High expression of karyopherin alpha 2 (KPNA2), a carrier protein that helps shuttle cancer-associated proteins from the nucleus to the cytoplasm, is an adverse prognostic factor in patients with clear cell or papillary renal cell carcinoma (RCC), according to a retrospective cohort study.
Senior author, director of the Institute of Pathology at the University Hospital Bonn (Germany), and his colleagues assessed tumor levels of KPNA2 protein by immunohistochemistry in 240 clinic patients with RCC (217 with clear cell histology, 23 with papillary histology). They also assessed tumor levels of KPNA2 mRNA in 771 patients with RCC (481 with clear cell histology, 290 with papillary cell histology) using publicly available gene expression data from the Cancer Genome Atlas (CGA).
Overall, 19% of the clinic patients’ tumors showed high expression of KPNA2 protein, according to results reported in. In addition, 26% of the CGA patients’ tumors showed high expression of KPNA2 mRNA.
Among patients with clear cell RCC, those with high tumor levels of KPNA2 protein survived roughly half as long as counterparts with low levels or none (74 months vs. 171 months); the difference was significant in univariate analysis (P = .012) but not in multivariate analysis that included well-known prognostic factors (HR, 1.491; P = .237). On the other hand, those with high tumor levels of KPNA2 mRNA had an elevated risk of death in both univariate analysis (HR, 2.31; P less than .001) and multivariate analysis (HR, 1.45; P = .035).
Among patients with papillary RCC, tumor levels of KPNA2 protein were not significantly associated with survival. However, those with high tumor levels of KPNA2 mRNA had a sharply elevated risk of death in both univariate analysis (HR, 9.7; P less than .001) and multivariate analysis (HR, 6.2; P = .004).
KPNA2 expression “represents a novel prognostic factor in these subtypes of RCC,” concluded Dr. Kristiansen and his coinvestigators. Therefore, this biomarker “could be used to stratify risk groups within RCC.” Collectively, the study’s findings suggest that KPNA2 is involved in both the pathogenesis and the progression of RCC. Given evidence that it helps transport p53 and fibroblast growth factor 2 at least in tumors with clear cell histology, “investigation of the nucleocytoplasmic transport through KPNA2 in [clear cell] RCC is an important task for future studies to better understand the link between elevated KPNA2 expression and altered biological processes like proliferation, cell growth, migration, invasion and tumor formation in RCC. In addition, examination of other members of [the] karyopherin-alpha family could elucidate the role of the nucleocytoplasmic transport system in pathogenesis of RCC.”
The authors reported that they had no conflict of interests.
SOURCE: Kristiansen G et al. Clin Genitourin Cancer. 2018 Oct 22. .