Clinicopathological and Body Composition Analysis of VHL and TTN Gene Mutations in Clear Cell Renal Cell Carcinoma: An Exploratory Study

Abstract

Background: The Cancer Genome Atlas (TCGA) Research Network revealed numerous clear cell renal cell carcinoma (ccRCC) gene mutations among which titin (TTN). The link between excessive amounts of visceral adipose tissue (VAT) and ccRCC pathogenesis is known. A relationship between VHL and TTN gene mutations and a CT-derived estimation of body composition in ccRCC patients has been evaluated. Methods: We retrospectively assessed patients from the TCGA-kidney renal clear cell carcinoma (KIRC) database for evaluation of clinicopathological and body composition analysis of ccRCC VHL and TTN gene mutations. Results: Gene expression levels and survival were assessed on a large cohort of 483 patients and 533 tumor samples. A statistically significant difference of VHL expression reduction in primary tumor (p < 0.0001) and a TTN expression increase in primary tumor (p < 0.0001) was shown. TTN high expression levels was associated with statistically significant lower KIRC patient survival at eight years (p < 0.05). For body composition analysis, we included 54 male patients divided into two groups: ccRCC-VHL (n = 41) and ccRCC-TTN (n = 13) groups. Statistically significant differences between the two groups were obtained for total adipose tissue (TAT) (p < 0.01), VAT (p < 0.05), subcutaneous adipose tissue (SAT) (p < 0.05) and total abdominal muscle (TAM) (p < 0.05) areas. Conclusion: This study demonstrates a link between ccRCC TTN gene mutation and shorter patient survival. The reduction of the analyzed tissues might be a risk of cancer cachexia in ccRCC patients with TTN gene mutation.