumor-associated RNAs. Multiple deconvolution algorithms have been proposed so far to infer the enrichment of cancer-specific signals from gene expression data. However, novel strategies for EVs sorting and sequencing of RNA associated to single EVs populations will remarkably facilitate the identification of cancer-related molecules. Altogether, the studies summarized here demonstrate the high potential of using EV-RNA biomarkers in PCa and highlight the urgent need of improving technologies and computational approaches to characterize specific EVs populations and their relevant RNA cargo.
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Affiliation(s)
- Vera Mugoni
- Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy
| | - Yari Ciani
- Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy
| | - Caterina Nardella
- Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy
| | - Francesca Demichelis
- Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy.
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Carlsson SV, Murata K, Danila DC, Lilja H. PSA: role in screening and monitoring patients with prostate cancer. Cancer Biomark 2022. [DOI: 10.1016/b978-0-12-824302-2.00001-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Yoneyama T, Yamamoto H, Sutoh Yoneyama M, Tobisawa Y, Hatakeyama S, Narita T, Kodama H, Momota M, Ito H, Narita S, Tsushima F, Mitsuzuka K, Yoneyama T, Hashimoto Y, Duivenvoorden W, Pinthus JH, Kakeda S, Ito A, Tsuchiya N, Habuchi T, Ohyama C. Characteristics of α2,3-sialyl N-glycosylated PSA as a biomarker for clinically significant prostate cancer in men with elevated PSA level. Prostate 2021; 81:1411-1427. [PMID: 34549452 PMCID: PMC9293073 DOI: 10.1002/pros.24239] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 09/10/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND The presence of glycosylated isoforms of prostate-specific antigen (PSA) in prostate cancer (PC) cells is a potential marker of their aggressiveness. We characterized the origin of α2,3-sialylated prostate-specific antigen (S23PSA) by tissue-based sialylation-related gene expression and studied the performance of S23PSA density (S23PSAD) alone and in combination with multiparametric magnetic resonance imaging (MRI) for the detection of clinically significant prostate cancer in men with elevated PSA. METHODS Tissue-based quantification of S23PSA and sialyltransferase and sialidase gene expression was evaluated in 71 radical prostatectomy specimens. The diagnostic performance of S23PSAD was studied in 1099 men retrospectively enrolled in a multicenter systematic biopsy (SBx) cohort. We correlated the S23PSAD with Prostate Imaging Reporting and Data System (PI-RADS) scores in 98 men prospectively enrolled in a single-center MRI-targeted biopsy (MRI-TBx) cohort. The primary outcome was the PC-diagnostic performance of the S23PSAD, the secondary outcome was the avoidable biopsy rate of S23PSAD combined with DRE and total PSA (tPSA), and with or without PI-RADS. RESULTS S23PSA was significantly higher in Gleason pattern 4 and 5 compared with benign prostate tissue. In the retrospective cohort, the performance of S23PSAD for detecting PC was superior to tPSA or PSA density (PSAD) (AUC: 0.7758 vs. 0.6360 and 0.7509, respectively). In the prospective cohort, S23PSAD was superior to tPSA, PSAD, and PI-RADS (AUC: 0.7725 vs. 0.5901, 0.7439 and 0.7305, respectively), and S23PSAD + PI-RADS + DRE + tPSA was superior to DRE + tPSA+PI-RADS with avoidance rate of MRI-TBx (13% vs. 1%) at 30% risk threshold. CONCLUSIONS The diagnostic performance of S23PSAD was superior to conventional strategies but comparable to mpMRI.
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Affiliation(s)
- Tohru Yoneyama
- Department of Glycotechnology, Center for Advanced Medical ResearchHirosaki University Graduate School of MedicineHirosakiAomoriJapan
| | - Hayato Yamamoto
- Department of UrologyHirosaki University Graduate School of MedicineHirosakiAomoriJapan
| | - Mihoko Sutoh Yoneyama
- Department of Cancer Immunology and Cell BiologyOyokyo Kidney Research Institute90 Yamazaki KozawaHirosakiAomoriJapan
| | - Yuki Tobisawa
- Department of UrologyHirosaki University Graduate School of MedicineHirosakiAomoriJapan
| | - Shingo Hatakeyama
- Department of UrologyHirosaki University Graduate School of MedicineHirosakiAomoriJapan
- Department of Advanced Blood Purification TherapyHirosaki University Graduate School of MedicineHirosakiAomoriJapan
| | - Takuma Narita
- Department of UrologyHirosaki University Graduate School of MedicineHirosakiAomoriJapan
- Department of UrologyNational Hospital Organization Hirosaki National HospitalHirosakiAomoriJapan
| | - Hirotake Kodama
- Department of UrologyHirosaki University Graduate School of MedicineHirosakiAomoriJapan
- Department of UrologyTsugaru General HospitalGoshogawaraAomoriJapan
| | - Masaki Momota
- Department of UrologyHirosaki University Graduate School of MedicineHirosakiAomoriJapan
- Department of UrologyMutsu General HospitalMutsuAomoriJapan
| | - Hiroyuki Ito
- Department of UrologyAomori Rosai HospitalHachinoheAomoriJapan
| | - Shintaro Narita
- Department of UrologyAkita University Graduate School of MedicineAkitaJapan
| | - Fumiyasu Tsushima
- Department of RadiologyHirosaki University Graduate School of MedicineHirosakiAomoriJapan
| | - Koji Mitsuzuka
- Department of UrologyTohoku University Graduate School of MedicineSendaiMiyagiJapan
| | - Takahiro Yoneyama
- Department of UrologyHirosaki University Graduate School of MedicineHirosakiAomoriJapan
| | - Yasuhiro Hashimoto
- Department of UrologyHirosaki University Graduate School of MedicineHirosakiAomoriJapan
| | | | | | - Shingo Kakeda
- Department of RadiologyHirosaki University Graduate School of MedicineHirosakiAomoriJapan
| | - Akihiro Ito
- Department of UrologyTohoku University Graduate School of MedicineSendaiMiyagiJapan
| | - Norihiko Tsuchiya
- Department of UrologyYamagata University Faculty of MedicineYamagataJapan
| | - Tomonori Habuchi
- Department of UrologyAkita University Graduate School of MedicineAkitaJapan
| | - Chikara Ohyama
- Department of UrologyHirosaki University Graduate School of MedicineHirosakiAomoriJapan
- Department of Advanced Blood Purification TherapyHirosaki University Graduate School of MedicineHirosakiAomoriJapan
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Constantin T, Savu DA, Bucur Ș, Predoiu G, Constantin MM, Jinga V. The Role and Significance of Bioumoral Markers in Prostate Cancer. Cancers (Basel) 2021; 13:5932. [PMID: 34885045 PMCID: PMC8656561 DOI: 10.3390/cancers13235932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 11/14/2021] [Accepted: 11/22/2021] [Indexed: 11/17/2022] Open
Abstract
The prostate is one of the most clinically accessible internal organs of the genitourinary tract in men. For decades, the only method of screening for prostate cancer (PCa) has been digital rectal examination of 1990s significantly increased the incidence and prevalence of PCa and consequently the morbidity and mortality associated with this disease. In addition, the different types of oncology treatment methods have been linked to specific complications and side effects, which would affect the patient's quality of life. In the first two decades of the 21st century, over-detection and over-treatment of PCa patients has generated enormous costs for health systems, especially in Europe and the United States. The Prostate Specific Antigen (PSA) is still the most common and accessible screening blood test for PCa, but with low sensibility and specificity at lower values (<10 ng/mL). Therefore, in order to avoid unnecessary biopsies, several screening tests (blood, urine, or genetic) have been developed. This review analyzes the most used bioumoral markers for PCa screening and also those that could predict the evolution of metastases of patients diagnosed with PCa.
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Affiliation(s)
- Traian Constantin
- Faculty of General Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (T.C.); (G.P.); (V.J.)
- Department of Urology, “Prof. Dr. Theodor Burghele” Hospital, 050659 Bucharest, Romania
| | - Diana Alexandra Savu
- Department of Urology, “Prof. Dr. Theodor Burghele” Hospital, 050659 Bucharest, Romania
| | - Ștefana Bucur
- Faculty of General Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (T.C.); (G.P.); (V.J.)
- IInd Department of Dermatology, Colentina Clinical Hospital, 020125 Bucharest, Romania
| | - Gabriel Predoiu
- Faculty of General Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (T.C.); (G.P.); (V.J.)
- Department of Urology, “Prof. Dr. Theodor Burghele” Hospital, 050659 Bucharest, Romania
| | - Maria Magdalena Constantin
- Faculty of General Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (T.C.); (G.P.); (V.J.)
- IInd Department of Dermatology, Colentina Clinical Hospital, 020125 Bucharest, Romania
| | - Viorel Jinga
- Faculty of General Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (T.C.); (G.P.); (V.J.)
- Department of Urology, “Prof. Dr. Theodor Burghele” Hospital, 050659 Bucharest, Romania
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Chang EK, Gadzinski AJ, Nyame YA. Blood and urine biomarkers in prostate cancer: Are we ready for reflex testing in men with an elevated prostate-specific antigen? Asian J Urol 2021; 8:343-353. [PMID: 34765442 PMCID: PMC8566358 DOI: 10.1016/j.ajur.2021.06.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 05/17/2021] [Accepted: 05/26/2021] [Indexed: 10/28/2022] Open
Abstract
Objective There is no consensus on the role of biomarkers in determining the utility of prostate biopsy in men with elevated prostate-specific antigen (PSA). There are numerous biomarkers such as prostate health index, 4Kscore, prostate cancer antigen 3, ExoDX, SelectMDx, and Mi-Prostate Score that may be useful in this decision-making process. However, it is unclear whether any of these tests are accurate and cost-effective enough to warrant being a widespread reflex test following an elevated PSA. Our goal was to report on the clinical utility of these blood and urine biomarkers in prostate cancer screening. Methods We performed a systematic review of studies published between January 2000 and October 2020 to report the available parameters and cost-effectiveness of the aforementioned diagnostic tests. We focus on the negative predictive value, the area under the curve, and the decision curve analysis in comparing reflexive tests due to their relevance in evaluating diagnostic screening tests. Results Overall, the biomarkers are roughly equivalent in predictive accuracy. Each test has additional clinical utility to the current diagnostic standard of care, but the added benefit is not substantial to justify using the test reflexively after an elevated PSA. Conclusions Our findings suggest these biomarkers should not be used in binary fashion and should be understood in the context of pre-existing risk predictors, patient's ethnicity, cost of the test, patient life-expectancy, and patient goals. There are more recent diagnostic tools such as multi-parametric magnetic resonance imaging, polygenic single-nucleotide panels, IsoPSA, and miR Sentinel tests that are promising in the realm of prostate cancer screening and need to be investigated further to be considered a consensus reflexive test in the setting of prostate cancer screening.
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Affiliation(s)
- Edward K Chang
- Department of Urology, University of Washington Medical Center, Seattle, WA, USA
| | - Adam J Gadzinski
- Department of Urology, University of Washington Medical Center, Seattle, WA, USA
| | - Yaw A Nyame
- Department of Urology, University of Washington Medical Center, Seattle, WA, USA.,Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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Tan GG, Xu C, Zhong WK, Wang CY. miR-184 delays cell proliferation, migration and invasion in prostate cancer by directly suppressing DLX1. Exp Ther Med 2021; 22:1163. [PMID: 34504608 PMCID: PMC8393589 DOI: 10.3892/etm.2021.10597] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Accepted: 09/04/2019] [Indexed: 11/25/2022] Open
Abstract
A number of previous studies have reported that dysregulated miR-184 expression is associated with the development of cancer. The aim of the present study was to investigate the role of miR-184 in prostate cancer (PC) and the mechanism underlying its effects. Data from human tumor tissue samples were collected from The CEancer Genome Atlas to determine the expression levels of miR-184 and DLX1. The miR-184 mimic and pcDNA3.1-DLX1 plasmid were utilized to induce overexpression of miR-184 and DLX1 in Du145 cells, respectively. Cell Counting Kit-8, wound healing and Transwell assays were performed to examine the effects of miR-184 on the aggressiveness of PC cells. Dual-luciferase reporter gene assay was used to investigate the association between miR-184 and DLX1, and reverse transcription-quantitative PCR and western blot analyses were utilized to determine the mRNA and protein levels. miR-184 expression was found to be downregulated whereas DLX1 was upregulated in PC tissues compared with normal prostate tissues. Cell propagation, migration and invasion were all inhibited by miR-184 upregulation in Du145 cells. Dual luciferase reporter assay confirmed the association between miR-184 and DLX1. The inhibitory effect of miR-184 mimic on cell behaviors was reversed by upregulation of DLX1. These findings suggest that miR-184 plays a beneficial role in suppressing the tumorigenesis of PC by directly targeting DLX1, and it may represent a potential therapeutic strategy for PC.
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Affiliation(s)
- Gui-Geng Tan
- Department of Urology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272100, P.R. China
| | - Chang Xu
- Department of Urology, Yanzhou People's Hospital, Jining, Shandong 272100, P.R. China
| | - Wei-Kang Zhong
- Operating Room Department, Affiliated Hospital of Jining Medical University, Jining, Shandong 272100, P.R. China
| | - Chuan-Yun Wang
- Department of Urinary Surgery, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China
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Goel S, Bhatia V, Kundu S, Biswas T, Carskadon S, Gupta N, Asim M, Morrissey C, Palanisamy N, Ateeq B. Transcriptional network involving ERG and AR orchestrates Distal-less homeobox-1 mediated prostate cancer progression. Nat Commun 2021; 12:5325. [PMID: 34493733 PMCID: PMC8423767 DOI: 10.1038/s41467-021-25623-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 08/20/2021] [Indexed: 02/07/2023] Open
Abstract
Distal-less homeobox-1 (DLX1) is a well-established non-invasive biomarker for prostate cancer (PCa) diagnosis, however, its mechanistic underpinnings in disease pathobiology are not known. Here, we reveal the oncogenic role of DLX1 and show that abrogating its function leads to reduced tumorigenesis and metastases. We observed that ~60% of advanced-stage and metastatic patients display higher DLX1 levels. Moreover, ~96% of TMPRSS2-ERG fusion-positive and ~70% of androgen receptor (AR)-positive patients show elevated DLX1, associated with aggressive disease and poor survival. Mechanistically, ERG coordinates with enhancer-bound AR and FOXA1 to drive transcriptional upregulation of DLX1 in ERG-positive background. However, in ERG-negative context, AR/AR-V7 and FOXA1 suffice to upregulate DLX1. Notably, inhibiting ERG/AR-mediated DLX1 transcription using BET inhibitor (BETi) or/and anti-androgen drugs reduce its expression and downstream oncogenic effects. Conclusively, this study establishes DLX1 as a direct-target of ERG/AR with an oncogenic role and demonstrates the clinical significance of BETi and anti-androgens for DLX1-positive patients.
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Affiliation(s)
- Sakshi Goel
- grid.417965.80000 0000 8702 0100Molecular Oncology Laboratory, Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, U.P. India
| | - Vipul Bhatia
- grid.417965.80000 0000 8702 0100Molecular Oncology Laboratory, Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, U.P. India
| | - Sushmita Kundu
- grid.417965.80000 0000 8702 0100Molecular Oncology Laboratory, Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, U.P. India
| | - Tanay Biswas
- grid.417965.80000 0000 8702 0100Molecular Oncology Laboratory, Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, U.P. India
| | - Shannon Carskadon
- grid.239864.20000 0000 8523 7701Vattikuti Urology Institute, Department of Urology, Henry Ford Health System, Detroit, MI USA
| | - Nilesh Gupta
- grid.239864.20000 0000 8523 7701Department of Pathology, Henry Ford Health System, Detroit, MI USA
| | - Mohammad Asim
- grid.5475.30000 0004 0407 4824Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Colm Morrissey
- grid.34477.330000000122986657Department of Urology, University of Washington, Seattle, WA USA
| | - Nallasivam Palanisamy
- grid.239864.20000 0000 8523 7701Vattikuti Urology Institute, Department of Urology, Henry Ford Health System, Detroit, MI USA
| | - Bushra Ateeq
- grid.417965.80000 0000 8702 0100Molecular Oncology Laboratory, Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, U.P. India ,grid.417965.80000 0000 8702 0100The Mehta Family Center for Engineering in Medicine, Indian Institute of Technology Kanpur, Kanpur, U.P. India
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Li Q, Xu K, Tian J, Lu Z, Pu J. MiR-129-5p/DLX1 signalling axis mediates functions of prostate cancer during malignant progression. Andrologia 2021; 53:e14230. [PMID: 34472106 DOI: 10.1111/and.14230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 08/16/2021] [Accepted: 08/18/2021] [Indexed: 11/30/2022] Open
Abstract
We mainly corroborated the potential mechanism of DLX1 and miR-129-5p in prostate cancer cells. DLX1 was upregulated in cancer cells according to qRT-PCR assay. We evaluated the functional changes of the transfected cells via Transwell assay, CCK-8 assay and wound healing assay. DLX1 was confirmed as a cancer promoter. In addition, qRT-PCR showed down-regulated miR-129-5p expression in prostate cancer. We further used dual-luciferase reporter detection to elucidate the targeting between these two genes. The inhibition of miR-129-5p on tumour was verified. Besides, co-transfection of oe-DLX1 and miR-129-5p mimics attenuated this inhibition. These data demonstrated functions of DLX1/miR-129-5p axis in prostate cancer: miR-129-5p hindered the biological functions of cancer cells via inhibiting DLX1 expression. We provide a novel biomarker for prostate cancer.
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Affiliation(s)
- Qi Li
- Department of Urology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
| | - Ke Xu
- Department of Urology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
| | - Jianguo Tian
- Department of Urology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
| | - Zhicheng Lu
- Department of Urology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
| | - Jianming Pu
- Department of Urology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
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Boerrigter E, Benoist GE, van Oort IM, Verhaegh GW, van Hooij O, Groen L, Smit F, Oving IM, de Mol P, Smilde TJ, Somford DM, Mehra N, Schalken JA, van Erp NP. Liquid biopsy reveals KLK3 mRNA as a prognostic marker for progression free survival in patients with metastatic castration-resistant prostate cancer undergoing first-line abiraterone acetate and prednisone treatment. Mol Oncol 2021; 15:2453-2465. [PMID: 33650292 PMCID: PMC8410566 DOI: 10.1002/1878-0261.12933] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 02/12/2021] [Accepted: 02/26/2021] [Indexed: 12/22/2022] Open
Abstract
Circulating RNAs extracted from liquid biopsies represent a promising source of cancer- and therapy-related biomarkers. We screened whole blood from patients with metastatic castration-resistant prostate cancer (mCRPC) following their first-line treatment with abiraterone acetate and prednisone (AA-P) to identify circulating RNAs that may correlate with progression-free survival (PFS). In a prospective multicenter observational study, 53 patients with mCRPC were included after they started first-line AA-P treatment. Blood was drawn at baseline, 1, 3, and 6 months after treatment initiation. The levels of predefined circulating RNAs earlier identified as being upregulated in patients with mCRPC (e.g., microRNAs, long noncoding RNAs, and mRNAs), were analyzed. Uni- and multivariable Cox regression and Kaplan-Meier analyses were used to analyze the prognostic value of the various circulating RNAs for PFS along treatment. Detectable levels of kallikrein-related peptidase 3 (KLK3) mRNA at baseline were demonstrated to be an independent prognostic marker for PFS (201 vs 501 days, P = 0.00054). Three months after AA-P treatment initiation, KLK3 could not be detected in the blood of responding patients, but was still detectable in 56% of the patients with early progression. Our study confirmed that KLK3 mRNA detection in whole blood is an independent prognostic marker in mCRPC patients receiving AA-P treatment. Furthermore, the levels of circulating KLK3 mRNA in patients receiving AA-P treatment might reflect treatment response or early signs of progression.
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Affiliation(s)
- Emmy Boerrigter
- Department of PharmacyRadboud University Medical CenterRadboud Institute for Health SciencesNijmegenthe Netherlands
| | - Guillemette E. Benoist
- Department of PharmacyRadboud University Medical CenterRadboud Institute for Health SciencesNijmegenthe Netherlands
| | - Inge M. van Oort
- Department of UrologyRadboud University Medical CenterRadboud Institute for Molecular Life SciencesNijmegenthe Netherlands
| | - Gerald W. Verhaegh
- Department of UrologyRadboud University Medical CenterRadboud Institute for Molecular Life SciencesNijmegenthe Netherlands
| | - Onno van Hooij
- Department of UrologyRadboud University Medical CenterRadboud Institute for Molecular Life SciencesNijmegenthe Netherlands
| | - Levi Groen
- Department of UrologyRadboud University Medical CenterRadboud Institute for Molecular Life SciencesNijmegenthe Netherlands
| | | | - Irma M. Oving
- Department of Medical OncologyZiekenhuisgroep TwenteAlmelothe Netherlands
| | - Pieter de Mol
- Department of Medical OncologyGelderse Vallei HospitalEdethe Netherlands
| | - Tineke J. Smilde
- Department of Medical OncologyJeroen Bosch Hospital‘s Hertogenboschthe Netherlands
| | | | - Niven Mehra
- Deparment of Medical OncologyRadboud University Medical CenterNijmegenthe Netherlands
| | - Jack A. Schalken
- Department of UrologyRadboud University Medical CenterRadboud Institute for Molecular Life SciencesNijmegenthe Netherlands
| | - Nielka P. van Erp
- Department of PharmacyRadboud University Medical CenterRadboud Institute for Health SciencesNijmegenthe Netherlands
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46
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Garrido MM, Bernardino RM, Marta JC, Holdenrieder S, Guimarães JT. Tumour markers of prostate cancer: The post-PSA era. Ann Clin Biochem 2021; 59:46-58. [PMID: 34463154 DOI: 10.1177/00045632211041890] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Although PSA-based prostate cancer (PCa) screening had a positive impact in reducing PCa mortality, it also led to overdiagnosis, overtreatment and to a significant number of unnecessary biopsies. In the post-PSA era, new biomarkers have emerged that can complement the information given by PSA, towards a better cancer diagnostic specificity, and also allow a better estimate of the aggressiveness of the disease and its clinical outcome. That means those markers have the potential to assist the clinician in the decision-making processes, such as whether or not to perform a biopsy, and to make the best treatment choice among the new therapeutic options available, including active surveillance (AS) in lower risk disease. In this article, we will review several of those more recent diagnostic markers (4Kscore®, [-2]proPSA and Prostate Health Index (PHI), SelectMDx®, ConfirmMDx®, Progensa® Prostate Cancer Antigen 3, Mi-Prostate Score, ExoDx™ Prostate Test, the Stockholm-3 test and ERSPC risk calculators) and prognostic markers (OncotypeDX® Genomic Prostate Score, Prolaris®, Decipher® and ProMark®). We will also address some new liquid biopsy approaches - circulating tumour cells and cell-free DNA (cfDNA) - with a potential role in metastatic castration-resistant PCa and will briefly give some future perspectives, mostly outlooking epigenetic markers.
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Affiliation(s)
- Manuel M Garrido
- Department of Clinical Pathology, 90463Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal.,Department of Laboratory Medicine, 37811Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Rui M Bernardino
- Department of Urology, 90463Centro Hospitalar Universitário de Lisboa central, Lisbon, Portugal
| | - José C Marta
- Department of Clinical Pathology, 90463Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
| | - Stefan Holdenrieder
- Institute of Laboratory Medicine, Munich Biomarker Research Center, 14924Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
| | - João T Guimarães
- Department of Clinical Pathology, Centro Hospitalar Universitário de São João, Porto, Portugal.,Department of Biomedicine, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.,EPIUnit, Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
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47
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Eyrich NW, Morgan TM, Tosoian JJ. Biomarkers for detection of clinically significant prostate cancer: contemporary clinical data and future directions. Transl Androl Urol 2021; 10:3091-3103. [PMID: 34430413 PMCID: PMC8350244 DOI: 10.21037/tau-20-1151] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 04/23/2021] [Indexed: 12/15/2022] Open
Abstract
Use of serum prostate-specific antigen (PSA) testing for early detection of prostate cancer appears to reduce cancer-specific mortality. Due to the limited specificity of PSA for clinically significant [Grade Group (GG) ≥2] cancer, however, screening carries substantial risks, including frequent unnecessary prostate biopsies and overdetection of non-aggressive cancers. To that end, serum and urine biomarkers with improved specificity for GG ≥2 cancer have been proposed for clinical use following PSA. In the current article, we present clinical validation data for five such biomarkers: PHI, 4Kscore, SelectMDx, ExoDx, and MPS. For all studies, we specify the study population (overall biopsy referral vs. pre-specified PSA ranges), previous biopsy status (biopsy-naïve vs. previous negative biopsy), and the proportion of subjects diagnosed with GG ≥2 cancer. Outcomes include test performance characteristics: sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Published data were used to compute the number of unnecessary biopsies avoided and number of GG ≥2 cancers missed if the biomarker had been used clinically to select for prostate biopsy. The evidence review is preceded by a primer on these and other clinically-relevant summary statistics.
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Affiliation(s)
| | - Todd M Morgan
- Department of Urology, University of Michigan, Ann Arbor, MI, USA.,Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.,Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Jeffrey J Tosoian
- Department of Urology, University of Michigan, Ann Arbor, MI, USA.,Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.,Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA
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48
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Nair SV, Madhulaxmi, Thomas G, Ankathil R. Next-Generation Sequencing in Cancer. J Maxillofac Oral Surg 2021; 20:340-344. [PMID: 34408360 DOI: 10.1007/s12663-020-01462-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Accepted: 09/28/2020] [Indexed: 11/28/2022] Open
Abstract
Objective In this article, we provide a gestalt idea about NGS technologies and their applications in cancer research and molecular diagnosis. Background Next-generation sequencing (NGS) advancements like DNA sequencing and RNA sequencing allow uncovering of genomic, transcriptomic, and epigenomic scenes of individual malignant growths. An assortment of genomic abnormalities can be screened at the same time, for example common and uncommon variations, auxiliary variations like insertions and deletions, copy-number variation, and fusion transcripts. Conclusion NGS innovations together with bioinformatics investigation, which extend our insight, are progressively used to analyze multiple genes in a cost-effective way and have been applied in examining clinical cancer samples and offering NGS-based molecular diagnosis. Application NGS is progressively significant as a device for the diagnosis of cancers.
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Affiliation(s)
- S Vinod Nair
- Department of Oral and Maxillofacial Surgery, P.M.S Dental College, Vattapara, Trivandrum, India
| | - Madhulaxmi
- Department of Oral and Maxillofacial Surgery, Saveetha Dental College, Chennai, India
| | - Gigi Thomas
- Community Medicine, Regional Cancer Centre, Trivandrum, India
| | - Ravindran Ankathil
- Human Genome Centre, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, George Town, Malaysia
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49
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A 25-year perspective on evaluation and understanding of biomarkers in urologic cancers. Urol Oncol 2021; 39:602-617. [PMID: 34315659 DOI: 10.1016/j.urolonc.2021.06.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 06/17/2021] [Indexed: 12/15/2022]
Abstract
The past 25 years have witnessed an explosion of investigative attempts to identify clinically useful biomarkers which can have meaningful impacts for patients with urologic cancers. However, in spite of the enormous amount of research aiming to identify markers with the hope of impacting patient care, only a handful have proven to have true clinical utility. Improvements in targeted imaging, pan-omics evaluation, and genetic sequencing at the tissue and single-cell levels have yielded many potential targets for continued biomarker investigation. This article, as one in this series for the 25th Anniversary Issue of Urologic Oncology: Seminars and Original Investigations, serves to give a perspective on our progress and failures over the past quarter-century in our highest volume urologic cancers: prostate, bladder, and kidney cancers.
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50
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Meehan J, Gray M, Martínez-Pérez C, Kay C, McLaren D, Turnbull AK. Tissue- and Liquid-Based Biomarkers in Prostate Cancer Precision Medicine. J Pers Med 2021; 11:jpm11070664. [PMID: 34357131 PMCID: PMC8306523 DOI: 10.3390/jpm11070664] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/06/2021] [Accepted: 07/13/2021] [Indexed: 12/24/2022] Open
Abstract
Worldwide, prostate cancer (PC) is the second-most-frequently diagnosed male cancer and the fifth-most-common cause of all cancer-related deaths. Suspicion of PC in a patient is largely based upon clinical signs and the use of prostate-specific antigen (PSA) levels. Although PSA levels have been criticised for a lack of specificity, leading to PC over-diagnosis, it is still the most commonly used biomarker in PC management. Unfortunately, PC is extremely heterogeneous, and it can be difficult to stratify patients whose tumours are unlikely to progress from those that are aggressive and require treatment intensification. Although PC-specific biomarker research has previously focused on disease diagnosis, there is an unmet clinical need for novel prognostic, predictive and treatment response biomarkers that can be used to provide a precision medicine approach to PC management. In particular, the identification of biomarkers at the time of screening/diagnosis that can provide an indication of disease aggressiveness is perhaps the greatest current unmet clinical need in PC management. Largely through advances in genomic and proteomic techniques, exciting pre-clinical and clinical research is continuing to identify potential tissue, blood and urine-based PC-specific biomarkers that may in the future supplement or replace current standard practices. In this review, we describe how PC-specific biomarker research is progressing, including the evolution of PSA-based tests and those novel assays that have gained clinical approval. We also describe alternative diagnostic biomarkers to PSA, in addition to biomarkers that can predict PC aggressiveness and biomarkers that can predict response to certain therapies. We believe that novel biomarker research has the potential to make significant improvements to the clinical management of this disease in the near future.
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Affiliation(s)
- James Meehan
- Translational Oncology Research Group, Institute of Genetics and Cancer, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK; (C.M.-P.); (C.K.); (A.K.T.)
- Correspondence:
| | - Mark Gray
- The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Midlothian EH25 9RG, UK;
| | - Carlos Martínez-Pérez
- Translational Oncology Research Group, Institute of Genetics and Cancer, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK; (C.M.-P.); (C.K.); (A.K.T.)
- Breast Cancer Now Edinburgh Research Team, Institute of Genetics and Cancer, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK
| | - Charlene Kay
- Translational Oncology Research Group, Institute of Genetics and Cancer, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK; (C.M.-P.); (C.K.); (A.K.T.)
- Breast Cancer Now Edinburgh Research Team, Institute of Genetics and Cancer, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK
| | - Duncan McLaren
- Edinburgh Cancer Centre, Western General Hospital, NHS Lothian, Edinburgh EH4 2XU, UK;
| | - Arran K. Turnbull
- Translational Oncology Research Group, Institute of Genetics and Cancer, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK; (C.M.-P.); (C.K.); (A.K.T.)
- Breast Cancer Now Edinburgh Research Team, Institute of Genetics and Cancer, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK
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