Abstract C030: Gene expression profiling tumors of patients with clear cell renal carcinoma: May identify race-specific therapeutic targets

Abstract

Black/African Americans are second only to Native Americans in having the highest incidence of renal cancer. Despite this statistic, very few studies have examined whether patients’ tumors exhibit racial/ethnic differences in both gene and/or protein expression. Using KIRC (clear cell renal carcinoma) TCGA dataset (n=542), we identified several genes that were significantly overexpressed in ccRCC derived from Blacks.  Genes which showed significantly higher expression in tumors from Blacks (n=56) relative to Whites (n=463) included ADCK5 (adj p<0.001) ADRM1 (adj p=0.013), ANKRD13D (adj p=0.003), ARFGAP1 (adj p=.003), LZTS2 (adj p<0.001), FAM160B2 (adj p<0.001), and NCKAP5L (adj p=0.029).  In addition, these genes were also significantly overexpressed (p<0.05) in advanced stages, higher grades as well as in metastatic tissues. Multivariate cox regression analysis of gene expression, ethnicity, racial demographics and clinicopathological features relative to overall survival time revealed that ARFGAP1 (HRadj=2.40 [95% CI: 1.37 to 4.22]), ANKRD13D (HRadj=2.56 [95% CI:1.43 to 4.59]), FAM160B2 (HRadj= 1.74 [95%CI: 1.01 to 2.99]), and NCKAP5L (HRadj= 1.88 [95% CI:1.04 to 3.41])  were independent prognostic markers for survival. Higher expression of ADCK5 (HRadj= 5.98[CI:1.26-28.35], p=0.012), ADMR1 (HRadj= 1.74 [95%CI: 1.05 to 11.38], p=0.03), ANKRD13D (HRadj= 9.05 [95%CI: 1.13 to 72.66], p=0.014), ARFGAP1 (HRadj=3.79 [95% CI: 0.097-14.54], p=0.041), FAM160B2 (HRadj=5.09 [95%CI: 1.01-25.75], p=0.033),   LZTS2 (HRadj=3.32 [95%CI: 1.01-10.99], p=0.037) was associated with lower ccRCC survival in Blacks. ROC analysis indicated that expression of FAM160B2 and LZTS2 are strong predictors of ccRCC survival among Blacks (AUC= 0.737, p<0.001, AUC= 0.731, p<0.001, respectively), whereas ADCK5 and ADRM1, (AUC=0.692, p<0.001, AUC=0.625, p=0.001, respectively) were moderate predictors of ccRCC survival among Blacks.  FAM160B2 (family with sequence similarity 160 member B2) is a protein kinase A anchoring protein (AKAP) and participates in PKA (protein kinase A) phosphorylation of HSP70 (heat shock protein 70). FAM160B2 is also involved in hepatocellular carcinoma and promotes tumorigenesis. LZTS2, which encodes leucine zipper tumor suppressor 2, was identified as a tumor susceptibility gene within the 10q24.3 chromosomal region and is approximately 15Mb from the PTEN locus. This region containing both loci is frequently deleted in a variety of human malignancies, including prostate cancer. Taken collectively our data suggest that the aforementioned genes, FAM160B2 and LZTS2 may be useful both as clinical biomarkers and should be explored as potential therapeutic targets for ccRCC, with possible greater impact among Black patients.

Citation Format: Romonia Renee Reams, Simone O. Heyliger, Marilyn Saulsbury, Emanuela Taioli, Diana Wilkie, John Carpten. Gene expression profiling tumors of patients with clear cell renal carcinoma: May identify race-specific therapeutic targets [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C030.