THSD7A expression: a novel immunohistochemical determinant in predicting overall survival of metastatic renal cell carcinoma treated with targeted therapy.

ABSTRACT

BACKGROUND: The association of thrombospondin type 1 domain-containing 7A (THSD7A) expression, a novel angiogenesis-related marker, with survival outcomes of tumors including renal cell carcinoma (RCC) remains to be clarified. Therefore, we investigated the impact of THSD7A on outcomes of metastatic RCC (mRCC) patients treated with targeted therapy. METHODS: A total of 86 mRCC patients were included. The expression of THSD7A in nephrectomy material of the patients was assessed by immunohistochemistry and expression patterns were categorized into two groups negative (no staining) and positive. Univariable and multivariable Cox regression models evaluated the impact of THSD7A expression on progression free survival (PFS) and overall survival (OS) of the patients. RESULTS: THSD7A expression was determined in 77.9% of the patients. Kaplan-Meier analyses showed that while the patients with THSD7A expression had significantly inferior OS times than those with negative THSD7A expression (19.9 months vs. 52.2 months, P = 0.024, respectively), there was no association between THSD7A expression and PFS. The univariate analyses demonstrated that the significant variables in predicting OS were presence of bone metastasis (P = 0.030), THSD7A expression (P = 0.028), and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) scoring system (P < 0.001). However, applying multivariate analyses, the independent variables in predicting OS were THSD7A expression (HR 2.639, P = 0.037) and IMDC scoring system (P < 0.001). CONCLUSION: We revealed that THSD7A expression was associated with OS of mRCC patients treated with targeted therapy. There might be an important link between THSD7A expression and resistance to targeted therapy.