Prognostic significance of PI3K/AKT/ mTOR signaling pathway members in clear cell renal cell carcinoma

PeerJ

article

Demin Fan¹  Qiang Liu²  Fei Wu¹  Na Liu³  Hongyi Qu⁴  Yijiao Yuan⁴  Yong Li⁵  Huayu Gao⁴  Juntao Ge⁴  Yue Xu⁴  Hao Wang⁴  Qingyong Liu¹  Zuohui Zhao⁴ 

[1] Department of Urology, The First Affiliated Hospital of Shandong First Medical University;Laboratory of Microvascular Medicine, The First Affiliated Hospital of Shandong First Medical University;Department of Hematology, Qilu Hospital of Shandong University;Department of Pediatric Surgery, The First Affiliated Hospital of Shandong First Medical University;Department of Urology, Shandong Yuncheng County Chinese Medicine Hospital

关键词: Clear cell renal cell carcinoma;    Overall survival;    PTEN;    mTOR;    TCPA;   

DOI  :  10.7717/peerj.9261

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundRenal cell carcinoma (RCC) is a fatal disease, in which the PI3K/AKT/mTOR signaling pathway serves an important role in the tumorigenesis. Previous studies have reported the prognostic significance of PI3K/AKT/mTOR signaling pathway members in RCC; however, there is insufficient evidence to date to confirm this. Thus, the present study aimed to systematically investigate the prognostic roles of multiple PI3K/AKT/mTOR signaling proteins in clear cell RCC (ccRCC) using online large-scale databases.MethodsThe mRNA expression profiles of PI3K/AKT/mTOR signaling pathway proteins PTEN, PIK3CA, PIK3CB, PIK3CD, PIK3CG, AKT1, AKT2, AKT3 and mTOR were investigated using the Gene Expression Profiling Interactive Analysis (GEPIA) and Oncomine databases, and the protein expression levels of PI3K, AKT and mTOR were detected using western blotting (WB) analysis. In addition, the correlation between mRNA or protein expression levels and the prognostic significance was analyzed using the Kaplan-Meier (K-M) plotter (n = 530), the Human Protein Atlas (HPA; n = 528) and The Cancer Protein Atlas (TCPA; n = 445) databases.ResultsThe GEPIA revealed that the mRNA expression of major PI3K/AKT/mTOR pathway members, including PTEN, PIK3CA, PIK3CB, AKT1, AKT2 and AKT3, were negatively correlated with ccRCC stages (P < 0.05), though most of their mRNA and protein expression levels were notsignificantly different between ccRCC and normal tissues using GEPIA, Oncomine and WB analyses (P < 0.05). Meanwhile, using the K-M plotter and HPA prognostic analysis, it was found that the mRNA expression levels of the majority of the PI3K/AKT/mTOR signaling pathway members, including PTEN, PIK3CA, PIK3CB, PIK3CG, AKT3 and mTOR were positively correlated with overall survival (OS), whereas PIK3CD mRNA expression was negatively correlated with OS (P < 0.05). Furthermore, TCPA prognostic analysis observed that several of the key molecules of the PI3K/AKT/mTOR signaling pathway [PTEN, p-AKT (S473) and p-mTOR (S2448)] were also positively correlated with OS in patients with ccRCC (P < 0.05). In conclusion, the present study suggested that several members of the PI3K/AKT/mTOR signaling pathway, especially PTEN, may be favorable prognostic factors in ccRCC, which indicated that the PI3K/AKT/mTOR signaling pathway may be implicated in ccRCC initiation and progression.

【 授权许可】

CC BY