tbuckley/cabot-search huggingface dataset:
Abstract 3282: BMI and other factors in relation to overall survival of female breast cancer in China
Authors: Yunqiu Dong, Franzel J. B. van Duijnhoven, Lu Wang, Ming Wu, Yun Qian, Ellen Kampman
Journal: Cancer Research (2019)

Abstract The aim of this study is to determine the relationship between body mass index(BMI) at diagnosis and various factors including the epidemiologic and clinical factors on survival of female breast cancers. We analysed the data of 653 patients in any stage from the Wuxi Breast Cancer Cohort. Cox Proportional Hazard regression models were conducted to compare the overall survival(OS) outcomes among BMI groups, and adjusted by covariates which yielded a &amp;gt;10% change in the hazard ratios(HRs) estimate, including age, stage, menopause status, physical activity in work. There were significant differences among BMI groups in age(P=0.000), WHR(P =0.000), physical activity in work(P =0.019),red meat intake(P =0.029), oil intake(P =0.000),tumor stage(P =0.021),menopause status(P =0.001). Overweight(OW,BMI=24 to 27.9kg/m2) and obesity(OB, BMI≥28kg/m2) showed better OS comparing with normal weight(NW, BMI=18.5 to 23.9kg/m2)(respectively, adjusted HRs=0.45, 95%CI=0.15 to 1.34, adjusted HRs=0.59,95%CI=0.21 to 1.69), meanwhile underweight(UW, BMI&amp;lt;18.5kg/m2) showed a poorer OS(adjusted HRs=4.65,95%CI=0.93 to 23.37). There was no significant relationship between the BMI and some other factors in OS. In conclusion, the findings of our current study indicate that BMI might play a role in the prognosis of female breast cancer in China, but the evidence was not strong enough. Citation Format: Yunqiu Dong, Franzel J. B. van Duijnhoven, Lu Wang, Ming Wu, Yun Qian, Ellen Kampman. BMI and other factors in relation to overall survival of female breast cancer in China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3282.
Reply to Milan Hora's Letter to the Editor re: Philip S. Macklin, Mark E. Sullivan, Charles R. Tapping, et al. Tumour Seeding in the Tract of Percutaneous Renal Tumour Biopsy: A Report on Seven Cases from a UK Tertiary Referral Centre. Eur Urol 2019;75:861–7
Authors: Philip S. Macklin, Mark E. Sullivan, Charles R. Tapping, Guy M. Webster, Ian S.D. Roberts, Clare L. Verrill, Lisa Browning
Journal: European Urology (2019)
Clinical features and genetic spectrum in Chinese patients with recessive hereditary spastic paraplegia
Authors: Qiao Wei, Hai-Lin Dong, Li-Ying Pan, Cong-Xin Chen, Yang-Tian Yan, Rou-Min Wang, Hong-Fu Li, Zhi-Jun Liu, Qing-Qing Tao, Zhi-Ying Wu
Journal: Translational Neurodegeneration (2019)

Although many causative genes of hereditary spastic paraplegia (HSP) have been uncovered in recent years, there are still approximately 50% of HSP patients without genetically diagnosis, especially in autosomal recessive (AR) HSP patients. Rare studies have been performed to determine the genetic spectrum and clinical profiles of recessive HSP patients in the Chinese population.
Targeting mTOR for cancer therapy
Authors: Hui Hua, Qingbin Kong, Hongying Zhang, Jiao Wang, Ting Luo, Yangfu Jiang
Journal: Journal of Hematology & Oncology (2019)

Mechanistic target of rapamycin (mTOR) is a protein kinase regulating cell growth, survival, metabolism, and immunity. mTOR is usually assembled into several complexes such as mTOR complex 1/2 (mTORC1/2). In cooperation with raptor, rictor, LST8, and mSin1, key components in mTORC1 or mTORC2, mTOR catalyzes the phosphorylation of multiple targets such as ribosomal protein S6 kinase β-1 (S6K1), eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), Akt, protein kinase C (PKC), and type-I insulin-like growth factor receptor (IGF-IR), thereby regulating protein synthesis, nutrients metabolism, growth factor signaling, cell growth, and migration. Activation of mTOR promotes tumor growth and metastasis. Many mTOR inhibitors have been developed to treat cancer. While some of the mTOR inhibitors have been approved to treat human cancer, more mTOR inhibitors are being evaluated in clinical trials. Here, we update recent advances in exploring mTOR signaling and the development of mTOR inhibitors for cancer therapy. In addition, we discuss the mechanisms underlying the resistance to mTOR inhibitors in cancer cells.
The Global Initiative for Asthma (GINA): 25 years later
Authors: Louis-Philippe Boulet, Helen K. Reddel, Eric Bateman, Søren Pedersen, J. Mark FitzGerald, Paul M. O'Byrne
Journal: European Respiratory Journal (2019)

The Global Initiative for Asthma (GINA) was launched in 1993 under the auspices of the National Heart, Lung, and Blood Institute, National Institutes of Health, USA, and the World Health Organization to produce a global strategy on asthma management and prevention. Now constituted as a non-profit entity, it continues to produce, on an annual basis, the most widely cited evidence-based report on the optimal management of asthma in both adults and children intended for global use. Although the GINA Report is often viewed and used as an asthma treatment guideline, it is designed to be a clinically oriented strategy document that supports the development of practice guidelines in different countries and regions. Other GINA products, including the report's pocket guides, teaching slide kits and implementation tools, are also offered free of charge for public use. The GINA Scientific Committee comprises recognised international experts from primary, secondary and tertiary centres of care who are actively involved in both the care of patients and research in asthma. The GINA Assembly is a forum for exchange of scientific information and discussions on initiatives to improve asthma care in various countries, focusing on implementation strategies. GINA plays a role in shaping research on the diagnosis and treatment of asthma and informs the development of point of care practice guides and decision support tools. GINA supports the objectives of raising awareness of asthma and improving access to therapy and quality of care for asthmatic patients, in addition to presenting and promoting continuously updated evidence-based treatment approaches for global use.
常在伴有肺纤维化的系统性硬化症患者中检测到抗 C1q 自身抗体
Authors: C. Liaskos, S. Rentouli, T. Simopoulou, A. Gkoutzourelas, G.L. Norman, A. Brotis, I. Alexiou, C. Katsiari, D.P. Bogdanos, L.I. Sakkas
Journal: British Journal of Dermatology (2019)

系统性硬化症 (SSc) 是一种自身免疫性疾病,它意味着通常负责对抗疾病的身体免疫系统会错误地瞄准身体的健康部位,而SSc患者会产生针对自身组织的抗体(“自身抗体”)。广泛的增厚和瘢痕组织(纤维化)是这种疾病的主要特征,并且原因是胶原蛋白的过度生成。小血管也会发生变化。当纤维化发生在肺(肺纤维化)时,它可以导致高血压动脉进入肺,而这可能会危及生命。这种疾病在女性中比较常见。根据皮肤受累的程度,SSc 可能是局部的,也可能是广泛的。尽管引起 SSc 的原因还没有完全弄清楚,但人们相信其中以这样或那样的方式涉及到许多与这种疾病相关的自身抗体。在另一种名为系统性红斑狼疮的自身免疫性疾病中,确定发现了一种名为“抗‐C1q”的自身抗体,因此,来自希腊和美国的这项研究的目的是研究它们是否也存在于 SSc 中。在这项研究中的 124 名 SSc 患者中,有 16.1% 的患者体内发现了抗‐C1q 自身抗体,其发生频率与第三高的自身抗体(即抗‐RNA 聚合酶 III)一样高。尤其是在男性和散播性 SSc 患者中发现了这种抗体。抗‐C1q 抗体的存在与肺纤维化有关,但与 SSc 的任何其他特征无关。因此,作者认为抗‐C1q 自身抗体可以作为 SSc 患者肺纤维化的一个标志物(信号)。
Abstract 3531: Modular RNA expression analysis using whole transcriptome and targeted analysis in single cells on BD Rhapsody
Authors: Margaret Nakamoto, Gretchen Lam, Christina Chang, Eleen Shum
Journal: Cancer Research (2019)

Abstract Advances in genomics have allowed high-throughput single-cell whole transcriptome analysis (WTA) to enable the discovery of biomarkers and cellular pathways that may be important in diseases. As a complementary tool to WTA, targeted analysis can provide high sensitivity of single cell gene expression data with lower sequencing cost. Here we demonstrate using the BD Rhapsody platform in a modular fashion to generate both WTA and targeted sequencing libraries from the same sample. Utilizing the archivability of the BD Rhapsody beads, we first subsampled a portion of the beads to generate WTA data, from which we identified genes that are important for T cell exhaustion. We then designed a targeted panel to profile the rest of the beads from the same experiment. The study demonstrates the versatility of the BD Rhapsody single cell platform and the ability to conduct different workflows on the same sample. This approach offers flexibility and choice for users in experimental design and allows users to easily transition from novel target discovery to robust data validation using targeted panels. Citation Format: Margaret Nakamoto, Gretchen Lam, Christina Chang, Eleen Shum. Modular RNA expression analysis using whole transcriptome and targeted analysis in single cells on BD Rhapsody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3531.
Екатерина Конопля-Стасюкова — одна из первых женщин — земских врачей на Екатеринославщине
Authors: M.P. Chaban, Z.I. Shevtsova, V.V. Gaponov
Journal: GASTROENTEROLOGY (2019)

Представлены жизненный путь и профессиональная деятельность земского врача Екатерины Конопли-Стасюковой на Екатеринославщине. Ее муж Михаил Стасюков — один из первых ветеринарных врачей Екатеринославского уезда. Их сын Николай Стасюк — член первого украинского правительства, член Центральной и Малой Рад, генеральный секретарь пищевых дел, экономист, литератор, публицист, редактор.
Multicenter phase 2 trial of weekly 5-FU plus l-LV regimen as salvage line chemotherapy for oral fluorouracil-resistant advanced gastric cancer (HGCSG1502)
Authors: A. Ueda, T. Muranaka, Y. Kawamoto, K. Sawada, H. Nakatsumi, K. Harada, Y. Kobayashi, T. Miyagishima, K. Hatanaka, M. Dazai, S. Kawahata, T. Sasaki, Y. Sasaki, S. Kato, K. Shinada, Y. Tsuji, S. Yuki, N. Sakamoto, N. Nishimoto, Y. Sakata, Y. Komatsu
Journal: Annals of Oncology (2019)
Abstract 1920: PC9 AZD9291-resistant (PC9-OSIR) cell line, a useful cell model for novel drug discovery
Authors: Zhaoshuai Bai, Guoqian Wang, Xiaolin Zhou, Zhongquan Mu, Feng Hao, Jinying Ning
Journal: Cancer Research (2019)

Abstract Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the leading cause of lung cancer-related mortality. Identification of EGFR as a driver gene of NSCLC has led to the development of EGFR inhibitors, such as Gefitinib, Erlotinib, Afatinib and Osimertinib (AZD9291). AZD9291, a third-generation EGFR inhibitor, has been approved as the first-line treatment for patients with EGFR T790M mutation-positive NSCLC. Resistance to AZD9291 was observed clinically and C797S mutation was reported to be a major mechanism for resistance to AZD9291.Our group has generated PC9 AZD9291-resistant (PC9-OSIR) cell line using a dose-escalation method after treatment of the cells with mutagenic agent. Specifically, PC9 cells was treated by AZD99291 with increasing dose for 2 weeks, and remaining live cells was retrieved and designated as PC9-OSIR. Cell survival assay showed that IC50 of PC9-OSIR was over 2μM, 100-fold more resistant than the parental PC9 cells. We explored the resistance mechanisms using whole exome sequencing (WES) and RNA-Seq, but did not find EGFR C797S mutation—the most common resistance mechanism to AZD9291—in PC9-OSIR, suggesting a likely novel resistance mechanism, possibly the activation of a bypass signaling pathway, which will be elucidated by further studies.The PC9-OSIR cell line can be a useful cell line model, in addition to cell lines with C797S mutation, in the development of future EGFR inhibitors. It can also be used to explore new mechanisms of resistance to AZD9291 resistance. Note: This abstract was not presented at the meeting. Citation Format: Zhaoshuai Bai, Guoqian Wang, Xiaolin Zhou, Zhongquan Mu, Feng Hao, Jinying Ning. PC9 AZD9291-resistant (PC9-OSIR) cell line, a useful cell model for novel drug discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1920.
Abstract 4895: Natural history and outcome of patients presenting a metastatic breast cancer with PIK3CA mutation
Authors: Fernanda Mosele, Benjamin Verret, Amelie Lusque, Thomas Filleron, Thomas Bachelot, Monica Arnedos, Mario Campone, Florence Dalenc, Claudia Lefeuvre, Marie Paule Sablin, Hervé Bonnefoi, Ludovic Lacroix, Ivan Bièche, Anthony Gonçalves, William Jacot, Marta Jimenez, Amelie Jacquet, Fabrice Andre, Fabrice Andre
Journal: Cancer Research (2019)

Abstract BACKGROUND: Activating PIK3CA mutations occur in 20-30% of patients with metastatic breast cancer (mBC). A recent study showed that alpha selective PI3K inhibitors improve outcome in patients with PIK3CA mutation, HR+/Her2- mBC. There is a need to better understand the natural history of PIK3CA mutant mBC to optimally position of this drug family. PATIENTS AND METHODS: 649 patients from SAFIR02 trial (NCT02299999), for which mutational profile was available and with clinical data entered in a database, were selected for this analysis. Associations between PIK3CA mutation, clinical characteristics and outcome were analyzed. RESULTS: 143 patients (22%) harbor PIK3CA mutation in tumor sample. 10% (n=27) and 34% (n=104) of TNBC and HR+/Her2- mBC presented a PIK3CA mutation respectively (p&amp;lt;0.001). In patients with HR+/Her2- mBC, there is no significant association between PIK3CA mutation and site of metastases or number of metastases (p&amp;lt;0.01). In the same group, patients with PIK3CA mutations were less sensitive to chemotherapy (stable disease or response: 51.3% vs. 69.2% in PIK3CA wild type; p=0.005) (Odds ratio multivariate: 0.40 [95% CI: 0.22-0.71] p=0.002). The median overall survival (OS) for patients with PIK3CA mutated HR+/Her2- mBC was of 19.6 months vs. 23.5 for patients with PIK3CA wild type (p=0.048) (HR multivariate: 1.44 [95% CI: 1.02-2.03] p=0.039). HR+/Her2- mBC with PIK3CA mutations presented more frequently a MAP3K1 mutation (16% vs. 4%, p=0.0002). In the TNBC group, the median OS in patients with PIK3CA mutated cancer was of 24.2 months vs. 14 months in the wild type group (p=0.028). CONCLUSION: Patients with PIK3CA mutated, HR+/Her2- mBC are less sensitive to chemotherapy and present a shorter survival. These data emphasize the need for new therapies in this setting, and to position these therapies earlier than chemotherapy in the treatment sequences. Citation Format: Fernanda Mosele, Benjamin Verret, Amelie Lusque, Thomas Filleron, Thomas Bachelot, Monica Arnedos, Mario Campone, Florence Dalenc, Claudia Lefeuvre, Marie Paule Sablin, Hervé Bonnefoi, Ludovic Lacroix, Ivan Bièche, Anthony Gonçalves, William Jacot, Marta Jimenez, Amelie Jacquet, Fabrice Andre, Fabrice Andre. Natural history and outcome of patients presenting a metastatic breast cancer with PIK3CA mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4895.
Splanchnic vein thrombosis in cholangiocarcinoma. A retrospective observational study. Donostia University Hospital
Authors: A. Landa, B. Sánchez, M. Diaz, M. Otaño, A. Medina, C. Fernández Catalán, A. Santos, L. Izquierdo, A. La Casta Muñoa
Journal: Annals of Oncology (2019)
Abstract 4: Discovery of novel and highly potent small molecule inhibitors of chemokine receptor CXCR4
Authors: Xiong Fang, Qian Meng, Xiao Fang, Siyu Zhu, Yazi Huang, Jing An, Yan Xu, Ziwei Huang
Journal: Cancer Research (2019)

Abstract Introduction: CXCR4 is a member of chemokine receptor and G protein coupled receptor (GPCR) families. Its interaction with the chemotactic ligand stromal cell-derived factor 1 (SDF-1 or CXCL12) plays important roles in physiological and pathological processes. Recent studies have showed that the blockade of CXCL12-CXCR4 interaction by small molecules can be used in several clinical applications, including sensitizing cancer cells to chemotherapy, mobilizing hematopoietic stem cells (HSCs) to the blood for HSC collection, and inhibiting the tumor metastasis. To date, AMD3100 (Plerixafor) is the only clinically approved drug used in combination with G-CSF for mobilizing HSCs. Here, we report the discovery and development of a new class of highly potent small molecule CXCR4 inhibitors which can strongly antagonize CXCL12-CXCR4 interaction and mobilizing HSCs. Methods: Based on the crystal structures of CXCR4 showing a major and minor subpockets, we applied a fragment-based combinatorial design (FBCD) strategy to design a new class of hybrid molecules to recognize these two subpockets. A series of designed compounds were chemically synthesized and tested in a panel of biological assays including competitive CXCR4 binding, chemotaxis, calcium mobilization and CXCR4 internalization to characterize their biological activities. Furthermore, site-directed mutagenesis coupled with molecular docking simulation was carried out to determine the binding modes of the most potent compounds. Results: More than 30 compounds were synthesized and characterized. Among them, compound HFX51116 showed the most potent CXCR4 binding activity (IC50 = 12.2 nM), which was more potent than AMD3100 tested in parallel (IC50 = 325.3 nM). Furthermore, HFX51116 displayed remarkable inhibition of calcium mobilization (IC50 = 1.478 nM) and chemotaxis activity (IC50 = 252.7 nM), both of which are better than those of AMD3100. In addition, mutational studies and molecular docking simulation suggested that HFX51116 recognizes the minor subpocket mainly and major subpocket partially. Conclusions: Our findings have demonstrated that HFX51116 is a promising novel lead compound for developing a new class of small molecule therapeutics targeting CXCR4. Citation Format: Xiong Fang, Qian Meng, Xiao Fang, Siyu Zhu, Yazi Huang, Jing An, Yan Xu, Ziwei Huang. Discovery of novel and highly potent small molecule inhibitors of chemokine receptor CXCR4 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4.
Phase II study of ABBV-399 (Process II) in patients with C-MET positive stage IV/recurrent lung squamous cell cancer (SCC): LUNG-MAP sub-study S1400K (NCT03574753).
Authors: Saiama Naheed Waqar, Mary Weber Redman, Susanne M. Arnold, Fred R. Hirsch, Philip C. Mack, Lawrence Howard Schwartz, David R. Gandara, Tom Stinchcombe, Natasha B. Leighl, Suresh S. Ramalingam, Saloni H. Tanna, Ryan S. Raddin, Katherine Minichiello, Karen Kelly, Jeffrey D. Bradley, Roy S. Herbst, Vassiliki Papadimitrakopoulou
Journal: Journal of Clinical Oncology (2019)

9075 Background: Lung-MAP is a platform trial to assess targeted therapies in SCC. S1400K was designed to evaluate the response to ABBV-399, an antibody-drug conjugate targeting C-MET, in patients with C-Met positive SCC. Methods: Patients with previously treated SCC with c-MET positive tumors (H score ≥150, Ventana SP44 assay), PS≤1, adequate organ function, peripheral neuropathy ≤ grade (G) 2, edema ≤ G2, albumin ≥3 g/dL, hepatic involvement by tumor &lt; 50%. Patients were enrolled into 2 cohorts: Cohort 1 (immune checkpoint inhibitor (ICI) naïve) and cohort 2 (ICI refractory). ABBV-399 2.7 mg/kg was administered intravenously over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. Response assessments were performed every 6 weeks. The primary endpoint was response by RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), response within cohort, duration of response (DoR), and toxicities associated with ABBV-399. Interim analysis was planned after 20 evaluable patients, with ≥ 3 responses needed to continue enrollment. Results: Between 2/15/18 and 10/16/2018, 50 patients (17% of patients screened) were assigned to S1400K, 28 patients enrolled (15 in cohort 1 and 13 in cohort 2), 25 were determined eligible, of whom 23 received ABBV-399 and were assessed for adverse events. There were 3 G5 events (2 pneumonitis, both in cohort 2 and 1 bronchopulmonary hemorrhage) and 4 G3 events. S1400K was temporarily closed on 10/16/2018 for interim analysis and safety concerns, and formally closed on 12/21/2018. Two responses were reported, both in cohort 1 (1 complete and 1 unconfirmed partial response, CR and UPR) for a response rate of 9% (95% CI: 0-20%). The CR remains on treatment at 4 months and DoR for the UPR was 2.3 months. Ten patients had stable disease and disease control rate was 52% (3-73%). The median OS and PFS were 4.7 and 2.4 months. Conclusions: ABBV-399 failed to meet the pre-specified response needed to justify continuing enrollment. Pneumonitis was an unanticipated toxicity observed in patients with SCC with previous immunotherapy exposure. Clinical trial information: NCT03574753.
Abstract 14644: Phenotype-assisted Interpretation of Variants in Genes Causal for Familial Hypercholesterolemia
Authors: Xiao Fan, Mayya S Safarova, Keyue Ding, Iftikhar J Kullo
Journal: Circulation (2017)

Background: Assigning pathogenicity to putatively functional variants identified by next generation sequencing is a major challenge for genomic medicine. We aimed to improve the accuracy of assigni...
Abstract 914: Development of a whole-urine, next-generation sequencing-based assay for early detection of aggressive prostate cancer
Authors: Andi K. Cani, Kevin Hu, Javed Siddiqui, Sumin Han, Daniel H. Hovelson, Chia-Jen Liu, Simpa S. Salami, Ganesh S. Palapattu, Todd M. Morgan, John T. Wei, Arul M. Chinnaiyan, Scott A. Tomlins
Journal: Cancer Research (2019)

Abstract Despite advances in biomarker development, early detection of aggressive prostate cancer (PCa) remains challenging. Existing biomarkers show modest improvement over models based on serum prostate specific antigen (PSA). We have previously developed a clinical-grade laboratory-developed test, named MiProstate Score (MiPS), for individualized risk prediction of aggressive prostate cancer. It uses transcription-mediated amplification to quantify the gene-fusion TMPRSS2:ERG (T2:ERG) (T1E4 splice isoform) and the lncRNA PCA3 from whole-urine obtained after a digital rectal exam (DRE), combined with serum PSA. To improve MiPS, we describe here the pre-clinical development and validation of a targeted next generation sequencing assay (NGS-MiPS) using post-DRE urine RNA to asses ~90 PCa transcriptomic biomarkers. These include those in MiPS as well as many isoforms of common PCa gene fusions, mRNA, and lncRNA candidate biomarkers nominated by our large-scale PCa tissue RNAseq and other sources. We have obtained a 98% informative sample rate from 2.5 mL of urine and high technical reproducibility (Pearson r=0.99). Risk scores for having PCa [or high-grade PCa (Gleason Score &amp;gt;6)] on biopsy, as determined by clinical MiPS vs. the clinical MiPS model using NGS data, were highly concordant, Pearson’s r=0.74 (and r=0.81). Urine from patients with benign or Gleason 6 vs. Gleason ≥ 4+3=7 cancer on biopsy (extreme design) showed expected differences in the levels of T2:ERG T1E4 (p=0.00003) and PCA3 (p=0.07), with additional T2:ERG splice isoforms and other biomarkers also being significantly different between low vs. high grade cancer. Feature selection and logistic regression trained in an extreme design cohort (n=73) yielded a 29-transcript model that outperformed MiPS and serum PSA in two validation cohorts: 1. A held-out set from the extreme design cohort n=36, AUC 0.81 vs. 0.76 and 0.63 respectively; 2. A separate active surveillance cohort n=45, AUCs 0.66 vs. 0.56 and 0.53 respectively. These results support the potential utility of our urine based targeted NGS assay to supplement serum PSA for the early detection of aggressive prostate cancer. Citation Format: Andi K. Cani, Kevin Hu, Javed Siddiqui, Sumin Han, Daniel H. Hovelson, Chia-Jen Liu, Simpa S. Salami, Ganesh S. Palapattu, Todd M. Morgan, John T. Wei, Arul M. Chinnaiyan, Scott A. Tomlins. Development of a whole-urine, next-generation sequencing-based assay for early detection of aggressive prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 914.