Ponce Banner
 

Pilot Research Project: Evaluation of gene expression signatures predictive of disease aggressiveness and chemoresistance in Puerto Rican men with prostate cancerCarlos Diaz Osterman, PhD (PHSU) and Kosj Yamoah, MD, PhD (MCC)

Pilot Research Project: Adaptation of an HPV education resource to promote HPV vaccination among unvaccinated Spanish language-preferring YLMSM in Puerto Rico and Florida Shannon Christy, PhD (MCC) and Melissa Marzán-Rodríguez, DrPH (PHSU)

Pilot Research Project: The epigenetic predictors of aggressive prostate cancer in Puerto Rican men – Jong Park, PhD (MCC); Gilberto Ruiz-Deyá, MD (PHSU); Anders Berglund, PhD (MCC); and Jaime Matta, PhD (PHSU)

Pilot Research Project: Stress-related signal transduction in ovarian cancerGuillermo Armaiz-Peña, PhD (PHSU) and Alvaro Monteiro, PhD (MCC)


Pilot Research Project: Evaluation of gene expression signatures predictive of disease aggressiveness and chemoresistance in Puerto Rican men with prostate cancer – Carlos Diaz Osterman, PhD (PHSU) and Kosj Yamoah, MD, PhD (MCC)

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and the second leading cause of cancer deaths in the United States. African American (AA) men are more likely to develop and die from PCa than European American (EA) men, while Hispanic/Latino (H.L) men experience the disease trajectories similar to EA men. However, differentiation of H/L subgroups with PCa by country of origin reveals heterogeneity in tumor aggressiveness among Hispanics, with Puerto Rican (PR) men experiencing survival outcomes that approximate those of AA men. PR men carry roughly three times the African ancestry of the overall H/L population, and it is possible that shred genetic ancestry may provide an indication of similarly aggressive tumor biology. Since risk assessment is the foundation of clinician-patient decision making for PCa treatment, it is critical to improve the predictive value of risk assessment tools to enhance their ability to identify patients harboring aggressive tumor phenotypes. Recent advances in genomic testing using the Decipher genome-wide expression-based assay of prostate biopsies and tumor specimens allows for prediction of response to docetaxel, the current standard of care chemotherapeutic agent for advanced PCa. However, the use of this test has only recently been validated in AA men with PCa, and its use in PR men has yet to be determined. Furthermore, the molecular pathways contributing to docetaxel resistance in PCa are currently unknown, which limits the further tuning of predictive tools using docetaxel-resistance gene signatures as well as the rationale-based targeting of chemoresistant tumors. This pilot study aims to (1) systematically identify pathways associated with oncogene-driven docetaxel resistance in PCa cells, and (2) evaluate, for the first time, the Decipher genomic risk assessment tool in PR men, compared with EA and AA men with PCa, for its efficacy in predicting clinical outcomes and docetaxel response.

Back to Top


Pilot Research Project: Adaptation of an HPV education resource to promote HPV vaccination among unvaccinated Spanish language-preferring YLMSM in Puerto Rico and Florida – Shannon Christy, PhD (MCC) and Melissa Marzán-Rodríguez, DrPH (PHSU)

Persistent infections from oncogenic human papillomavirus (HPV) strains can develop into several types of cancers in both men and women. Multiple HPV-related disparities exist. For example, geographic disparities in both HPV-related cancer incidence and mortality and HPV vaccine uptake affect individuals in Puerto Rico (PR) and Florida (FL). Furthermore, HPV disproportionately affects men who have sex with men (MSM). Despite their increased risk for HPV infection, only 13.7% of MSM report receiving the HPV vaccine. Educational interventions that promote HPV vaccination are critical to prevent HPV-related cancer incidence and mortality among this high-risk and underserved group. However, no educational interventions targeted to Spanish-speaking MSM exist. Building upon an existing Spanish-language Cancer 101 HPV educational module developed for the Hispanic community as part of the U54 Outreach Core, we seek to culturally adapt and refine the module for a new intended and more specific audience: Spanish-preferring young Latino MSM (YLMSM) ages 18-26 years old.

Back to Top


Pilot Research Project: The epigenetic predictors of aggressive prostate cancer in Puerto Rican men – Jong Park, PhD (MCC); Gilberto Ruiz-Deyá, MD (PHSU); Anders Berglund, PhD (MCC); and Jaime Matta, PhD (PHSU)

Incidence and mortality rates among Hispanic/Latino men with prostate cancer (PCa) are nearly the same as non-Hispanic whites (NHW) men. However, these data may be over-generalized because all Hispanic/Latino subgroups are aggregated into one broad group. Few studies focus on health disparities of PCa in Puerto Rican (PR) men. Data from the PR Cancer Registry shows that PCa is the leading cancer in PR men, in incidence and mortality. Recent studies reported that Hispanic PR men have a higher rate of poorer outcomes than NHW. Epigenetic alterations play a critical role in cancer progression. Dysregulation of DNA methylation has been investigated extensively by us and others as a promising biomarker for PCa progression. The DNA methylation variant 5-hydromethylcytosine (5hmC) has recently emerged as a new biomarker candidate. Our preliminary data clearly suggest that DNA methylation and 5hmC may contribute to PCa progression. In addition, one key molecular feature of PCa progression is the dysregulation of DNA repair genes. Motivated by these data, we propose to investigate further epigenetic differences between PR and NHW men to identify PR-specific biomarkers for PCa using tissues from the PR BioBank and Moffitt. We propose to incorporate ancestry structure in the progression of PCa. Patients will be clustered into ancestral groups on the basis of ancestry informative genetic variation extracted from genome-wide association study (GWAS) genotyping panel with support from the PHSU-MCC Partnership Quantitative Sciences Core. We anticipate that our study will identify PR specific biomarkers, indicate prognosis of PR men. Our findings may help to design better strategies for PCa specific prevention and treatment for PR men. For future studies, this novel PR prostate cancer gene signature will be validated by larger PR cohorts.

Back to Top


Pilot Research Project: Stress-related signal transduction in ovarian cancer – Guillermo Armaiz-Peña, PhD (PHSU) and Alvaro Monteiro, PhD (MCC)

There is strong evidence for a role of stress in cancer. Work from our group and others has shown that psychological states such as chronic stress or depression may accelerate growth of existing tumors and promote chemoresistance. Importantly, a significant number of ovarian cancer patients are clinically depressed or lack social support. These emotional states have been linked to sustained activation of the sympathetic nervous system and decreased survival. Our preliminary data in immortalized ovarian and fallopian tube epithelial cells suggests that the homeotic transcription factor HOXA5 plays a central role in the early transcriptional response to norepinephrine. Interestingly, norepinephrine seems to be unable to induce HOXA5 in cancer cells. In addition to profound changes in the transcriptional program, we have also shown that NE exposure causes DNA double-stranded break damage in EOC cells in a β-adrenergic receptor-dependent manner. Interestingly, combined treatment of NE and Cisplatin, a DNA-damaging agent which is a mainstay of ovarian cancer therapy, led to levels of DNA damage significantly lower than either treatment alone. This suggests a potential mechanism by which stress can influence chemotherapy efficacy. These observations provide two potential sites of intervention to mitigate the effects of stress on ovarian cancer. We will clarify the role of NE in EOC through the following aims: 1) Determine the extent to which adrenergic-induced transcriptional changes are mediated by HOXA5; and 2). Determine the contribution of adrenergic signaling to chemoresistance in ovarian cancer cells. This proposal will provide the groundwork for additional research on precision medicine by linking psychological risk factors with underlying tumor biology.

Back to Top