TPX2 as a prognostic indicator and potential therapeutic target in clear cell renal cell carcinoma

Abstract

Objectives: Our aims were to determine if targeting protein for Xklp2 (TPX2) is correlated with clear cell renal cell carcinoma (ccRCC) histology and oncologic outcomes using The Cancer Genome Atlas (TCGA) and an institutional tissue microarray (TMA).

Methods: Clinicopathological data obtained from the TCGA consisted of 415 samples diagnosed with ccRCC. A TMA was constructed from tumors of 207 patients who underwent radical nephrectomy for ccRCC. TPX2 expression by immunohistochemistry on TMA was assessed by a genitourinary pathologist. Clinical data were extracted and linked to TMA cores. TPX2 and Aurora-A mRNA coexpression were evaluated in the TCGA cohort. Overall survival (OS), cancer-specific survival, and recurrence-free survival (RFS) were analyzed using the Kaplan-Meier method and log-rank statistics. Univariate and multivariate analyses were conducted using Cox proportional hazard models.

Results: Median follow-up time for the TCGA cohort was 3.07 years. Aurora-A and TPX2 mRNA coexpression were significantly correlated (Pearson correlation = 0.918). High TPX2 mRNA expression was associated with advanced stage, metastasis, poor OS, and RFS. Median follow-up time for the TMA cohort was 5.3 years. Elevated TPX2 protein expression, defined as greater than 75th percentile staining intensity, was identified in 47/207 (22.7%) patients. Increased TPX2 immunostaining was associated with poor OS (P = 0.0327, 53% 5-year mortality), cancer-specific survival (P<0.01, 47.8% 5-year cancer-specific mortality), RFS (P = 0.0313, 73.6%, 5-year recurrence rate), grade, T stage, and metastasis. Multivariate analysis demonstrated elevated expression served as an independent predictor of RFS (hazard ratio = 3.62 (1.13-11.55), P = 0.029).

Conclusions: We show TPX2, a regulator of Aurora-A, is associated with high grade and stage of ccRCC, and is an independent predictor of recurrence. Future studies are warranted testing its role in ccRCC biology, and its potential as a therapeutic target.

Keywords: Clear cell renal cell carcinoma; TPX2; The Cancer Genome Atlas.