Clear cell renal cell carcinoma molecular variations in non‐Hispanic White and Hispanic patients

• Published in: Cancer medicine (Malden, MA) Vol. 12; no. 11; pp. 12792 - 12801
• Main Authors: Batai, Ken, Chen, Yuliang, Rheinheimer, Brenna A., Arora, Amit, Pandey, Ritu, Heimark, Ronald L., Bracamonte, Erika R., Ellis, Nathan A., Lee, Benjamin R.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.06.2023; John Wiley and Sons Inc; Wiley
• Subjects: Biomarkers; Body mass index; Clear cell-type renal cell carcinoma; Diabetes; Ethnicity; Gene expression; gene expression and diversity Hispanics and European Americans (comparison); Genomes; Genomics; Haptoglobin; health disparities; Hispanic Americans; Hypertension; Kidney cancer; Medical records; Minority & ethnic groups; molecular subtype; Mortality; Mutation; Obesity; Patients; Population studies; Race; Regression analysis; Variance analysis; Variation; VHL; VHL protein; United States > US; health disparities; VHL; molecular subtype; gene expression and diversity Hispanics and European Americans (comparison)
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.5929

Background The United States is becoming increasingly diverse, but few molecular studies have assessed the progression of clear cell renal cell carcinoma (ccRCC) in diverse patient populations. This study examined ccRCC molecular variations in non‐Hispanic White (NHW) and Hispanic patients and their effect on the association of gene expression with high‐grade (Grade 3 or 4) ccRCC and overall mortality. Methods A total of 156 patients were included in VHL sequencing and/or TempO‐Seq analysis. DESeq2 was used to identify the genes associated with high‐grade ccRCC. Logistic regression analysis was performed to assess whether race and ethnicity was associated with high/moderate impact VHL somatic mutations and the ccA/ccB subtype. Cox regression analysis was performed to assess association of molecular subtype and gene expression with overall mortality. Results NHWs had moderate or high impact mutations in the VHL gene at a higher frequency than Hispanics (40.2% vs. 27.4%), while Hispanics had a higher frequency of the ccA subtype than NHWs (61.9% vs. 45.8%). ccA was more common in patients with BMI≥35 (65.2%) than in those with BMI < 25 (45.0%). There were 11 differentially expressed genes between high‐ and low‐grade tumors. The Haptoglobin (HP) gene was most significantly overexpressed in high‐ compared to low‐grade ccRCC in all samples (p‐adj = 1.7 × 10−12). When stratified by subtype, the 11 genes were significantly differentially expressed in the ccB subtype, but none of them were significant after adjusting for multiple testing in ccA. Finally, patients with the ccB subtype had a significantly increased risk of overall mortality (HR 4.87; p = 0.01) compared to patients with ccA, and patients with high HP expression and ccB, had a significantly increased risk of mortality compared to those with low HP expression and ccA (HR 6.45, p = 0.04). Conclusion This study reports ccRCC molecular variations in Hispanic patients who were previously underrepresented. Clear cell renal cell carcinoma is an obesity‐related subtype of kidney cancer which is unevenly affecting racial and ethnic minority groups. Hispanics have different molecular characteristics from non‐Hispanic Whites, potentially due to different prevalence of risk factors. Molecular variations likely impact use of molecular biomarkers to assess disease progression in diverse patient populations.