TY - JOUR
T1 - Proteomic analysis of chromophobe renal cell carcinoma and benign renal oncocytoma biopsies reveals shared metabolic dysregulation
AU - Carvalho, Luís B.
AU - Jorge, Susana
AU - López-Fernández, Hugo
AU - Lodeiro, Carlos
AU - Dhir, Rajiv
AU - Campos Pinheiro, Luís
AU - Medeiros, Mariana
AU - Santos, Hugo M.
AU - Capelo, José L.
N1 - info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50006%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0008%2F2020/PT#
info:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F144222%2F2019/PT#
info:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F120537%2F2016/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0008%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50006%2F2020/PT#
Funding Information:
The PROTEOMASS Scientific Society (Portugal) is acknowledged for the funding provided through the General Funding Grant 2022-2023 and by the funding provided to the Laboratory for Biological Mass Spectrometry Isabel Moura (#PM001/2019 and #PM003/2016). HLF is supported by a ‘María Zambrano’ postdoctoral contract from Ministerio de Universidades (Gobierno de España). This project benefited from the University of Pittsburgh Hillman Cancer Center shared resource facility (Cancer Genomics Facility) supported in part by award P30CA047904.
Funding Information:
This work received support from the PROTEOMASS Scientific Society through the General Funding Grant 2022–2023 and the projects #PM001/2019 and #PM003/2016.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/11/28
Y1 - 2023/11/28
N2 - Background: This study investigates the proteomic landscapes of chromophobe renal cell carcinoma (chRCC) and renal oncocytomas (RO), two subtypes of renal cell carcinoma that together account for approximately 10% of all renal tumors. Despite their histological similarities and shared origins, chRCC is a malignant tumor necessitating aggressive intervention, while RO, a benign growth, is often subject to overtreatment due to difficulties in accurate differentiation. Methods: We conducted a label-free quantitative proteomic analysis on solid biopsies of chRCC (n = 5), RO (n = 5), and normal adjacent tissue (NAT, n = 5). The quantitative analysis was carried out by comparing protein abundances between tumor and NAT specimens. Our analysis identified a total of 1610 proteins across all samples, with 1379 (85.7%) of these proteins quantified in at least seven out of ten LC‒MS/MS runs for one renal tissue type (chRCC, RO, or NAT). Results: Our findings revealed significant similarities in the dysregulation of key metabolic pathways, including carbohydrate, lipid, and amino acid metabolism, in both chRCC and RO. Compared to NAT, both chRCC and RO showed a marked downregulation in gluconeogenesis proteins, but a significant upregulation of proteins integral to the citrate cycle. Interestingly, we observed a distinct divergence in the oxidative phosphorylation pathway, with RO showing a significant increase in the number and degree of alterations in proteins, surpassing that observed in chRCC. Conclusions: This study underscores the value of integrating high-resolution mass spectrometry protein quantification to effectively characterize and differentiate the proteomic landscapes of solid tumor biopsies diagnosed as chRCC and RO. The insights gained from this research offer valuable information for enhancing our understanding of these conditions and may aid in the development of improved diagnostic and therapeutic strategies.
AB - Background: This study investigates the proteomic landscapes of chromophobe renal cell carcinoma (chRCC) and renal oncocytomas (RO), two subtypes of renal cell carcinoma that together account for approximately 10% of all renal tumors. Despite their histological similarities and shared origins, chRCC is a malignant tumor necessitating aggressive intervention, while RO, a benign growth, is often subject to overtreatment due to difficulties in accurate differentiation. Methods: We conducted a label-free quantitative proteomic analysis on solid biopsies of chRCC (n = 5), RO (n = 5), and normal adjacent tissue (NAT, n = 5). The quantitative analysis was carried out by comparing protein abundances between tumor and NAT specimens. Our analysis identified a total of 1610 proteins across all samples, with 1379 (85.7%) of these proteins quantified in at least seven out of ten LC‒MS/MS runs for one renal tissue type (chRCC, RO, or NAT). Results: Our findings revealed significant similarities in the dysregulation of key metabolic pathways, including carbohydrate, lipid, and amino acid metabolism, in both chRCC and RO. Compared to NAT, both chRCC and RO showed a marked downregulation in gluconeogenesis proteins, but a significant upregulation of proteins integral to the citrate cycle. Interestingly, we observed a distinct divergence in the oxidative phosphorylation pathway, with RO showing a significant increase in the number and degree of alterations in proteins, surpassing that observed in chRCC. Conclusions: This study underscores the value of integrating high-resolution mass spectrometry protein quantification to effectively characterize and differentiate the proteomic landscapes of solid tumor biopsies diagnosed as chRCC and RO. The insights gained from this research offer valuable information for enhancing our understanding of these conditions and may aid in the development of improved diagnostic and therapeutic strategies.
KW - Chromophobe Renal Cell Carcinoma
KW - Label-free Quantification
KW - Mass Spectrometry
KW - OCT-embedded tissues
KW - Renal Oncocytoma
KW - Total Protein Approach
UR - http://www.scopus.com/inward/record.url?scp=85178060653&partnerID=8YFLogxK
U2 - 10.1186/s12014-023-09443-8
DO - 10.1186/s12014-023-09443-8
M3 - Article
C2 - 38017382
AN - SCOPUS:85178060653
SN - 1542-6416
VL - 20
JO - Clinical Proteomics
JF - Clinical Proteomics
IS - 1
M1 - 54
ER -
