Expression of Glycolysis-Related Proteins in Cancer of Unknown Primary Origin

Author(s)

Bonatelli, Murilo ^[1] ; Fornari, Isabella Fernandes ^{[1, 2]} ; Bernecule, Priscila Neves ^{[1, 2]} ; Pinheiro, Lara Esquiapatti ^{[1, 2]} ; Costa, Ricardo Filipe Alves ^{[2, 3]} ; Longatto-Filho, Adhemar ^{[4, 1, 5, 6]} ; Junior, Joao Neif Antonio ^[7] ; Silva, Eduardo Caetano Albino ^[8] ; Carcano, Flavio Mavignier ^{[2, 7]} ; Pinheiro, Celine ^{[1, 2]}

Affiliation

^[1] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos - Brazil

^[2] Dr Paulo Prata FACISB, Barretos Sch Hlth Sci, Barretos - Brazil

^[3] Barretos Canc Hosp, Res & Teaching Inst, Barretos - Brazil

^[4] ICVS 3Bs PT Govt Associate Lab, Braga - Portugal

^[5] Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga - Portugal

^[6] Univ Sao Paulo, Sch Med, Lab Med Invest LIM14, Sao Paulo - Brazil

^[7] Barretos Canc Hosp, Med Oncol Dept, Barretos - Brazil

^[8] Barretos Canc Hosp, Pathol Dept, Barretos - Brazil

• Document type: Journal article
• Source: FRONTIERS IN ONCOLOGY; v. 11, JUN 24 2021.
• Web of Science Citations: 0

Abstract

Introduction Cancer of unknown primary origin (CUP) is defined as metastatic cancer without identification of the primary site. Considering that only 15-20% of patients with CUP show a favorable outcome, identifying biomarkers may help improve the clinical management of patients who do not respond well to conventional therapies. In this context, the study of the metabolic profile of CUP may pave the way to establish new biomarkers and/or therapeutic targets; therefore, this study aimed to characterize the expression of metabolism-related proteins in CUP. Materials and Methods The expression of monocarboxylate transporters MCT1, MCT2 and MCT4, their chaperone CD147, the glucose transporter GLUT1 and the pH regulator CAIX was evaluated by immunohistochemistry in a series of 118 CUP patients, and the results were associated with the available clinicopathological information. Results The metabolism-related proteins MCT1, MCT4, CD147, GLUT1 and CAIX were expressed in a critical portion of the CUP (approximately 20 to 70%). MCT1 and CD147 were both more frequently expressed in cases with lymph nodes as metastasis dominant sites (p = 0.001) as well as in samples from lymph nodes (p <0.001 and p = 0.002, respectively), while MCT1 expression was more frequently expressed in squamous cell carcinomas (p = 0.045). A higher overall survival was observed in patients with tumors positive for GLUT1 and CAIX expression (p = 0.011 and p = 0.041, respectively), but none of the proteins was an independent prognostic factor for overall survival in multivariable analysis. Conclusion The results suggest that a portion of CUPs present a hyperglycolytic phenotype, which is associated with higher overall survival. (AU)

• FAPESP's process: 17/09226-2 - Characterization of MCT1 and MCT2 expression in tumors of unknown primary site
• Grantee: Lara Esquiapatti Pinheiro
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 16/08674-9 - Characterization of GLUT1 and CAIX expression in carcinoma of unknown primary
• Grantee: Priscila Neves Bernécule
• Support Opportunities: Scholarships in Brazil - Scientific Initiation