Abstract C056: Prognostic relevance of SUV420H2 (KMT5C) gene expression in clear cell renal cell carcinoma: Implications for patients of African ancestry

Abstract 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 there are racial/ethnic differences in gene and protein expression. Since higher stage/grade ccRCC is uniformly lethal, it is imperative that candidate genes and their corresponding protein products be found that can identify patients across various demographics who are at greater risk of progressing to advanced stage/grade, drug-resistant clear cell renal carcinoma; and that can point to the drivers of ccRCC progression in different demographic groups. Using KIRC (clear cell renal carcinoma) TCGA dataset, we observed that SUV420H2 (KMT5C), a Lysine N-Methyltransferase, is significantly overexpressed in ccRCC (p<1E-12). Moreover, SUV420H2 transcripts were significantly elevated in higher stages and grades (p<.001). Higher SUV420H2 transcripts levels were also correlated with metastasis (p<0.01) and were associated with the more aggressive ccB Renal Csrcinoma phenotype (p<0.001). Overexpression of SUV420H2 was also associated with worst overall patient survival (p<0.0001; HR = 2.05 (1.5151 to 2.79) with a mean survival of 2208 days for the high expression group and 3256 days for the low expression group. Elevated levels were also associated with lower Disease Specific Survival [p<0.0001 HR= 2.7658 (1.8406 to 4.1560)] with a mean survival for the high expression group of 2208 versus 3871 days for the low expression group. Significantly shorter progression free disease times [p<0.0001, HR= 1.9830 (1.4389 to 2.7328) were also observed in the higher expression group (2189 days) relative to the low expression group (2971 days). In addition, in silico data analysis revealed that African Americans exhibited higher expression of SUV420H2 transcripts relative to Whites (p=5.94E-09) and that expression was associated with lower survival outcome (p<0.01, HR=4.33 (1.29 to 14.51). Taken collectively, our data suggests that higher levels of SUV420H2(KMT5C) is associated with cancer progression and the more aggressive ccRCC subtypes. Moreover, SUV420H2 behaves in a manner that suggest it may be a possible oncogene and that it is an unfavorable ccRCC biomarker. Analysis of CPTAC database and Human Protein Atlas failed to yield any information of protein expression in relationship to ccRCC. Given that SUV420H2 functions as a histone methyltransferase that specifically trimethylates histone H4, it is possible that dysregulation could result in altered epigenetic processes and inappropriate repression of genes in ccRCC. Lastly, our data underscores the need for proteomics studies that analyze protein expression differences of putative oncogenes or tumor suppressor genes and proteins across racial and ethnic demographic groups. Citation Format: Romonia Renee Reams, Simone Heyliger, Marilyn Saulsbury. Prognostic relevance of SUV420H2 (KMT5C) gene expression in clear cell renal cell carcinoma: Implications for patients of African ancestry [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 C056.