Identification of prognostic and therapeutic biomarkers in type 2 papillary renal cell carcinoma.
Biomarker
Prognosis
Type 2 papillary renal cell carcinoma
mTOR inhibitor
Journal
World journal of surgical oncology
ISSN: 1477-7819
Titre abrégé: World J Surg Oncol
Pays: England
ID NLM: 101170544
Informations de publication
Date de publication:
16 Mar 2023
16 Mar 2023
Historique:
received:
26
10
2021
accepted:
08
11
2022
entrez:
17
3
2023
pubmed:
18
3
2023
medline:
21
3
2023
Statut:
epublish
Résumé
Papillary renal cell carcinoma (PRCC) can be divided into type 1 (PRCC1) and type 2 (PRCC2) and PRCC2 share a more invasive phenotype and worse prognosis. This study aims to identify potential prognostic and therapeutic biomarkers in PRCC2. A cohort from The Cancer Genome Atlas and two datasets from Gene Expression Omnibus were examined. Common differentially expressed genes (DEGs) were screened and potential biomarkers were explored by using Kaplan-Meier method and cox regression analysis. Functional enrichment analysis was utilized to evaluate the potential biological functions. Tumor infiltrating immune cells were estimated by CIBERSORT algorithm. Ninety-two PRCC2 samples from Fudan University Shanghai Cancer Center were obtained, and immunostaining was performed to validate prognostic and therapeutic significance of the potential biomarker. PRCC2 has worse overall survival and shares distinct molecular characteristics from PRCC1. There was significant higher expression level of Targeting protein for Xklp2 (TPX2) in PRCC2 compared with normal tissues. Higher expression level of TPX2 was significantly associated with worse overall survival in PRCC2 and kinesin family genes expression were found significantly elevated in high risk PRCC2. Abundance of tumor infiltrating M1 macrophage was significantly higher in PRCC2 and it was also associated with worse overall survival. In the FUSCC cohort, higher TPX2 expression was significantly correlated with worse overall and progression-free survival. Retrospective analysis indicated that mTOR inhibitor (everolimus) had greater efficacy in the high-risk group than in the low-risk group (overall response rate: 28.6% vs. 16.7%) and that everolimus had greater efficacy than sunitinib in the high-risk group (overall response rate: 28.6% vs. 20%). TPX2 was a prognostic and therapeutic biomarker in PRCC2. Higher abundance of tumor infiltrating M1 macrophage was significantly associated with worse overall survival in PRCC2. mTOR inhibitors may have good efficacy in patients with high-risk PRCC2.
Sections du résumé
BACKGROUND
BACKGROUND
Papillary renal cell carcinoma (PRCC) can be divided into type 1 (PRCC1) and type 2 (PRCC2) and PRCC2 share a more invasive phenotype and worse prognosis. This study aims to identify potential prognostic and therapeutic biomarkers in PRCC2.
METHODS
METHODS
A cohort from The Cancer Genome Atlas and two datasets from Gene Expression Omnibus were examined. Common differentially expressed genes (DEGs) were screened and potential biomarkers were explored by using Kaplan-Meier method and cox regression analysis. Functional enrichment analysis was utilized to evaluate the potential biological functions. Tumor infiltrating immune cells were estimated by CIBERSORT algorithm. Ninety-two PRCC2 samples from Fudan University Shanghai Cancer Center were obtained, and immunostaining was performed to validate prognostic and therapeutic significance of the potential biomarker.
RESULTS
RESULTS
PRCC2 has worse overall survival and shares distinct molecular characteristics from PRCC1. There was significant higher expression level of Targeting protein for Xklp2 (TPX2) in PRCC2 compared with normal tissues. Higher expression level of TPX2 was significantly associated with worse overall survival in PRCC2 and kinesin family genes expression were found significantly elevated in high risk PRCC2. Abundance of tumor infiltrating M1 macrophage was significantly higher in PRCC2 and it was also associated with worse overall survival. In the FUSCC cohort, higher TPX2 expression was significantly correlated with worse overall and progression-free survival. Retrospective analysis indicated that mTOR inhibitor (everolimus) had greater efficacy in the high-risk group than in the low-risk group (overall response rate: 28.6% vs. 16.7%) and that everolimus had greater efficacy than sunitinib in the high-risk group (overall response rate: 28.6% vs. 20%).
CONCLUSIONS
CONCLUSIONS
TPX2 was a prognostic and therapeutic biomarker in PRCC2. Higher abundance of tumor infiltrating M1 macrophage was significantly associated with worse overall survival in PRCC2. mTOR inhibitors may have good efficacy in patients with high-risk PRCC2.
Identifiants
pubmed: 36927438
doi: 10.1186/s12957-022-02836-3
pii: 10.1186/s12957-022-02836-3
pmc: PMC10022194
doi:
Substances chimiques
Everolimus
9HW64Q8G6G
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
98Subventions
Organisme : National Key Research and Development Program of China
ID : 2019YFC1316005
Organisme : National Natural Science Foundation of China
ID : 81802525
Organisme : National Natural Science Foundation of China
ID : 81772706
Organisme : National Natural Science Foundation of China
ID : 81902568
Organisme : Shanghai Science and Technology Development Foundation
ID : 20ZR1413100
Organisme : Shanghai Science and Technology Development Foundation
ID : 18511108000
Organisme : Shanghai Sailing Program
ID : 19YF1409700
Informations de copyright
© 2023. The Author(s).
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