TRAP1 protein signature predicts outcome in human metastatic colorectal carcinoma.
TRAP1 is a HSP90 molecular chaperone upregulated in colorectal carcinomas and involved in control of intracellular signaling, cell cycle, apoptosis and drug resistance, stemness and bioenergetics through co-traslational regulation of a network of client proteins. Thus, the clinical significance of TRAP1 protein network was analyzed in human colorectal cancers. TRAP1 and/or its client proteins were quantified, by immunoblot analysis, in 60 surgical specimens of colorectal carcinomas at different stages and, by immunohistochemistry, in 9 colorectal adenomatous polyps, 11 in situ carcinomas and 55 metastatic colorectal tumors. TRAP1 is upregulated at the transition between low- and high-grade adenomas, in in situ carcinomas and in about 60% of human colorectal carcinomas, being downregulated only in a small cohort of tumors. The analysis of TCGA database showed that a subgroup of colorectal tumors is characterized by gain/loss of TRAP1 copy number, this correlating with its mRNA and protein expression. Interestingly, TRAP1 is co-expressed with the majority of its client proteins and hierarchical cluster analysis showed that the upregulation of TRAP1 and associated 6-protein signature (i.e., IF2α, eF1A, TBP7, MAD2, CDK1 and βCatenin) identifies a cohort of metastatic colorectal carcinomas with a significantly shorter overall survival (HR 5.4; 95% C.I. 1.1-26.6; p=0.037). Consistently, the prognostic relevance of TRAP1 was confirmed in a cohort of 55 metastatic colorectal tumors. Finally, TRAP1 positive expression and its prognostic value are more evident in left colon cancers. These data suggest that TRAP1 protein network may provide a prognostic signature in human metastatic colorectal carcinomas.
Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy.
Francesca
F
Maddalena
Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy.
Vittorio
V
Simeon
Pathology, IRCCS, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy.
Giulia
G
Vita
Medical Oncology Units, IRCCS, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy.
Annamaria
A
Bochicchio
Pathology, IRCCS, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy.
Luciana
L
Possidente
Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy.
Lorenza
L
Sisinni
Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy.
Giacomo
G
Lettini
Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy.
Valentina
V
Condelli
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.
Danilo Swann
DS
Matassa
Medical Oncology, Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy.
Valeria
V
Li Bergolis
General Surgery Units, Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy.
Alberto
A
Fersini
Medical Oncology, Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy.
Sante
S
Romito
Medical Oncology Units, IRCCS, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy.
Michele
M
Aieta
General Surgery Units, Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy.
Antonio
A
Ambrosi
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.
Franca
F
Esposito
Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy.|Medical Oncology, Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy.
Matteo
M
Landriscina
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D018628:Gene Dosage; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D059467:Transcriptome; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D018841:HSP90 Heat-Shock Proteins; C092306:TRAP1 protein, human
TRAP1; client proteins; colorectal carcinoma; overall survival; protein signature