Prognostic relevance of ZNF668 expression in clear cell renal carcinoma: Implications for patients of African Ancestry

Although the incidence of clear cell renal carcinoma (ccRCC) is higher in Whites, a recent report suggests Blacks suffer worst outcomes relative to White ccRCC patients. These observations underscore the need to determine the molecular basis for survival disparity among Blacks and Whites in clear cell renal carcinoma patients. Since higher stage/grade ccRCC is uniformly lethal, it is imperative that biomarkers and candidate genes be found that can identify patients at greater risk of progressing to advanced stage/grade, drug-resistant clear cell renal carcinoma, as well as that, can point to the drivers of ccRCC progression in different demographic groups. Using KIRC (clear cell renal carcinoma) TCGA dataset, we have observed that ZNF668, a KRAB zinc-finger transcription factor, is significantly overexpressed in ccRCC (p=1.62E-12). Moreover, ZNF668 transcripts were significantly elevated in higher stages and grades (p<.001). Higher ZNF668 transcripts levels were also correlated with metastasis (p<0.01) and were associated with the more aggressive ccB phenotype (p<0.001). Overexpression was also associated with more unsatisfactory overall patient survival (p<.001; HR = 1.76 (1.3 − 2.37) with a median survival of 66 months for the high expression group compared to 120 months for the low expression. In addition, we observed that Blacks exhibited higher expression of ZNF668 transcripts relative to Whites (p=2.22E-04). Taken collectively, data suggests that higher levels of ZNF668 is associated with cancer progression and more aggressive ccRCC subtypes. Moreover, ZNF668 behaves in a manner that indicates that it is a negative prognostic marker and a possible oncogene in clear cell renal cell carcinoma. Lastly, higher expression in Blacks suggests this population may be particularly at risk for developing more aggressive forms of ccRCC. Citation Format: R. Renee Reams, Simone O. Heyliger, Marilyn Saulsbury. Prognostic relevance of ZNF668 expression in clear cell renal carcinoma: Implications for patients of African Ancestry [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-151.