Browsing by Author "Casablanca, Yovanni"

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    Peptide ancestry informative markers in uterine neoplasms from women of European, African, and Asian ancestry
    (Elsevier, 2021-12-23) Bateman, Nicholas W.; Tarney, Christopher M.; Abulez, Tamara S.; Hood, Brian L.; Conrads, Kelly A.; Zhou, Ming; Soltis, Anthony R.; Teng, Pang-Ning; Jackson, Amanda; Tian, Chunqiao; Dalgard, Clifton L.; Wilkerson, Matthew D.; Kessler, Michael D.; Goecker, Zachary; Loffredo, Jeremy; Shriver, Craig D.; Hu, Hai; Cote, Michele; Parker, Glendon J.; Segars, James; Al-Hendy, Ayman; Risinger, John I.; Phippen, Neil T.; Casablanca, Yovanni; Darcy, Kathleen M.; Maxwell, G. Larry; Conrads, Thomas P.; O'Connor, Timothy D.; Medicine, School of Medicine
    Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with disease pathogenesis. Nonsynonymous single-nucleotide polymorphisms encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. In silico analysis identified that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R2 = 0.99). Multiplexed proteomic analysis of >100 human endometrial cancer cell lines and uterine leiomyoma tissues combined resulted in the quantitation of 62 pAIMs that correlate with patient race and genotype-confirmed ancestry. Candidates include a D451E substitution in GC vitamin D-binding protein previously associated with altered vitamin D levels in African and European populations. pAIMs will support generalized proteoancestry assessment as well as efforts investigating the impact of ancestry on the human proteome and how this relates to the pathogenesis of uterine neoplasms.
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    Symptoms of Women With High-Risk, Early-Stage Ovarian Cancer
    (Wolters Kluwer, 2022) Chan, John K.; Tian, Chunqiao; Kesterson, Joshua P.; Monk, Bradley J.; Kapp, Daniel S.; Davidson, Brittany; Robertson, Sharon; Copeland, Larry J.; Walker, Joan L.; Wenham, Robert M.; Casablanca, Yovanni; Spirtos, Nick M.; Tewari, Krishnansu S.; Bell, Jeffery G.; Obstetrics and Gynecology, School of Medicine
    Objective: To assess the presentation, characteristics, and prognostic significance of symptoms in patients with high-risk early-stage epithelial ovarian cancer. Methods: A retrospective chart review was performed on all patients enrolled in a phase III clinical trial (GOG 157). All patients had surgically staged, high-risk early-stage epithelial ovarian cancer (stage IA-IB and grade 3, any clear cell, stage IC or II). Chi-square and Kaplan-Meier estimates and Cox proportional hazards models were used for statistical analyses. Results: Of 419 patients evaluated for symptoms, 301 (72%) presented with one or more symptoms, and 118 (28%) were asymptomatic but had a mass found on examination. Forty percent had only one symptom, and 32% had more than one symptom. Among those with at least one symptom, the most common were abdominal and pelvic pain (31%), and increased girth or fullness (26%). Overall, 23% of patients with tumors 10 cm or smaller, 27% of patients with tumors larger than 10 cm to 15 cm, and 46% of patients with tumors larger than 15 cm had multiple symptoms (P<.001). There was no significant difference in presentation of symptoms based on age, stage, or histologic subtype. Symptoms at diagnosis were not associated with recurrence or survival. Conclusion: More than 70% of patients with high-risk early-stage, epithelial ovarian cancer present with one or more symptoms, with the most common being abdominal or pelvic pain. The proportion of women with symptoms and the number of symptoms increase with enlarging tumor size.