Eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) is phosphorylated and activated by mammalian target of rapamycin complex 1, which serves as a regulator of cell growth, cell survival, metastasis and angiogenesis in many types of cancer. The aim of this study was to evaluate the role of phosphorylated 4EBP1 (p4EBP1) in primary renal cell carcinoma (RCC) as a biomarker in metastatic RCC (mRCC) and non-mRCC cohorts. Primary tumor tissue from 254 non-mRCC and 60 mRCC patients were immunohistochemically stained for t4EBP1 and p4EBP1. The disease-free interval (DFI) categorized by the expressions and clinical parameters were assessed by univariate and multivariate analysis in the non-mRCC cohort. Then, the cause-specific survival (CSS) was assessed in the mRCC cohort by the same methods as used in the non-mRCC cohort. In the non-mRCC cohort, patients with t4EBP1 expression had no RCC recurrence. Patients with p4EBP1 expression had the shorter DFI in univariate analysis (P=0.037). p4EBP1 and pT1b-4 expression levels were independent predictors for de novo metastasis. In the mRCC cohort, intermediate/poor MSKCC risk, non-clear cell RCC, and no p4EBP1 expression were correlated with poor CSS on multivariate analysis. Expression of p4EBP1 could be a predictive biomarker for de novo metastasis in non-mRCC patient cohort. By contrast, mRCC patients showing no p4EBP1 expression had shorter CSS than patients with p4EBP1 expression.
Oncology letters. 2019 Feb 12 [Epub]
Sei Naito, Osamu Ichiyanagi, Hiromi Ito, Takanobu Kabasawa, Hidenori Kanno, Takafumi Narisawa, Hiroki Fukuhara, Mayu Yagi, Yuta Kurota, Atsushi Yamagishi, Toshihiko Sakurai, Hayato Nishida, Hisashi Kawazoe, Takuya Yamanobe, Tomoyuki Kato, Peter Makhov, Vladimir M Kolenko, Mitsunori Yamakawa, Norihiko Tsuchiya
Department of Urology, Yamagata University Faculty of Medicine, Yamagata, Yamagata 990-9585, Japan., Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Yamagata 990-9585, Japan., Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.