Article
Genetics & Heredity
Xiaodong Lu, Ka-wing Fong, Fang Wang, Galina Gritsina, Sylvan C. Baca, Jacob E. Berchuck, Jenny Ross, Eva Corey, Navdeep Chandel, William J. Catalona, Ximing Yang, Matthew L. Freedman, Jonathan C. Zhao, Jindan Yu, Lourdes T. Brea, Sandor Spisak, CoIm Morrissey
Summary: The study reveals that HOXB13 suppresses lipogenic transcriptional program in prostate cancer through HDAC3 recruitment, which inhibits tumor metastasis. Loss or mutation of HOXB13 leads to lipid accumulation in PCa cells, promoting cell motility and tumor metastasis. This study provides important insights into the roles of HOXB13 in prostate cancer progression and metastasis.
Article
Oncology
Duy T. Nguyen, Wei Yang, Arun Renganathan, Cody Weimholt, Duminduni H. Angappulige, Thanh Nguyen, Robert W. Sprung, Gerald L. Andriole, Eric H. Kim, Nupam P. Mahajan, Kiran Mahajan
Summary: This study reveals that HOXB13 exacerbates the antagonism of androgen receptor (AR) in castration-resistant prostate cancers (CRPC), and identifies a novel lysine 13 (K13) acetylation in HOXB13. Acetylated K13-HOXB13 serves as a clinical biomarker for the development of CRPC and promotes the expression of lineage, diagnostic, CRPC-promoting, and angiogenesis genes. The HOXB13 target ACK1 could be a potential therapeutic target for inhibiting CRPC growth.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Radhika A. Patel, Erolcan Sayar, Ilsa Coleman, Martine P. Roudier, Brian Hanratty, Jin-Yih Low, Neha Jaiswal, Azra Ajkunic, Ruth Dumpit, Caner Ercan, Nina Salama, Valerie P. O'Brien, William B. Isaacs, Jonathan Epstein, Angelo M. De Marzo, Bruce J. Trock, Jun Luo, W. Nathaniel Brennen, Maria Tretiakova, Funda Vakar-Lopez, Lawrence D. True, David W. Goodrich, Eva Corey, Colm Morrissey, Peter S. Nelson, Paula J. Hurley, Roman Gulati, Michael C. Haffner
Summary: This study investigated the expression pattern of HOXB13 in prostate development and cancer progression. HOXB13 was found to be more highly expressed in localized prostate cancers and retained in advanced metastatic prostate cancers. The expression of HOXB13 was reduced in tumors with evidence of lineage plasticity, but most androgen receptor-negative castration-resistant prostate cancers and neuroendocrine prostate cancers still had detectable levels of HOXB13. HOXB13 showed greater sensitivity in detecting advanced metastatic prostate cancers compared to the commonly used marker NKX3.1. HOXB13 immunohistochemistry had high sensitivity and specificity for confirming the prostatic origin of tumors in clinical samples.
JOURNAL OF PATHOLOGY
(2023)
Article
Oncology
Ericka M. Sohlberg, I-Chun Thomas, Jaden Yang, Kristopher Kapphahn, Kyla N. Velaer, Mary K. Goldstein, Todd H. Wagner, Glenn M. Chertow, James D. Brooks, Chirag J. Patel, Manisha Desai, John T. Leppert
Summary: This study utilized the laboratory-wide association study (LWAS) method to analyze the associations between routine laboratory tests and survival in veterans with prostate cancer. The researchers identified multiple laboratory tests associated with survival, which can be used to inform the design of clinical trials and aid in shared decision making for patients.
Article
Oncology
Min Joon Lee, Viranda H. Jayalath, Wei Xu, Lin Lu, Stephen J. Freedland, Neil E. Fleshner, Girish S. Kulkarni, Antonio Fineni, Theodorus H. van Der Kwast, Robert J. Hamilton
Summary: The relationship between metformin use and prostate cancer risk is controversial, with metformin use associated with increased risk of high-grade and overall prostate cancer. SNPs involved in metformin metabolism did not modify disease risk association, but two SNPs from the GWAS study did.
PROSTATE CANCER AND PROSTATIC DISEASES
(2021)
Article
Urology & Nephrology
Mark N. Brook, Holly Ni Raghallaigh, Koveela Govindasami, Tokhir Dadaev, Reshma Rageevakumar, Diana Keating, Nafisa Hussain, Andrea Osborne, Artitaya Lophatananon, Kenneth R. Muir, Zsofia Kote-Jarai, Rosalind A. Eeles
Summary: A family history of prostate cancer is associated with an increased risk of developing the disease. This study examines how the number, degree, and age of relatives with prostate cancer are related to overall survival and prostate cancer-specific survival in prostate cancer patients.
Article
Urology & Nephrology
Burcu F. Darst, Raymond Hughley, Aaron Pfennig, Ujani Hazra, Caoqi Fan, Peggy Wan, Xin Sheng, Lucy Xia, Caroline Andrews, Fei Chen, Sonja Berndt, Zsofia Kote-Jarai, Koveela Govindasami, Jeannette T. Bensen, Sue A. Ingles, Benjamin A. Rybicki, Barbara Nemesure, Esther M. John, Jay H. Fowke, Chad D. Huff, Sara S. Strom, William B. Isaacs, Jong Y. Park, Wei Zheng, Elaine A. Ostrander, Patrick C. Walsh, John Carpten, Thomas A. Sellers, Kosj Yamoah, Adam B. Murphy, Maureen Sanderson, Dana C. Crawford, Susan M. Gapstur, William S. Bush, Melinda C. Aldrich, Olivier Cussenot, Gyorgy Petrovics, Jennifer Cullen, Christine Neslund-Dudas, Rick A. Kittles, Jianfeng Xu, Mariana C. Stern, Anand P. Chokkalingam, Luc Multigner, Marie-Elise Parent, Florence Menegaux, Geraldine Cancel-Tassin, Adam S. Kibel, Eric A. Klein, Phyllis J. Goodman, Janet L. Stanford, Bettina F. Drake, Jennifer J. Hu, Peter E. Clark, Pascal Blanchet, Graham Casey, Anselm J. M. Hennis, Alexander Lubwama, Ian M. Thompson, Robin J. Leach, Susan M. Gundell, Loreall Pooler, James L. Mohler, Elizabeth T. H. Fontham, Gary J. Smith, Jack A. Taylor, Laurent Brureau, William J. Blot, Richard Biritwum, Evelyn Tay, Ann Truelove, Shelley Niwa, Yao Tettey, Rohit Varma, Roberta McKean-Cowdin, Mina Torres, Mohamed Jalloh, Serigne Magueye Gueye, Lamine Niang, Olufemi Ogunbiyi, Michael Oladimeji Idowu, Olufemi Popoola, Akindele O. Adebiyi, Oseremen Aisuodionoe-Shadrach, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa-Abrahams, Edward D. Yeboah, James E. Mensah, Andrew Anthony Adjei, Halimatou Diop, Michael B. Cook, Stephen J. Chanock, Stephen Watya, Rosalind A. Eeles, Charleston W. K. Chiang, Joseph Lachance, Timothy R. Rebbeck, David Conti, Christopher A. Haiman
Summary: A specific germline deletion variant in HOXB13 (X285K) was found to be associated with an increased risk of prostate cancer in men of West African ancestry. This variant was more strongly associated with aggressive and advanced disease. Understanding who carries this variant can inform prostate cancer screening in men of West African ancestry.
Article
Nutrition & Dietetics
Wei Qi Loh, Xin Yin, Rie Kishida, Sin Eng Chia, Choon Nam Ong, Wei Jie Seow
Summary: The purpose of this study was to investigate the association between different forms of vitamin A and E and the risk of prostate cancer, as well as identify potential effect modifiers. The researchers measured the serum concentrations of 15 different forms of vitamins A and E in prostate cancer patients and control subjects using a high-performance liquid chromatography technique. The results showed that several forms of vitamin A and E were positively associated with prostate cancer risk, with stronger associations observed in smokers and regular alcohol drinkers. The findings provide important insights into the etiology of prostate cancer.
Article
Oncology
Yonghong Chen, Catherine R. Dufour, Lingwei Han, Ting Li, Hui Xia, Vincent Giguere
Summary: Dysregulation of mTOR signaling is critical in promoting prostate cancer growth. This study reveals that mTOR interacts with and phosphorylates HOXB13, leading to the regulation of a specific gene program with oncogenic implications in prostate cancer. These findings uncover a previously unknown molecular cascade and provide a potential therapeutic avenue for advanced prostate cancer management.
MOLECULAR CANCER RESEARCH
(2023)
Article
Genetics & Heredity
Nicholas B. Larson, Shannon K. McDonnell, Zachary Fogarty, Yuanhang Liu, Amy J. French, Lori S. Tillmans, John C. Cheville, Liang Wang, Daniel J. Schaid, Stephen N. Thibodeau
Summary: Large-scale genome-wide association studies have identified hundreds of single-nucleotide polymorphisms associated with increased risk of prostate cancer (PrCa). However, the relationship between PrCa risk genetics and microRNA expression dysregulation is understudied. This study performed a microRNA transcriptome-wide association study of PrCa risk and identified significant associations between microRNA expression and PrCa risk.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Siyuan Cheng, Shu Yang, Yingli Shi, Runhua Shi, Yunshin Yeh, Xiuping Yu
Summary: HOX gene-encoded homeobox proteins control body patterning during embryonic development; specific expression pattern of HOX genes may correspond to tissue identity. Our study found that NEPCa tumors lose their prostate identities but do not gain new tissue identities, indicating their anaplastic nature. Additionally, treatment with all trans retinoic acid (ATRA) can potentially revert reduced HOXB13 expression in NEPCa cells, suggesting ATRA as a therapeutic agent for NEPCa tumors.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Chaoran Ma, Xiaoyu Wang, James Y. Dai, Constance Turman, Peter Kraft, Konrad H. Stopsack, Massimo Loda, Andreas Pettersson, Lorelei A. Mucci, Janet L. Stanford, Kathryn L. Penney
Summary: This study investigated the germline genetic variants associated with TMPRSS2:ERG fusion status in prostate cancer cases. The findings suggest that tumors with TMPRSS2:ERG fusion have a different genetic etiology compared to fusion negative cases. The study identified several SNPs at known prostate cancer risk loci that were differentially associated with the risk of developing prostate tumors with or without the gene fusion.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Article
Medicine, Research & Experimental
Thiago Vidotto, Eddie L. Imada, Farzana Faisal, Sanjana Murali, Adrianna A. Mendes, Harsimar Kaur, Siqun Zheng, Jianfeng Xu, Edward M. Schaeffer, William B. Isaacs, Karen S. Sfanos, Luigi Marchionni, Tamara L. Lotan
Summary: The genomic and immune landscapes of prostate cancer differ by self-identified race. Specific copy number alterations and Treg infiltration are associated with genetic ancestry and outcome in primary prostate cancer.
Article
Multidisciplinary Sciences
Mariana Bezamat, Scott Rothenberger, Alexandre R. Vieira
Summary: Early-stage cancer diagnosis is crucial for improving survival rates. This study found that a genetic variant in ERN1 (rs196929) is associated with increased risk of skin cancer, breast cancer, and male reproductive system cancers.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Rong Na, Jun Wei, Chris J. Sample, Marta Gielzak, Sodam Choi, Kathleen A. Cooney, Daniel Rabizadeh, Patrick C. Walsh, Lilly S. Zheng, Jianfeng Xu, William B. Isaacs
Summary: A novel HOXB13 variant, X285K, was found in African-American men with prostate cancer, showing an association with increased risk of clinically significant and early onset PCa. This variant, although rare in the population, holds translational potential as an important susceptibility marker in high-risk African-American population.
BRITISH JOURNAL OF CANCER
(2022)
Article
Gastroenterology & Hepatology
Anders Forss, Mark Clements, Par Myrelid, Hans Strid, Charlotte Soderman, Agnieszka Wagner, David Andersson, Fredrik Hjelm, Ola Olen, Jonas Halfvarson, Jonas F. Ludvigsson
Summary: This study demonstrates the long-term clinical effectiveness of ustekinumab in patients with active Crohn's disease, as well as its improvement in Health-related Quality of Life (HRQoL) measures.
DIGESTIVE DISEASES AND SCIENCES
(2023)
Article
Health Care Sciences & Services
Thomas Piggott, Miranda W. Langendam, Elena Parmelli, Jan Adolfsson, Elie A. Akl, David Armstrong, Jeffrey Braithwaite, Romina Brignardello-Petersen, Jan Brozek, Markus Follmann, Ina Kopp, Joerg J. Meerpohl, Luciana Neamtiu, Monika Nothacker, Amir Qaseem, Paolo Giorgi Rossi, Zuleika Saz-Parkinson, Philip J. van der Wees, Holger J. Schunemann
Summary: The study aimed to develop an extension of the GIN-McMaster Guideline Development Checklist and Tool for the integration of quality assurance and improvement (QAI) schemes with guideline development. A mixed-methods approach was used, incorporating evidence from a systematic review, an expert workshop, and a survey of experts. The result was a 40-item checklist extension, addressing steps for the integration of QAI into guideline development.
JOURNAL OF CLINICAL EPIDEMIOLOGY
(2023)
Article
Medicine, General & Internal
E. Lin, Hans Garmo, Mieke Van Hemelrijck, Bjorn Zethelius, Par Stattin, Emil Hagstrom, Jan Adolfsson, Danielle Crawley
Summary: This study aimed to evaluate the association between GnRH agonist use, PCa diagnosis, and CVD risk in men with type 2 diabetes. The results showed that men with type 2 diabetes who received GnRH agonist for PCa had an increased risk of CVD and lower blood pressure levels.
Article
Computer Science, Interdisciplinary Applications
Rasmus Kuhr Jensen, Mark Clements, Lars Klingen Gjaerde, Lasse Hjort Jakobsen
Summary: Cure models are useful for analyzing time-to-event data in medical research, estimating the proportion of cured individuals and the event-time distribution of those who are not cured. The R packages cuRe and rstpm2 provide researchers with tools for performing statistical inference using parametric cure models, offering flexibility in fitting different types of cure models.
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
(2022)
Article
Economics
Edna Keeney, Sabina Sanghera, Richard M. Martin, Roman Gulati, Fredrik Wiklund, Eleanor Walsh, Jenny L. Donovan, Freddie Hamdy, David E. Neal, J. Athene Lane, Emma L. Turner, Howard Thom, Mark S. Clements
Summary: Guidelines in the UK, Europe, and North America do not typically recommend population-wide screening for prostate cancer, but prostate-specific antigen-based screening can reduce prostate cancer-specific mortality. A study assessed the cost effectiveness of eight potential screening strategies in the UK, finding that a one-off screening at age 50 may be the most cost-effective option.
Article
Oncology
E. Lin, Hans Garmo, Emil Hagstrom, Mieke Van Hemelrijck, Jan Adolfsson, Par Stattin, Bjorn Zethelius, Danielle Crawley
Summary: This study investigated the association between the use of GnRH in prostate cancer patients with type 2 diabetes mellitus and atherogenic dyslipidaemia. The results showed that GnRH treatment was associated with increased atherogenic lipids, indicating the need for caution when using GnRH in patients with diabetes.
BRITISH JOURNAL OF CANCER
(2023)
Article
Statistics & Probability
Benjamin Christoffersen, Behrang Mahjani, Mark Clements, Hedvig Kjellstrom, Keith Humphreys
Summary: The generalized linear mixed model with the probit link function faces computational challenges in binary outcomes with many random effects. We propose an extended importance sampler that incorporates a gradient and Hessian approximation to estimate heritability and related effects from family data. Additionally, a graph-based method is suggested to simplify the likelihood when dealing with a large number of individuals in each family. Simulation studies demonstrate that the proposed method is significantly faster, maintains efficiency, and provides reliable confidence intervals. We also apply the method to a large study on obsessive-compulsive disorder, yielding similar results to previous analyses but with improved speed. Supplementary data for this article are available online.
JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS
(2023)
Article
Oncology
Shuang Hao, Andrea Discacciati, Martin Eklund, Emelie Heintz, Ellinor Ostensson, K. Miriam Elfstrom, Mark S. Clements, Tobias Nordstrom
Summary: An economic evaluation study found that combining PSA testing with MRI and combined targeted and standard biopsies for prostate cancer screening is more cost-effective than the traditional screening pathway. MRI-based screening reduces the number of biopsies and overdiagnosis and decreases prostate cancer-related deaths compared to standard biopsies.
Review
Pediatrics
Jonas F. Ludvigsson, Jan Adolfsson, Malin Hoistad, Per-Anders Rydelius, Berit Kristroem, Mikael Landen
Summary: This systematic review aims to assess the effects of hormone treatment on psychosocial and mental health, cognition, body composition, and metabolic markers in children with gender dysphoria. The review identified 24 relevant English-language studies, but the evidence was insufficient to evaluate the effects of hormone therapy in these areas. Further research is needed to better understand the impacts of hormone treatment in children with gender dysphoria.
Letter
Oncology
Shuang Hao, Tobias Nordstrom, Mark S. Clements
Meeting Abstract
Urology & Nephrology
Chiara Micoli, Alessio Crippa, Andrea Discacciati, Thorgerdur Palsdottir, Hari Vigneswaran, Markus Aly, Jan Adolfsson, Johan Lindberg, Peter Wiklund, James Thompson, Yvonne Brandberg, Mark Clements, Lars Egevad, Henrik Gronberg, Tobias Nordstrom, Martin Eklund
JOURNAL OF UROLOGY
(2023)
Article
Urology & Nephrology
Anna Lantz, Per Nordlund, Ugo Falagario, Fredrik Joderling, Orhan Ozbek, Mark Clements, Andrea Discacciati, Henrik Gronberg, Martin Eklund, Phillip Stricker, Mark Emberton, Markus Aly, Tobias Nordstrom
Summary: The aim of focal treatments in prostate cancer is to minimize damage to surrounding tissue while treating lesions. Irreversible electroporation (IRE) is a nonthermal technique that shows promise in achieving this. The Prostate Cancer IRE Study (PRIS) is a two-part study comparing IRE with robot-assisted radical prostatectomy (RARP) and radiotherapy, respectively, in men with intermediate-risk prostate cancer. The study will evaluate functional outcomes, as well as secondary objectives such as erectile function and quality of life.
EUROPEAN UROLOGY OPEN SCIENCE
(2023)
Article
Mathematical & Computational Biology
Michael J. Crowther, Patrick Royston, Mark Clements
Summary: In this article, a general parametric AFT model is proposed, with restricted cubic splines used to model the baseline for greater flexibility. The model is extended to accommodate time-dependent acceleration factors, allowing for delayed entry and time-dependent covariates. Simulation evaluations show substantial improvements compared to standard parametric AFT models. Analytical and simulation results also demonstrate the collapsibility of AFT models, indicating their suitability for causal inference. The methods are illustrated using a dataset of breast cancer patients, and efficient, user-friendly software packages in Stata and R are provided.
Meeting Abstract
Economics
E. Y. T. Chen, T. Dahlen, M. Bjorkholm, L. Stenke, E. Ostensson, M. S. Clements, P. W. Dickman
Meeting Abstract
Economics
S. Hao, M. S. Clements