Discordant Protein- and Transcript-Level Expression of TRAF7 and the EDA2R–Apoptotic Axis in Clear Cell Renal Cell Carcinoma

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is characterized by dysregulated apoptotic and inflammatory signaling, yet the tissue-level behavior of several candidate regulators remains poorly defined. Materials and Methods: We quantified ectodysplasin A2 receptor (EDA2R), TNF-receptor-associated factor 7 (TRAF7) and the apoptotic fragments cleaved-PARP1 and cleaved-CASP3 by immunofluorescence in 49 ccRCC and 27 matched non-tumoral cortex samples and analyzed the corresponding transcripts in TCGA-KIRC and GTEx. Results: TRAF7 protein was higher in tumor than in control tissue (median 0.81% vs. 0.63% positive area, p = 0.015), an increase concentrated in grade 2–3 tumors, whereas EDA2R and the apoptotic fragments did not differ (all p > 0.59). The positive EDA2R–cleaved-PARP1 correlation in low-grade tumors (ρ = +0.54, p = 0.002) was attenuated in high-grade tumors (ρ = +0.06, p = 0.84). In TCGA-KIRC, EDA2R mRNA was overexpressed in tumors, and higher expression was associated with better overall survival (HR = 0.60, p = 0.0011), including after mutual adjustment for the four transcripts (HR = 0.66, p = 5.3 × 10−5) and after adjustment for age, sex, stage and grade (HR per standard deviation = 0.83, p = 0.008). TRAF7 mRNA did not differ between tumor and normal tissue, but higher levels were associated with worse overall survival after the same adjustment (HR = 1.38, p < 0.001). Conclusions: TRAF7 and EDA2R show opposite, marker-specific discordance between protein- and transcript-level data across cohorts, consistent with, but not demonstrating, regulation beyond transcription. EDA2R is a candidate transcript-level prognostic marker requiring validation, and TRAF7 is a protein-level feature of ccRCC; paired RNA–protein and functional studies are needed.