Medicine and Health Sciences Commons^™

Identification Of Ct-Based Non-Invasive Radiomic Biomarkers For Overall Survival Prediction In Oral Cavity Squamous Cell Carcinoma, Xiao Ling, Gregory S. Alexander, Jason Molitoris, Jinhyuk Choi, Lisa Schumaker, Ranee Mehra, Daria A. Gaykalova, Lei Ren

Department of Radiation Oncology Faculty Papers

This study addresses the limited non-invasive tools for Oral Cavity Squamous Cell Carcinoma (OSCC) survival prediction by identifying Computed Tomography (CT)-based biomarkers to improve prognosis prediction. A retrospective analysis was conducted on data from 149 OSCC patients, including CT radiomics and clinical information. An ensemble approach involving correlation analysis, score screening, and the Sparse-L1 algorithm was used to select functional features, which were then used to build Cox Proportional Hazards models (CPH). Our CPH achieved a 0.70 concordance index in testing. The model identified two CT-based radiomics features, Gradient-Neighboring-Gray-Tone-Difference-Matrix-Strength (GNS) and normalized-Wavelet-LLL-Gray-Level-Dependence-Matrix-Large-Dependence-High-Gray-Level-Emphasis (HLE), as well as stage and alcohol usage, …

Novel Urine Cell-Free Dna Methylation Markers For Hepatocellular Carcinoma, Selena Lin, Wei Xia, Amy Kim, Dion Chen, Shelby Schleyer, Lin Choi, Zhili Wang, James Hamilton, Harry Luu, Hie-Won Hann, Ting-Tsung Chang, Chi-Tan Hu, Abashai Woodard, Terence Gade, Ying-Hsiu Su

Division of Gastroenterology and Hepatology Faculty Papers

An optimized hepatocellular carcinoma (HCC)-targeted methylation next generation sequencing assay was developed to discover HCC-associated methylation markers directly from urine for HCC screening. Urine cell-free DNA (ucfDNA) isolated from a discovery cohort of 31 non-HCC and 30 HCC was used for biomarker discovery, identifying 29 genes with differentially methylated regions (DMRs). Methylation-specific qPCR (MSqPCR) assays were developed to verify the selected DMRs corresponding to 8 genes (GRASP, CCND2, HOXA9, BMP4, VIM, EMX1, SFRP1, and ECE). Using archived ucfDNA, methylation of GRASP, HOXA9, BMP4, and ECE1, were found to be significantly different (p < 0.05) between HCC and non-HCC patients. The four markers together with previously reported GSTP1 and RASSF1A markers were assessed as a 6-marker panel in an independent training cohort of 87 non-HCC and 78 HCC using logistic regression modeling. AUROC of 0.908 (95% CI, 0.8656-0.9252) was identified for the 6-marker panel with AFP, which was significantly higher than AFP-alone (AUROC 0.841 (95% CI, 0.778-0.904), p = 0.0026). Applying backward selection method, a 4-marker panel was found to exhibit similar performance to the 6-marker panel with AFP having 80% sensitivity compared to 29.5% by AFP-alone at a specificity of 85%. This study supports the potential use of methylated transrenal ucfDNA for HCC screening.

Current Relevance Of Biomarkers In Diagnosis Of Periprosthetic Joint Infection: An Update., Saksham Tripathi, Saad Tarabichi, Javad Parvizi, Ashok Rajgopal

Rothman Institute Faculty Papers

With a significant rise in the number of arthroplasty procedures performed worldwide, the increasing revision burden posed by periprosthetic joint infection (PJI) is a matter of growing concern. In spite of various attempts to diagnose PJI, there are no defined tests that can be called a gold standard. Given the importance of early diagnosis in PJI, newer tests and biomarkers have been introduced to improve cumulative diagnostic accuracy. Novel biomarkers like calprotectin, lipocalcin, monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and platelet-to-mean platelet volume ratio have demonstrated a potential as diagnostic biomarkers for PJI. This article discusses the relevance of available …

Selection Of Optimal Quantile Protein Biomarkers Based On Cell-Level Immunohistochemistry Data, Misung Yi, Tingting Zhan, Amy R. Peck, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, Hai Hu, Yunguang Sun, Hallgeir Rui, Inna Chervoneva

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: Protein biomarkers of cancer progression and response to therapy are increasingly important for improving personalized medicine. Advanced quantitative pathology platforms enable measurement of protein expression in tissues at the single-cell level. However, this rich quantitative cell-by-cell biomarker information is most often not exploited. Instead, it is reduced to a single mean across the cells of interest or converted into a simple proportion of binary biomarker-positive or -negative cells.

RESULTS: We investigated the utility of retaining all quantitative information at the single-cell level by considering the values of the quantile function (inverse of the cumulative distribution function) estimated from a …

Development Of A Biomarker Panel For Assessing Cardiovascular Risk In Diabetic Patients With Chronic Limb-Threatening Ischemia (Clti): A Prospective Study, Elisabetta Nardella, Federico Biscetti, Maria Margherita Rando, Andrea Leonardo Cecchini, Maria Anna Nicolazzi, Enrica Rossini, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Medicine Faculty Papers

BACKGROUND: Lower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), …

Mechanisms Of Chromosomal Instability (Cin) Tolerance In Aggressive Tumors: Surviving The Genomic Chaos, Brittiny Dhital, Veronica Rodriguez-Bravo

Student Papers, Posters & Projects

Chromosomal instability (CIN) is a pervasive feature of human cancers involved in tumor initiation and progression and which is found elevated in metastatic stages. CIN can provide survival and adaptation advantages to human cancers. However, too much of a good thing may come at a high cost for tumor cells as excessive degree of CIN-induced chromosomal aberrations can be detrimental for cancer cell survival and proliferation. Thus, aggressive tumors adapt to cope with ongoing CIN and most likely develop unique susceptibilities that can be their Achilles' heel. Determining the differences between the tumor-promoting and tumor-suppressing effects of CIN at the …

Nationwide Results Of Microorganism Antigen Testing As A Component Of Preoperative Synovial Fluid Analysis., Krista O'Shaughnessey Toler, Pearl Ravindra Paranjape, Alex Mclaren, Brett Levine, Alvin Ong, Carl Deirmengian

Rothman Institute Faculty Papers

BACKGROUND: Antigen immunoassays to detect synovial fluid (SF) microorganisms have recently been made available for clinical use. The purpose of this study was to determine the sensitivity and specificity of an SF microorganism antigen immunoassay detection (MID) panel, evaluate the panel's capability to detect microorganisms in the setting of culture-negative periprosthetic joint infection (PJI), and determine diagnostic predictive values of the MID panel for PJI.

METHODS: This study included 67,441 SF samples obtained from a hip or knee arthroplasty, from 2,365 institutions across the United States, submitted to 1 laboratory for diagnostic testing. All data were prospectively compiled and then …

Rational Targets Of Therapy In Extranodal Nk/T-Cell Lymphoma, Ajay Major, Pierluigi Porcu, Bradley M Haverkos

Department of Medical Oncology Faculty Papers

Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive extranodal non-Hodgkin lymphoma (NHL) with poor outcomes, particularly in advanced-stage and relapsed/refractory disease. Emerging research on molecular drivers of ENKTL lymphomagenesis by next-generation and whole genome sequencing has revealed diverse genomic mutations in multiple signaling pathways, with the identification of multiple putative targets for novel therapeutic agents. In this review, we summarize the biological underpinnings of newly-understood therapeutic targets in ENKTL with a focus on translational implications, including epigenetic and histone regulatory aberrations, activation of cell proliferation signaling pathways, suppression of apoptosis and tumor suppressor genes, changes in the tumor microenvironment, and EBV-mediated …

Sakurabonsai: Protocol Design Of A Novel, Prospective Study To Explore Clinical, Imaging, And Biomarker Outcomes In Patients With Aqp4-Igg-Seropositive Neuromyelitis Optica Spectrum Disorder Receiving Open-Label Satralizumab, Jeffrey L Bennett, Kazuo Fujihara, Ho Jin Kim, Romain Marignier, Kevin C O'Connor, Robert C Sergott, Anthony Traboulsee, Heinz Wiendl, Jens Wuerfel, Scott S Zamvil, Veronica G Anania, Regine Buffels, Thomas Künzel, Annemarie N Lekkerkerker, Siân Lennon-Chrimes, Sean J Pittock

Wills Eye Hospital Papers

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that produces acute, unpredictable relapses causing cumulative neurological disability. Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced NMOSD relapse risk vs. placebo in two Phase 3 trials: SAkuraSky (satralizumab ± immunosuppressive therapy; NCT02028884) and SAkuraStar (satralizumab monotherapy; NCT02073279). Satralizumab is approved to treat aquaporin-4 IgG-seropositive (AQP4-IgG+) NMOSD. SAkuraBONSAI (NCT05269667) will explore fluid and imaging biomarkers to better understand the mechanism of action of satralizumab and the neuronal and immunological changes following treatment in AQP4-IgG+ NMOSD.

Objectives: …