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Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang

Dartmouth College Ph.D Dissertations

DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …

Hyperoxidized Prdx3 As A Specific Ferroptosis Marker, Yuelong Yan, Boyi Gan

Student and Faculty Publications

The lack of a reliable and specific marker for ferroptosis has hindered the advancement of treatments related to this cell death mechanism toward clinical application. A recent study published in Molecular Cell has identified hyperoxidized peroxiredoxin 3 (PRDX3) as a promising marker for ferroptosis, opening up new avenues for monitoring and targeting ferroptosis in disease treatment.

Metabolomic Insights Into Tuberculosis: Machine Learning Approaches For Biomarker Identification, Miftahul Khair Akbar, Arief Aulia Rahman

Indonesian Journal of Medical Chemistry and Bioinformatics

The lung parenchyma is largely impacted by the infectious condition known as pulmonary tuberculosis (pulmonary TB) when the immune system creates a wall around the germs in the lungs, a tiny, hard bulge known as a tubercle develops, earning the disease the name tuberculosis. Although the majority of TB germs target the lungs, they can also harm other bodily organs. The identification of TB biomarkers, which are crucial for diagnosis, treatment monitoring, risk analysis, and prognosis, has been the subject of extensive research. Differences in metabolites between normal cells and tuberculosis are considered to be able to support the diagnosis …

A Blood-Based Metabolomic Signature Predictive Of Risk For Pancreatic Cancer, Ehsan Irajizad, Ana Kenney, Tiffany Tang, Jody Vykoukal, Ranran Wu, Eunice Murage, Jennifer B Dennison, Marta Sans, James P Long, Maureen Loftus, John A Chabot, Michael D Kluger, Fay Kastrinos, Lauren Brais, Ana Babic, Kunal Jajoo, Linda S Lee, Thomas E Clancy, Kimmie Ng, Andrea Bullock, Jeanine M Genkinger, Anirban Maitra, Kim-Anh Do, Bin Yu, Brian M Wolpin, Sam Hanash, Johannes F Fahrmann

Student and Faculty Publications

Emerging evidence implicates microbiome involvement in the development of pancreatic cancer (PaCa). Here, we investigate whether increases in circulating microbial-related metabolites associate with PaCa risk by applying metabolomics profiling to 172 sera collected within 5 years prior to PaCa diagnosis and 863 matched non-subject sera from participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. We develop a three-marker microbial-related metabolite panel to assess 5-year risk of PaCa. The addition of five non-microbial metabolites further improves 5-year risk prediction of PaCa. The combined metabolite panel complements CA19-9, and individuals with a combined metabolite panel + CA19-9 score in the …

The Characterization And Evaluation Of The Soluble Triggering Receptor Expressed On Myeloid Cells-Like Transcript-1 In Stable Coronary Artery Disease, Zaida Bayrón-Marrero, Siobhan Branfield, Javier Menéndez-Pérez, Benjamín Nieves-López, Laura Ospina, Yadira Cantres-Rosario, Loyda M Melendez, Robert Hunter, Angelia Gibson, Gerónimo Maldonado-Martínez, A Valance Washington

Student and Faculty Publications

Platelets play crucial roles in the development and progression of coronary artery disease (CAD). The triggering receptor expressed in myeloid cells-like transcript-1 (TLT-1) is stored in platelet α granules, and activated platelets release a soluble fragment (sTLT-1). We set out to better characterize the constituent amino acids of sTLT-1 and to evaluate sTLT-1 for use as a biomarker in patients with stable CAD. We evaluated sTLT-1 release using immunoprecipitation and mass spectrometry and employed statistical methods to retrospectively correlate sTLT-1 concentrations, utilizing ELISA in plasma samples from 1510 patients with documented stable CAD. We identified TLT-1 residues to 133 in …

Clinical And Prognostic Biomarker Value Of Blood-Circulating Inflammatory Cytokines In Hepatocellular Carcinoma, Shadi Chamseddine, Yehia I Mohamed, Sunyoung S Lee, James C Yao, Zishuo Ian Hu, Hop S Tran Cao, Lianchun Xiao, Ryan Sun, Jeffrey S Morris, Rikita I Hatia, Manal Hassan, Dan G Duda, Maria Diab, Amr Mohamed, Ahmed Nassar, Saumil Datar, Hesham M Amin, Ahmed Omar Kaseb

Student and Faculty Publications

INTRODUCTION: Circulating inflammatory cytokines play critical roles in tumor-associated inflammation and immune responses. Recent data have suggested that several interleukins (ILs) mediate carcinogenesis in hepatocellular carcinoma (HCC). However, the predictive and prognostic value of circulating ILs is yet to be validated. Our study aimed to evaluate the association of the serum ILs with overall survival (OS) and clinicopathologic features in a large cohort of HCC patients.

METHODS: We prospectively collected data and serum samples from 767 HCC patients treated at the University of Texas MD Anderson Cancer Center between 2001 and 2014, with a median follow-up of 67.4 months (95% …

Presence Of Circulating Tumor Cells Predates Imaging Detection Of Relapse In Patients With Stage Iii Melanoma, Anthony Lucci, Sridevi Addanki, Yi-Ju Chiang, Salyna Meas, Vanessa N Sarli, Joshua R Upshaw, Mayank Manchem, Sapna P Patel, Jennifer A Wargo, Jeffrey E Gershenwald, Merrick I Ross

Student and Faculty Publications

Stage III melanoma includes nodal metastasis or in-transit disease. Five-year survival rates vary between 32% and 93%. The identification of high-risk patients is important for clinical decision making. We demonstrated previously that ≥1 circulating tumor cells (CTCs) at baseline was associated with recurrence. In this study, we investigated how frequently CTCs were identified prior to radiologically detected recurrence. Stage III patients (n = 325) had imaging at baseline and q 3 months. Baseline and q 6-12 months blood draws (7.5 mL) were performed to identify CTCs up to 3.5 years from diagnosis. CTC assessment was performed using the immunomagnetic …

Targeting The Molecular And Immunologic Features Of Leiomyosarcoma, Brandon M Cope, Raymond S Traweek, Rossana Lazcano, Emily Z Keung, Alexander J Lazar, Christina L Roland, Elise F Nassif

Student and Faculty Publications

Leiomyosarcoma (LMS) is a rare, aggressive mesenchymal tumor with smooth muscle differentiation. LMS is one of the most common histologic subtypes of soft tissue sarcoma; it most frequently occurs in the extremities, retroperitoneum, or uterus. LMS often demonstrates aggressive tumor biology, with a higher risk of developing distant metastatic disease than most sarcoma histologic types. The prognosis is poor, particularly in patients with uterine disease, and there is a need for the development of more effective therapies. Genetically, LMS is karyotypically complex and characterized by a low tumor mutational burden, with frequent alterations in TP53, RB1, PTEN, …

Circulating Neutrophils And Tumor-Associated Myeloid Cells Function As A Powerful Biomarker For Response To Chemoradiation In Locally Advanced Cervical Cancer, Olsi Gjyshi, Adam Grippin, Lauren Andring, Anuja Jhingran, Lilie L Lin, Julianna Bronk, Patricia J Eifel, Melissa M Joyner, Jagannadha K Sastry, Kyoko Yoshida-Court, Travis N Solley, Tatiana Cisneros Napravnik, Madison P O'Hara, Venkatesh L Hegde, Lauren E Colbert, Ann H Klopp

Student and Faculty Publications

PURPOSE: The immune system's role in mediating the cytotoxic effects of chemoradiotherapy remains not completely understood. The integration of immunotherapies into treatment will require insight into features and timing of the immune microenvironment associated with treatment response. Here, we investigated the role of circulating neutrophils and tumor-associated myeloid cells (TSAMs) as potential agents and biomarkers for disease-related outcomes in locally advanced cervical cancer (LACC).

MATERIAL AND METHODS: Hematologic parameters for two LACC patient cohorts, a retrospective clinical and a prospective translational cohort, were obtained at baseline, weekly during chemoradiotherapy for the retrospective cohort, biweekly during chemoradiotherapy for the prospective cohort, …

Clinical Features Associated With Outcomes And Biomarker Analysis Of Dabrafenib Plus Trametinib Treatment In Patients With Braf-Mutant Melanoma Brain Metastases, James S Wilmott, Hussein Tawbi, Johnathan A Engh, Nduka M Amankulor, Brindha Shivalingam, Hiya Banerjee, Ismael A Vergara, Hansol Lee, Peter A Johansson, Peter M Ferguson, Philippe Saiag, Caroline Robert, Jean-Jacques Grob, Lisa H Butterfield, Richard A Scolyer, John M Kirkwood, Georgina V Long, Michael A Davies

Student and Faculty Publications

PURPOSE: This study aimed to identify baseline clinical features associated with the outcomes of patients enrolled in the COMBI-MB phase II study of dabrafenib and trametinib treatment in patients with V600 BRAF-mutant metastatic melanoma with melanoma brain metastases (MBM). Exploratory biomarker analysis was also conducted as part of the synergistic COMBI-BRV trial (BRV116521), to identify molecular and immunologic changes associated with dabrafenib in MBMs and extracranial metastases (ECM).

PATIENTS AND METHODS: Post hoc analysis was performed for baseline features of patients (n = 125) enrolled in COMBI-MB. Analyses were performed to identify baseline clinical features associated with intracranial response rate …

Il-8 Produced Via Bidirectional Communication Between Prostate Cancer And M2 Macrophages As A Potential Diagnostic And Prognostic Biomarker, Huihui Fan, Zheng Tang, Yaling Tian, Qingsong Lv, Fangyin Zeng

Student and Faculty Publications

PURPOSE: Owing to the mortality associated with metastatic prostate cancer and the shortcomings of the current parameters in predicting the disease prognosis, we require the identification of viable biomarkers, which would help in the diagnosis and prognosis of the disease. We aimed to determine whether the interleukin-8 level in the tumor microenvironment could serve as a potential clinical diagnostic marker and prognostic factor for prostate cancer.

METHODS: The migration assay of prostate cancer cells was performed in an in vitro co-culture model. Cell lines PC3 and DU145 were divided into two groups and co-cultured with M0 and M2 macrophages, respectively. …