Our results show that: i) TRAP1 upregulation occurs at the transition between low- and high-grade adenomatous polyps, ii) human CRCs with high TRAP1 levels show a concomitant upregulation of TRAP1 client proteins network; iii) the upregulation of TRAP1 and its protein network predicts poor prognosis in mCRC, and iv) TRAP1 prognostic value is prevalent in left colon carcinomas. The gene discussed is TRAP1; the disease is colon carcinoma.