Investigator

Vincent Wagner

Assistant Professor · University of Iowa, Division of Gynecologic Oncology

VWVincent Wagner
Papers(4)
A Natural Language Pr…Training, Validating,…Identification of Ova…Transforming Gynecolo…
Collaborators(10)
Jesus Gonzalez-BosquetAndrew PolioBodour SalhiaBradley R. CorrBrandon M. SchicklingCasey M. CosgroveErin GeorgeMarilyn S. HuangRob L. DoodAhmad A. Tarhini
Institutions(7)
University Of IowaUniversity Of Souther…University Of Colorad…The Ohio State Univer…Moffitt Cancer CenterCancer Center at the …University of Pennsyl…

Papers

A Natural Language Processing Method Identifies an Association Between Bacterial Communities in the Upper Genital Tract and Ovarian Cancer

Bacterial communities within the female upper genital tract may influence the risk of ovarian cancer. In this retrospective cohort pilot study, we aim to detect different communities of bacteria between ovarian cancer and normal controls using topic modeling, a natural language processing tool. RNA was extracted and analyzed using the VITCOMIC2 pipeline. Topic modeling assessed differences in bacterial communities. Idatuning identified an optimal latent topic number and Latent Dirichlet Allocation (LDA) assessed topic differences between high-grade serous ovarian cancer (HGSOC) and controls. Results were validated using The Cancer Genome Atlas (TCGA) HGSOC dataset. A total of 801 unique taxa were identified, with 13 bacteria significantly differing between HGSOC and normal controls. LDA modeling revealed a latent topic associated with HGSOC samples, containing bacteria Escherichia/Shigella and Corynebacterineae. Pathway analysis using KEGG databases suggest differences in several biologic pathways including oocyte meiosis, aldosterone-regulated sodium reabsorption, gastric acid secretion, and long-term potentiation. These findings support the hypothesis that bacterial communities in the upper female genital tract may influence the development of HGSOC by altering the local environment, with potential functional implications between HGSOC and normal controls. However, further validation is required to confirms these associations and determine mechanistic relevance.

Training, Validating, and Testing Machine Learning Prediction Models for Endometrial Cancer Recurrence

PURPOSE Endometrial cancer (EC) is the most common gynecologic cancer in the United States with rising incidence and mortality. Despite optimal treatment, 15%-20% of all patients will recur. To better select patients for adjuvant therapy, it is important to accurately predict patients at risk for recurrence. Our objective was to train, validate, and test models of EC recurrence using lasso regression and other machine learning (ML) and deep learning (DL) analytics in a large, comprehensive data set. METHODS Data from patients with EC were downloaded from the Oncology Research Information Exchange Network database and stratified into low risk, The International Federation of Gynecology and Obstetrics (FIGO) grade 1 and 2, stage I (N = 329); high risk, or FIGO grade 3 or stages II, III, IV (N = 324); and nonendometrioid histology (N = 239) groups. Clinical, pathologic, genomic, and genetic data were used for the analysis. Genomic data included microRNA, long noncoding RNA, isoforms, and pseudogene expressions. Genetic variation included single-nucleotide variation (SNV) and copy-number variation (CNV). In the discovery phase, we selected variables informative for recurrence ( P < .05), using univariate analyses of variance. Then, we trained, validated, and tested multivariate models using selected variables and lasso regression, MATLAB (ML), and TensorFlow (DL). RESULTS Recurrence clinic models for low-risk, high-risk, and high-risk nonendometrioid histology had AUCs of 56%, 70%, and 65%, respectively. For training, we selected models with AUC >80%: five for the low-risk group, 20 models for the high-risk group, and 20 for the nonendometrioid group. The two best low-risk models included clinical data and CNVs. For the high-risk group, three of the five best-performing models included pseudogene expression. For the nonendometrioid group, pseudogene expression and SNV were overrepresented in the best models. CONCLUSION Prediction models of EC recurrence built with ML and DL analytics had better performance than models with clinical and pathologic data alone. Prospective validation is required to determine clinical utility.

Identification of Ovarian High-Grade Serous Carcinoma with Mitochondrial Gene Variation

Women diagnosed with advanced-stage ovarian cancer have a much worse survival rate than women diagnosed with early-stage ovarian cancer, but the early detection of this disease remains a clinical challenge. Some recent reports indicate that genetic variations could be useful for the early detection of several malignancies. In this pilot observational retrospective study, we aimed to assess whether mitochondrial DNA (mtDNA) variations could discriminate the most frequent type of ovarian cancer, high-grade serous carcinoma (HGSC), from normal tissue. We identified mtDNA variations from 20 whole-exome sequenced (WES) HGSC samples and 14 controls (normal tubes) using the best practices of genome sequencing. We built prediction models of cancer with these variants, with good performance measured by the area under the curve (AUC) of 0.88 (CI: 0.74–1.00). The variants included in the best model were correlated with gene expression to assess the potentially affected processes. These analyses were validated with the Cancer Genome Atlas (TCGA) dataset, (including over 420 samples), with a fair performance in AUC terms (0.63–0.71). In summary, we identified a set of mtDNA variations that can discriminate HGSC with good performance. Specifically, variations in the MT-CYB gene increased the risk for HGSC by over 30%, and MT-CYB expression was significantly decreased in HGSC patients. Robust models of ovarian cancer detection with mtDNA variations could be applied to liquid biopsy technology, like those which have been applied to other cancers, with a special focus on the early detection of this lethal disease.

21Works
4Papers
11Collaborators
Ovarian NeoplasmsEarly Detection of CancerEndometrial NeoplasmsNeoplasm Recurrence, LocalCystadenocarcinoma, SerousNeoplasm Grading

Positions

Assistant Professor

University of Iowa · Division of Gynecologic Oncology

Links & IDs
0000-0002-0402-3483

Scopus: 57204636908