Abstract C061: Inverse correlations between PDLIM7 and let-7 family gene expressions in advanced thyroid cancer tissues from specific racial/ethnic groups

Abstract

Abstract Studies have shown that Asian Americans are more likely to be diagnosed with advanced-stage thyroid cancer than other ethnic groups. Among Asian Americans, Filipino Americans (FA) have the highest thyroid cancer mortality rate compared to different subgroups. FA are known to be three times more likely to die of thyroid cancer than European Americans (EA). African American (AA) and Hispanic American (HA) patients have the worst cancer-specific survival rate compared to EA patients. Epidemiological studies in California have shown that thyroid cancer is the second most common cancer among Filipino American women (1). Although socioeconomic factors play a crucial role in cancer health disparities, thyroid cancer is an exception, where educated FA showed higher incidence/recurrence rates (2). Currently, no studies demonstrate the biological mechanism behind these discrepancies. We are the first to show differential expressions of a tumor suppressor gene (1) and miRNA profiles between FA versus EA (2). We have discovered a new oncogene, PDLIM7, also known as Enigma, with a stage-dependent enhancement in thyroid cancer tissues (3). Our Hiseq-miRNA profiling data showed significant downregulations of one of the well-known tumor suppressor miRNAs, Let-7 family genes. Some of the let-7 family genes are significantly downregulated in FA versus EA (2). Let-7 genes are known to regulate PDLIM family genes. Therefore, we hypothesize that the inverse correlation between PDLIM7 oncogene and Let-7 family genes is linked to advanced thyroid cancer in FA compared to all other ethnicities. In this study, we have expanded our patient cohorts by adding samples from AA and HA to our existing patient cohorts of EA and FA. We determined the differential PDLIM7 gene expression in different ethnic groups using the Cancer Genome Atlas (TCGA) thyroid cancer datasets by UALCAN assay. We also confirmed the PDLIM7 gene and let-7 family expressions by RT-qPCR in different ethnic groups and correlated them to thyroid cancer staging. We found a significantly overexpressed PDLIM7 gene in FA with advanced-stage compared to EA/HA/AA. Among others, PDLIM7 did not show any significant difference. A higher expression of the PDLIM7 gene (*p<0.05) was significantly correlated to let-7 gene downregulation (**p<0.01) in FA patient samples. Our data suggest that an inverse relationship between PDLIM7 and the let-7 gene family in FA correlates to advanced thyroid cancer. Some specific members of let-7 family genes/miRNA-clusters may differentially regulate the PDLIM7 gene in different ethnicities. A future study is underway to reveal the functional regulation of the PDLIM7 gene by specific let-7 family genes. One of the future treatment strategies is to overexpress let-7 family genes by let-7 gene mimics or develop small molecule inhibitors for the PDLIM7 gene and determine the impact on cell death and cell cycle progression both in vitro and in vivo. Citation Format: Jaibir S. Pannu, Kristiana Rood, Celina R. Yamauchi, Alfred A. Simental, Mia C. Perez, Anthony Firek, Salma Khan. Inverse correlations between PDLIM7 and let-7 family gene expressions in advanced thyroid cancer tissues from specific racial/ethnic groups [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C061.