We will spend the next grant period on epigenetic marks in lung cancer that will build on our previous work on unmasking promoter methylation (Aim 3). We will extend our promoter work to extensively study hypomethylated promoters with a subsequent increase in gene expression for incorporation into EDRN collaborations that focus on RNA or protein (Aim 2). We will assess global methylation status in lung cancer cell lines and primary lung tumors and use new tiled arrays to identify genome-wide regions of methylation (Aim 1). These studies will thus be complementary to our ongoing studies using pharmacologic unmasking and will allow direct comparison between genes methylated in tumors of unclear significance and those that are reactivated after 5-AZA treatment, suggesting a more functional role in tumor progression. Once identified, we will use the assays we developed including MSP and QMSP to test regions of promoter hypermethylation to develop measurable biomarkers. These assays will allow continuing to develop highly specific and sensitive tests to detect tumor cells in various bodily fluids such as serum, plasma, sputum, and BAL fluid for early detection and diagnosis. We have also designed a novel QD-FRET nanoprobe technology for detecting nucleic acids and an additional approach here will be to build these probes for specific methylation markers we discover and validate. The proposed integrated program has the ability to achieve this goal because it optimally applies existing investigator talent, achievement, and interest using the most promising current research directions in epigenetics.
This proposal will comprehensively identify a variety of epigenetic markers in lung cancer. All the proposed aims are unite around the common research goal of generating and applying new molecular markers for the eariy detection and diagnosis of lung cancer. In this way, the morbidity and mortality of this deadly disease may be diminished by eariy and timely detection with appropriate therapy.
|Pirini, Francesca; Noazin, Sassan; Jahuira-Arias, Martha H et al. (2017) Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies. Oncotarget 8:38501-38516|
|Guerrero-Preston, Rafael; White, James Robert; Godoy-Vitorino, Filipa et al. (2017) High-resolution microbiome profiling uncovers Fusobacterium nucleatum, Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis associated to oral and oropharyngeal cancer in saliva from HPV positive and HPV negative patients treated with surgery and Oncotarget 8:110931-110948|
|Guerrero-Preston, Rafael; Godoy-Vitorino, Filipa; Jedlicka, Anne et al. (2016) 16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment. Oncotarget 7:51320-51334|
|Izumchenko, Evgeny; Chang, Xiaofei; Brait, Mariana et al. (2015) Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA. Nat Commun 6:8258|
|Izumchenko, Evgeny; Sun, Kai; Jones, Sian et al. (2015) Notch1 mutations are drivers of oral tumorigenesis. Cancer Prev Res (Phila) 8:277-286|
|Bateman, Nicholas W; Jaworski, Elizabeth; Ao, Wei et al. (2015) Elevated AKAP12 in paclitaxel-resistant serous ovarian cancer cells is prognostic and predictive of poor survival in patients. J Proteome Res 14:1900-10|
|Begum, Shahnaz; Hayashi, Masamichi; Ogawa, Takenori et al. (2015) An integrated genome-wide approach to discover deregulated microRNAs in non-small cell lung cancer: Clinical significance of miR-23b-3p deregulation. Sci Rep 5:13236|
|Kagohara, Luciane Tsukamoto; Schussel, Juliana L; Subbannayya, Tejaswini et al. (2015) Global and gene-specific DNA methylation pattern discriminates cholecystitis from gallbladder cancer patients in Chile. Future Oncol 11:233-49|
|Guo, Mingzhou; Jia, Yan; Yu, Zhengtao et al. (2014) Epigenetic changes associated with neoplasms of the exocrine and endocrine pancreas. Discov Med 17:67-73|
|Maldonado, Leonel; Brait, Mariana; Loyo, Myriam et al. (2014) GSTP1 promoter methylation is associated with recurrence in early stage prostate cancer. J Urol 192:1542-8|
Showing the most recent 10 out of 144 publications