Accurate prediction of the prognosis of RCC using a single biomarker is challenging due to the genetic heterogeneity of the disease. However, it is essential to develop an accurate system to allow better patient selection for optimal treatment strategies. ARL4C, ECT2, SOD2, and STEAP3 are novel molecular biomarkers identified in earlier studies as survival-related genes by comprehensive analyses of 43 primary RCC tissues and RCC cell lines.
To develop a prognostic model based on these multiple biomarkers, the expression of four biomarkers ARL4C, ECT2, SOD2, and STEAP3 in primary RCC tissue were semi-quantitatively investigated by immunohistochemical analysis in an independent cohort of 97 patients who underwent nephrectomy, and the clinical significance of these biomarkers were analyzed by survival analysis using Kaplan-Meier curves. The prognostic model was constructed by calculation of the contribution score to prognosis of each biomarker on Cox regression analysis, and its prognostic performance was validated.
Patients whose tumors had high expression of the individual biomarkers had shorter cancer-specific survival (CSS) from the time of primary nephrectomy. The prognostic model based on four biomarkers segregated the patients into a high- and low-risk scored group according to defined cut-off value. This approach was more robust in predicting CSS compared to each single biomarker alone in the total of 97 patients with RCC. Especially in the 36 metastatic RCC patients, our prognostic model could more accurately predict early events within 2 years of diagnosis of metastasis. In addition, high risk-scored patients with particular strong SOD2 expression had a much worse prognosis in 25 patients with metastatic RCC who were treated with molecular targeting agents.
Our findings indicate that a prognostic model based on four novel biomarkers provides valuable data for prediction of clinical prognosis and useful information for considering the follow-up conditions and therapeutic strategies for patients with primary and metastatic RCC.
World journal of surgical oncology. 2020 Oct 22*** epublish ***
Shigehisa Kubota, Tetsuya Yoshida, Susumu Kageyama, Takahiro Isono, Takeshi Yuasa, Junji Yonese, Ryoji Kushima, Akihiro Kawauchi, Tokuhiro Chano
Department of Urology, Shiga University of Medical Science, SetaTshukinowa-cho, Otsu, Shiga, 520-2192, Japan., Central Research Laboratory, Shiga University of Medical Science, SetaTshukinowa-cho, Otsu, Shiga, 520-2192, Japan., Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Koto, Tokyo, 135-8550, Japan., Department of Clinical Laboratory Medicine, Shiga University of Medical Science, SetaTshukinowa-cho, Otsu, Shiga, 520-2192, Japan., Department of Clinical Laboratory Medicine, Shiga University of Medical Science, SetaTshukinowa-cho, Otsu, Shiga, 520-2192, Japan. .