Digital Commons Network^™

The Clinical Utility Of A Next-Generation Sequencing-Based Approach To Detecting Circulating Hpv Dna In Patients With Advanced Anal Cancer, Deepak Bhamidipati, Jay R Johnson, Kangyu Lin, Helene Pelicano, Cathy Eng, Ryan Huey, Robert A Wolff, Daniel M Halperin, Michael F Frumovitz, Ignacio I Wistuba, Dzifa Y Duose, Saradhi Mallampati, Rajyalakshmi Luthra, Van K Morris

Faculty, Staff and Student Publications

Background: To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA).

Methods: ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4 Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types. The HPV type, copy number (CN), and integration sites were determined using a bioinformatic pipeline.

Results: A total of 77 plasma samples from 28 patients with …

Computational Investigation Of The Unveils Nsd2 Inhibition Potential Of Berberis Vulgaris, Sambucus Nigra, And Morus Alba Through Virtual Screening, Molecular Docking, Md Simulation, And Dft Analyses, Supriyo Saha, Vanshita Gupta, Ahad Hossain, Prinsa Prinsa, Jannatul Ferdous, Kiran Bharat Lokhande, Vikash Jakhmola, Sarkar M. A. Kawsar

Karbala International Journal of Modern Science

Nuclear receptor binding set domain protein 2 (NSD2) plays a key role in chromatin regulation and is associated with different cancers and other developmental problems. Berries are rich in major secondary metabolites with anticancer properties. Here, we virtually screened 145 berry phytochemicals as putative NSD2 inhibitors via structure-based virtual screening, molecular docking, MD simulations, and DFT and ADMET analyses. Among them, α-carotene had the maximum docking score of -9.9 kcal/mol, followed by sulfuretin and β-amyrin. MD simulation analysis revealed that the dynamic behavior of the ligand‒NSD2 complexes was within the limit, indicating no significant changes in the structural integrity of …

Antimicrobial Effect Of Herbs Extracted With Ethanol Compared To Ampicillin, Brianna Neilan, Laura Rowe

Posters-at-the-Capitol

Antibiotics are commonly used to treat bacterial infections within the medical field, however there are growing concerns of antibiotic resistance. Before the introduction of antibiotics herbs were commonly used to treat infections, and herbal medicine is still used in many communities and cultures. Bacteria’s increasing resistance to traditional antibiotics has caused herbal medicines to become a significant research topic recently. Methods of herbal medicine preparation include preparing teas using hot water, and tinctures that soak herbs in alcohol for several weeks. Previous research has shown significant antimicrobial effects of some herbs when soaked in water and other liquids. The aim …

Research Progress And Clinical Translation Potential Of Coronary Atherosclerosis Diagnostic Markers From A Genomic Perspective, Hanxiang Liu, Yuchen Zhang, Yueyan Zhao, Yuzhen Li, Xiaofeng Zhang, Lingyu Bao, Rongkai Yan, Yixin Yang, Huixian Zhou, Jinming Zhang, Siyuan Song

Children’s Nutrition Research Center Staff Publications

Objective: Coronary atherosclerosis (CAD) is characterized by arterial intima lipid deposition, chronic inflammation, and fibrous tissue proliferation, leading to arterial wall thickening and lumen narrowing. As the primary cause of coronary heart disease and acute coronary syndrome, CAD significantly impacts global health. Recent genetic studies have demonstrated CAD's polygenic and multifactorial nature, providing molecular insights for early diagnosis and risk assessment. This review analyzes recent advances in CAD-related genetic markers and evaluates their diagnostic potential, focusing on their applications in diagnosis and risk stratification within precision medicine.

Methods: We conducted a systematic review of CAD genomic studies from PubMed and …

What’S New In Esophageal Atresia Treatment?, Alexandra N. Jimenez Gonzalez

Mako: NSU Undergraduate Student Journal

No abstract provided.

Retracted: Conserved Domains In Promoters Of Differentially Expressed Genes: How To Find Them And What Can They Tell Us?, Emalynn E. Tobias

Mako: NSU Undergraduate Student Journal

THIS ARTICLE HAS BEEN RETRACTED DUE TO THE FOLLOWING REASON: inadvertent errors in several citations.

The complex process of regulating gene expression involves a large number of cis- and trans-acting components. The cis elements also referred to as cis regulatory elements (CREs) are highly conserved across species, and are often referred to as conserved domains mainly located in the promoters of genes. The trans acting sequences such as enhancers, moderators and insulators are also crucial in the regulation of gene expression. With an increased influx of genomic and transcriptomic data, study of differentially expressed genes (DEGs) is highly effective in …

How Did Covid-19 Impact Physiology Research Globally? – Lessons Learned And Future Recommendations, Jeet Patel, Santanu De

Mako: NSU Undergraduate Student Journal

The Coronavirus Infectious Disease 2019 (COVID-19) pandemic caused massive changes in the medical field across the globe. As the whole world moved from in-person to remote activities, students found themselves in a predicament where they were compelled towards schooling and work online from home. This would mean that all projects, research, tests, and meetings were conducted over Zoom or other online meeting platforms. Laboratories were shut down or only a limited number of people were allowed to enter to conduct the necessary research. This paper discusses how the COVID-19 pandemic affected research process and experiments within various aspects of the …

Discerning The Role Of Microtubule Acetylation During Hiv-1 Infection, Drew Michael Lichon

Dissertations

The host-pathogen interactions underlying Human Immunodeficiency Virus type 1 (HIV-1) infection are complex and involve the exploitation of host cellular machinery. This thesis investigates the roles of dynein adaptors, microtubule acetylation, and TRIM69-mediated restriction in HIV-1 infection. Through a series of detailed experiments, we explore how HIV-1 utilizes multiple dynein adaptors, such as BICDR1 and Hook3, for intracellular transport, and reveal that these adaptors are critical for efficient viral trafficking. Conversely, the knockdown of Ninein surprisingly enhances HIV-1 infectivity, suggesting a nuanced regulatory role for this adaptor in viral transport. Further, this thesis challenges the prevailing paradigm that microtubule acetylation …

Investigating The Role Of The Nsp15 Amino-Terminal Domain In Nsp15 Function, Viral Replication, And Pathogenesis, Monika Evdokimova

Dissertations

Identifying conserved mechanisms used by viruses to delay host innate responses can reveal potential targets for antiviral therapeutics. Here, we investigated coronavirus nonstructural protein 15 (nsp15), which encodes a highly conserved endoribonuclease (EndoU). EndoU functions as an immune antagonist by limiting the accumulation of viral replication intermediates that would otherwise be sensed by the host. Despite being a promising antiviral target, it has been difficult to develop small molecule inhibitors that target the EndoU active site. We generated nsp15 mutants of SARS-CoV-2 and mouse coronavirus MHV-A59 and identified conserved residues within the amino-terminal domain that are required for EndoU activity. …

Light-Dark Shift Promotes Colon Carcinogenesis Through Accelerated Colon Aging, Deepak Sharma, Phillip A Engen, Abu Osman, Darbaz Adnan, Maliha Shaikh, Mostafa K Abdel-Reheem, Ankur Naqib, Stefan J Green, Bruce Hamaker, Christopher B Forsyth, Lin Cheng, Ali Keshavarzian, Khashayarsha Khazaie, Faraz Bishehsari

Faculty, Staff and Student Publications

Colorectal cancer (CRC) is the third most common cancer worldwide, with rising prevalence among younger adults. Several lifestyle factors, particularly disruptions in circadian rhythms by light-dark (LD) shifts, are known to increase CRC risk. Epidemiological studies previously showed LD-shifts are associated with increased risk of CRC. To explore the mechanisms and interactions between LD-shift and intestinal aging, we investigated how the combination of LD-shifts and aging impacts colon carcinogenesis development. Our data showed that LD-shifts and aging increased colon tumorigenesis. Notably, LD-shift accelerated intestinal aging by altering aging-related pathways, such as intestinal barrier damage, accompanied by dysbiotic changes in the …

Utilizing Patient-Derived Xenografts To Model Precision Oncology For Biliary Tract Cancer, Timothy P Diperi, Kurt W Evans, Stephen Scott, Xiaofeng Zheng, Kaushik Varadarajan, Lawrence N Kwong, Michael Kahle, Hop S Tran Cao, Ching-Wei Tzeng, Thuy Vu, Sunhee Kim, Fei Su, Maria Gabriela Raso, Yasmeen Rizvi, Ming Zhao, Huamin Wang, Sunyoung S Lee, Timothy A Yap, Jordi Rodon, Milind Javle, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Purpose: Biliary tract cancers, which are rare and aggressive malignancies, are rich in clinically actionable molecular alterations. A major challenge in the field is the paucity of clinically relevant biliary tract cancer models that recapitulate the diverse molecular profiles of these tumors. The purpose of this study was to curate a collection of patient-derived xenograft (PDX) models that reflect the spectrum of genomic alterations present in biliary tract cancers to create a resource for modeling precision oncology.

Experimental design: PDXs were derived from biliary tract cancer samples collected from surgical resections or metastatic biopsies. Alterations present in the PDXs were …

Revisiting Phosphoregulation Of Cdc25c During M-Phase Induction, Tan Tan, Chuanfen Wu, Ruoning Wang, Bih-Fang Pan, David Hawke, Fumin Yin, Zehao Su, Boye Liu, Sue-Hwa Lin, Wei Zhang, Jian Kuang

Faculty, Staff and Student Publications

Cdc25C undergoes a sudden and substantial gel mobility shift at M-phase onset, correlating with abrupt activation of both Cdc25C and Cdk1 activities. A positive feedback loop between Cdk1 and Cdc25C has been used to explain this hallmark phenomenon. Here, we demonstrate that the M-phase supershift and robust activation of Cdc25C are due to the site-comprehensive phosphorylation of its long intrinsically disordered regulatory domain without requiring Cdk1 or other major mitotic kinase activities. The phosphorylation process involves substrate-mediated assembly of phosphorylation machinery that catalyzes multisite phosphorylation continuously without substrate dissociation. In contrast to the site-comprehensive phosphorylation of Cdc25C occurring at M-phase …

Clinical And Molecular Characteristics Of Patients With Brain Metastasis Secondary To Pancreatic Ductal Adenocarcinoma, Mahmoud Yousef, Mark W Hurd, Abdelrahman Yousef, Ethan B Ludmir, Ashwathy B Pillai, Jennifer Peterson, Eugene J Koay, Sali Albarouki, Ching-Wei Tzeng, Rebecca Snyder, Matthew H G Katz, Huamin Wang, Michael J Overman, Anirban Maitra, Shubham Pant, Brandon G Smaglo, Robert A Wolff, James Yao, John P Shen, Dan Zhao

Faculty, Staff and Student Publications

Background: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Secondary brain metastasis (Br-M) occurs in less than 1% of patients. Clinical characteristics and molecular alterations have not been characterized in this rare patients' subset.

Materials and methods: The Foundry software platform was used to retrospectively query electronic health records for patients with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and overall survival (OS) data were analyzed.

Results: Br-M was diagnosed in 44 patients with PDAC. Median follow-up was 78 months; median OS from initial PDAC diagnosis was 47 months. Median duration from PDAC diagnosis …

Exosomal Galectin-3 Promotes Peritoneal Metastases In Gastric Adenocarcinoma Via Microenvironment Alterations, Yibo Fan, Shumei Song, Melissa Pool Pizzi, Gengyi Zou, Jody V Vykoukal, Katsuhiro Yoshimura, Jiankang Jin, George A Calin, Rebecca E Waters, Qiong Gan, Linghua Wang, Samir Hanash, Shilpa S Dhar, Jaffer A Ajani

Faculty, Staff and Student Publications

Peritoneal carcinomatosis (PC) in gastric adenocarcinoma (GAC) is the most common metastatic site and leads to a short median survival. Exosomes have been shown to remodel the microenvironment, facilitating tumor metastases. However, the functional component in GAC cell-derived exosomes that remodel the landscape in the peritoneal cavity remains unclear. To address this, we performed in-depth proteomic profiling of ascites-derived exosomes from patients with PC, and we found that Galectin-3 was highly enriched in exosomes derived from malignant ascites. exosomal Galectin-3 was the crucial regulator of PC. Blockage of exosomal Galectin-3 significantly inhibited tumor metastases and prolonged overall survival. Exosomal Galectin-3 …

Dysregulated Klf4 Expression Plays A Pivotal Role In The Pathogenesis Of Pancreatic Intraductal Papillary Mucinous Neoplasms, Xiangsheng Zuo, Liang Wang, Yi Liu, Huamin Wang, Margarete Hafley, Mihai Gagea, Ru Chen, Yun Xiong, Sheng Pan, Imad Shureiqi, Robert S Bresalier, Daoyan Wei

Faculty, Staff and Student Publications

No abstract provided.

Mission Success: Mastering Muscle Function Through Humanoid Analysis, Amber M. Chelette

Educational Practices in Kinesiology

Knowledge of muscle function and human movement are essential skills of all kinesiology students. In the humanoid activity, teams are challenged to determine whether a muscle is essential to the successful development of a humanoid being sent to Mars. This activity provides a significant learning experience regarding muscle anatomy, function, and movement analysis. The humanoid activity is intended for use in a face-to-face upper-level kinesiology anatomy or movement analysis course and best implemented with class sizes of 20-30 students. The total time commitment is approximately 45 minutes.

Halogeton And Greasewood Poisoning In Cattle And Sheep In Utah, E. Jane Kelly, Stephen T. Lee, Ammon Brown, Daniel Cook

Poisonous Plant Research (PPR)

Halogeton (Halogeton glomeratus) is a fast-growing annual plant while greasewood (Sarcobatus vermiculatus) is a perennial shrub of the Western States. Oxalates are the toxic principle in halogeton and greasewood. Most losses occur when hungry animals are allowed to graze in heavy stands of halogeton and greasewood. Halogeton and greasewood are always dangerous and become more toxic as the growing season progresses. Here we report on two clinical cases of halogeton and greasewood poisoning in cattle and sheep. Histologically, oxalate crystals were observed in the kidneys of the cow and sheep consistent with oxalate poisoning. Oxalate was …

Refurbishing Used Gps Transmitters Improves Performance For Subsequent Deployments On Greater Sage-Grouse, Melissa S. Chelak, Michel T. Kohl, Justin R. Small, Kurt T. Smith, Aaron C. Pratt, Jeffrey L. Beck, Codi R. Backen, M. Brandon Flack, Hailey P. Wayment, Jason A. Wood, Ryan Howell, Trevon D. Strange, Lucian R. Mcdonald, Kezia R. Manlove, Shandra N. Frey, Randy T. Larsen, Brian A. Maxfield, David K. Dahlgren, Terry A. Messmer, David C. Stoner

Wildland Resources Student Research

Global Positioning Systems (GPS) radio transmitters are increasingly used across taxa to monitor animal populations. However, GPS transmitters can be susceptible to malfunctions that may result in location errors or data loss causing potential inferential bias that can have important implications for monitored species. Research using GPS transmitters on greater sage-grouse (Centrocercus urophasianus; sage-grouse) has increased, but few sage-grouse studies have evaluated GPS performance. Because sage-grouse management has been subject to intense legal and political scrutiny with consequential economic implications, reliable data acquisition is central to informed decision-making for the species. We evaluated differences in the performance of …

Hiv Associated Epigenetic Trends And Chronic Diseases: Insights Into The Hidden Burden Of Chronic Infection, Courtney G. Wallace, Zachary Capriotti, Zachary Klase

Kimmel Cancer Center Faculty Papers

Human Immunodeficiency Virus (HIV) remains a major health challenge despite dramatic advances in treatment and prevention. People living with HIV (PLWH) continue to experience high rates of non-AIDS comorbidities, including cardiovascular, renal, pulmonary, oncologic, and neurocognitive disorders. These conditions persist under viral suppression, underscoring the lasting biological impact of infection. Epigenetic dysregulation has emerged as a key driver of these outcomes. HIV integration, viral proteins, chronic inflammation, and ART exposure have all been reported to alter DNA methylation, histone modifications, transcription factor networks, and noncoding RNA regulation. These changes extend beyond infected cells, reprogramming uninfected immune and tissue compartments. Long-lived …

Exploring The Pathogen Profiles Of Ancient Feces, Drew Capone, David Holcomb, Amanda Lai, Karl Reinhard, Joe Brown

Karl Reinhard Publications

Analysis of ancient desiccated feces – termed paleofeces or coprolites – can unlock insights into the lives of ancient people. We collected desiccated feces from caves in the Rio Zape Valley in Mexico (725-920 CE). First, we extracted DNA with methods previously optimized for paleofeces. Then, we applied highly sensitive modern molecular tools (i.e., PCR pre-amplification followed by multi-parallel qPCR) to assess the presence of 30 enteric pathogens. We detected ≥1 pathogen associated gene in each of the ten samples and a mean of 3.9 pathogens per sample. The targets detected included Blastocystis spp. (n=7), atypical enteropathogenic E. coli (n=7), …

Tropical Fruit-Derived Lactiplantibacillus As Potential Probiotic And Antifungal Agents Against Fusarium Oxysporum, R. Vasundaradevi, M. Sarvajith, S. Divyashree, N. Deepa, M. Y. Sreenivasa, Premila Achar

Faculty Articles

Fifty-five lactic acid bacteria (LAB) were isolated from seven selected tropical fruits, with Solanum nigrum exhibiting the highest LAB prevalence and Couroupita guianenis and Musa fruits showing the lowest counts. Two strains isolated from Ficus racemosa demonstrated significant antifungal activity against Fusarium oxysporum. 16S rDNA sequencing identified these strains as Lactiplantibacillus plantarum MYSVCF3 and Lpb. argentoratensis MYSVCF5. The isolates displayed adaptability to a broad range of environmental conditions, including temperatures of 10–45 °C, pH 2–6, and salt up to 7%. The strains tolerated simulated gastrointestinal conditions of acid (pH-2), phenol (0.6%), and bile (0.3%) suggesting potential probiotic attributes. Lpb. …

Post-Transcriptional And Post-Translational Regulation Of Anthocyanin Biosynthesis In Sweetpotato By Ib-Mir2111 And Ibkfb: Implications For Health Promotion, Ruimin Tang, Cailiang Zhao, Jingjian Dong, Xiayu Liu, Lu Chang, Jianghui Li, Haitao Dong, Yuntao Lv, Zhuang Luo, Meiling Wu, Shan Shen, Qianwen Shan, Yuan Li, Qijun Chen, Runzhi Li, Liheng He, Qinghe Cao, Guiliang Tang, Xiaoyun Jia

Michigan Tech Publications

Introduction: Sweet potato (Ipomoea batatas (L.) Lam.) is a genetically intricate hexaploid crop. The purple-fleshed variety, enriched with anthocyanin pigments, is an outstanding source for creating high-value functional products. Previous research on anthocyanin biosynthesis has primarily focused on the above-ground plant parts at the transcriptional level. However, the regulatory mechanisms underlying anthocyanin accumulation in underground tuberous roots of sweet potato remain largely unexplored. Objectives: This study aimed to elucidate the post-transcriptional and post-translational mechanisms of Ib-miR2111 and its target gene IbKFB in anthocyanin synthesis in sweet potato. Methods: Genetic manipulation techniques were used to validate the function of Ib-miR2111 and …

Protein Translation Rates Are Negatively Correlated With Lifespan In Inbred Drosophila Strains, Harper S Kim, Madison M Hardiman, Andrew M Pickering

Faculty, Staff and Student Publications

No abstract provided.

Mitochondrial A3 Adenosine Receptor As A Mechanism For The Protective Effects Of A3ar Agonists On Chemotherapy-Induced Neuropathic Pain, Timothy M. Doyle, Kali Janes, Wen Hua Xiao, Grant R. Kolar, Hans F. Luecke, Michael Anne Gratton, Dilip K. Tosh, Kenneth A. Jacobson, Gary J. Bennett, Daniela Salvemini

Biological Sciences Faculty Research & Creative Works

Alterations in mitochondrial function are the linchpin in numerous disease states including in the development of chemotherapy-induced neuropathic pain (CIPN), a major dose-limiting toxicity of widely used chemotherapeutic cytotoxins. In CIPN, mitochondrial dysfunction is characterized by deficits in mitochondrial bioenergetics (e.g., decreased ATP production) that are thought to drive the degeneration of the peripheral nerve sensory axon terminal sensory arbors in the skin (the intraepidermal nerve fibers; IENFs) and induce abnormal spontaneous discharge in peripheral nerve sensory axons. Preserving mitochondrial function is anticipated to prevent CIPN. We have now discovered that the G-protein-coupled receptor, A3 adenosine receptor subtype (A3AR), is …

Associations Between Social Determinants Of Health And Mental Health Disorders Among U.S. Population: A Cross-Sectional Study, S. Tanarsuwongkul

Faculty Publications

Aims

The impact of social determinants of health (SDOH) on mental health is increasingly realized. A comprehensive study examining the associations of SDOH with mental health disorders has yet to be accomplished. This study evaluated the associations between five domains of SDOH and the SDOH summary score and mental health disorders in the United States.

Methods

We analyzed data from a diverse group of participants enrolled in the All of Us research programme, a research programme to gather data from one million people living in the United States, in a cross-sectional design. The primary exposure was SDOH based on Healthy …

Career: The Behavioral, Hormonal, And Neural Basis Of Coyote Monogamy, Sara M. Freeman

Funded Research Records

No abstract provided.

Electrostatic Force-Enabled Microneedle Patches That Exploit Photoredox Catalysis For Transdermal Phototherapy, Hang Zhang, Wen-Chuan Xie, Yuhang Yao, Zi-Yi Tang, Wen-Xiu Ni, Bingwu Wang, Song Gao, Jonathan L Sessler, Jun-Long Zhang

Faculty, Staff and Student Publications

Microneedle patches for topical administration of photodynamic therapy (PDT) sensitizers are attractive owing to their safety, selectivity, and noninvasiveness. However, low-efficiency photosensitizer delivery coupled with the limitations of the hypoxic tumor microenvironment remains challenging. To overcome these issues, we developed an effective microneedle patch based on intermolecular electrostatic interactions within a photosensitizer matrix containing a zinc-containing porphyrin analogue, ZnBP (w). This design improved the mechanical strength of the microneedle patch and enhanced the photosensitizer loading efficiency in aqueous environments. A key feature of the system is efficient electron transfer between ZnBP (w) and NADH upon photoirradiation. Electrostatic interactions between ZnBP …

A Case For Broadening Our View Of Mechanism In Developmental Biology, B Duygu Özpolat, Swathi Arur, Mansi Srivastava

Faculty, Staff and Student Publications

Developmental biologists can perform studies that describe a phenomenon (descriptive work) and/or explain how the phenomenon works (mechanistic work). There is a prevalent perception that molecular/genetic explanations achieved via perturbations of gene function are the primary means of advancing mechanistic knowledge. We believe this to be a limited perspective, one that does not effectively represent the breadth of work in our field. We surveyed a representative and diverse group of colleagues to share their views on what it takes to infer mechanism. Here, we briefly examine the factors that have shaped the dominant view of mechanism, summarize responses to the …

Investigating Student Noticing Of Quantitative Reasoning In Introductory Biology Labs, Jeremy L. Hsu, Sara Gartland, Joelle Prate, Charles Hohensee

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Quantitative reasoning (QR) is a key skill for undergraduate biology education. Despite this, many students struggle with QR. Here, we use the theoretical framework of student noticing to investigate why some students struggle with QR in introductory biology labs. Under this framework, what students notice when given new information and data influences how they process this information and connect it with other events to form new conceptions. Students must mentally isolate given features, create mental records of those features, and identify features or objects that they connect to existing knowledge. Identifying these features or objects is thus critical since they …

Spatial Distribution Of Tumor Cells In Clear Cell Renal Cell Carcinoma Is Associated With Metastasis And A Matrisome Gene Expression Signature, Prahlad Bhat, Pheroze Tamboli, Kanishka Sircar, Kasthuri Kannan

Faculty, Staff and Student Publications

Background/Objectives: Predicting the behavior of clear cell renal cell carcinoma (ccRCC) is challenging using standard-of-care histopathologic examination. Indeed, pathologic RCC tumor grading, based on nuclear morphology, performs poorly in predicting outcomes of patients with International Society of Urological Pathology/World Health Organization grade 2 and 3 tumors, which account for most ccRCCs.

Methods: We applied spatial point process modeling of H&E-stained images of patients with grade 2 and grade 3 ccRCCs (n = 72) to find optimum separation into two groups.

Results: One group was associated with greater spatial randomness and clinical metastasis (p < 0.01). Notably, spatial analysis outperformed standard pathologic grading in predicting clinical metastasis. Moreover, cell-to-cell interaction distances in the metastasis-associated group were significantly greater than those in the other patient group and were also greater than expected by the random distribution of cells. Differential gene expression between the two spatially defined groups of patients revealed a matrisome signature, consistent with the extracellular matrix's crucial role in tumor invasion. The top differentially expressed genes (with a fold change > 3) stratified a larger, multi-institutional …