title: Phosphorylated 4EBP1 is associated with tumor progression and poor prognosis in Xp11.2 translocation renal cell carcinoma.
abstract: Two main signaling pathways, PI3K-AKT-mTOR and RAS-MAPK, are involved in transmitting the proliferative signals which play critical roles in human cancers. However, the functions of these pathways in Xp11.2 RCC remain undefined. This study aimed to explore the expression of mTOR and MAPK cascades in Xp11.2 RCC and to assess the prognostic significance of proteins evaluated. Immunohistochemistry was performed to evaluate the expression of 4EBP1, p-4EBP1, p-mTOR, p-S6K and p-MAPK in 36 adult Xp11.2 RCC patients who were confirmed by FISH assay. Cox regression models were used to evaluate the prognostic value of all covariates. Among 36 assessed patients, 14 (38.9%), 26 (72.2%), 16 (44.4%), 19 (52.8%), and 9 (25.0%) patients showed high expression of 4EBP1, p-4EBP1, p-mTOR, p-S6K, and p-MAPK, respectively. We noted that p-4EBP1 expression was significantly correlated with lymph node metastases (P = 0.027). Multivariate analysis showed that high p-4EBP1 expression was an independent adverse prognostic factor for both PFS (HR = 33.750, P = 0.017) and OS (HR = 56.111, P = 0.026). Our findings suggest that p-4EBP1 may serve as a funnel factor that converge the upstream proliferative oncogenic signals. Effective inhibition of the pathways responsible for 4E-BP1 phosphorylation might be a useful strategy to improve the outcome of Xp11.2 RCC patients.
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Institute of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Hongkai
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Chang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Dai
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Guohai
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Dingwei
authors.initials: D
authors.lastname: Ye
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018797:Cell Cycle Proteins; D041321:Chromosomes, Human, X / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D011499:Protein Processing, Post-Translational; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins