Dataset Information

EVI1 as a Prognostic and Predictive Biomarker of Clear Cell Renal Cell Carcinoma.

ABSTRACT: The transcription factor EVI1 plays an oncogenic role in several types of neoplasms by promoting aggressive cancer features. EVI1 contributes to epigenetic regulation and transcriptional control, and its overexpression has been associated with enhanced PI3K-AKT-mTOR signaling in some settings. These observations raise the possibility that EVI1 influences the prognosis and everolimus-based therapy outcome of clear cell renal cell carcinoma (ccRCC). Here, gene expression and protein immunohistochemical studies of ccRCC show that EVI1 overexpression is associated with advanced disease features and with poorer outcome-particularly in the CC-e.3 subtype defined by The Cancer Genome Atlas. Overexpression of an oncogenic EVI1 isoform in RCC cell lines confers substantial resistance to everolimus. The EVI1 rs1344555 genetic variant is associated with poorer survival and greater progression of metastatic ccRCC patients treated with everolimus. This study leads us to propose that evaluation of EVI1 protein or gene expression, and of EVI1 genetic variants may help improve estimates of prognosis and the benefit of everolimus-based therapy in ccRCC.

SUBMITTER: Palomero L

PROVIDER: S-EPMC7072453 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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EVI1 as a Prognostic and Predictive Biomarker of Clear Cell Renal Cell Carcinoma.

Palomero Luis L Bodnar Lubomir L Mateo Francesca F Herranz-Ors Carmen C Espín Roderic R García-Varelo Mar M Jesiotr Marzena M Ruiz de Garibay Gorka G Casanovas Oriol O López José I JI Pujana Miquel Angel MA

Cancers 20200128 2

The transcription factor EVI1 plays an oncogenic role in several types of neoplasms by promoting aggressive cancer features. EVI1 contributes to epigenetic regulation and transcriptional control, and its overexpression has been associated with enhanced PI3K-AKT-mTOR signaling in some settings. These observations raise the possibility that EVI1 influences the prognosis and everolimus-based therapy outcome of clear cell renal cell carcinoma (ccRCC). Here, gene expression and protein immunohistoche ...[more]

PMID: 32012804

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Project description:BackgroundTumor Protein D52-Like 2 (TPD52L2) is a tumor-associated protein that participates in B-cell differentiation. However, the role of TPD52L2 in the pathological process of clear cell renal cell carcinoma (ccRCC) is unclear.MethodsMultiple omics data of ccRCC samples were obtained from public databases, and 5 pairs of ccRCC tissue samples were collected from the operating room. Wilcox, chi-square test, Kaplan-Meier method, receiver operating characteristic curve, regression analysis, meta-analysis, and correlation analysis were used to clarify the relationship of TPD52L2 with clinical features, prognosis, and immune microenvironment. Functional enrichment analysis was performed to reveal the potential pathways in which TPD52L2 participates in the progression of ccRCC. The siRNA technique was used to knockdown in the expression level of TPD52L2 in 786-O cells to verify its effect on ccRCC progression.ResultsFirst, TPD52L2 was found to be upregulated in ccRCC at both mRNA and protein levels. Second, TPD52L2 was significantly associated with poor prognosis and served as an independent prognostic factor. Moreover, TPD52L2 expression was regulated by DNA methylation, and some methylation sites were associated with ccRCC prognosis. Third, TPD52L2 overexpression may participate in the pathological process through various signaling pathways such as cytokine-cytokine receptor interactions, PI3K-Akt, IL-17, Wnt, Hippo signaling pathway, and ECM-receptor interactions. Interestingly, TPD52L2 expression level was also closely related to the abundance of various immune cells, immune checkpoint expression, and TMB. Finally, in vitro experiments confirmed that knocking down TPD52L2 can inhibit the proliferation, migration, and invasion abilities of ccRCC cells.ConclusionThis study for the first time revealed the upregulation of TPD52L2 expression in ccRCC, which is closely associated with poor prognosis of patients and is a potentially valuable therapeutic and efficacy assessment target for immunotherapy.

Project description:Background: Apolipoprotein C1 (APOC1) has been proved to play a critical role in gastric, breast, lung, and pancreatic cancer. However, the relationship between APOC1 and urinary tumors remains unclear. This study aimed to assess the diagnostic and prognostic value of APOC1 in urinary tumors. Methods: We performed a pan analysis of APOC1 mRNA expression in urinary cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) database. To further investigate the prognostic value of APOC1 expression in urinary cancers, the Kaplan-Meier plotter database was used. Furthermore, we collected the tumor and adjacent normal samples of 32 ccRCC patients to perform qRT-PCR and western blotting assays. A total of 72 cases with ccRCC were analyzed using tissue microarrays (TMAs). Results: Our results based on Kaplan-Meier plotter database indicated that a high expression of APOC1 may lead to poor overall survival (OS, p = 0.0019) in patients with ccRCC. Furthermore, the cancer stages and tumor grade of ccRCC appeared to be strongly linked with APOC1 expression according to UALCAN database. Hence, we reached a preliminary conclusion that APOC1 may play a key role in the tumorigenesis and progression of ccRCC. Furthermore, the Kaplan-Meier survival curve analyses of 72 clinical patients indicated that high expression of APOC1 was associated with poor progression-free survival (PFS, p = 0.007) and OS (p = 0.022). In addition, univariate Cox regression analysis confirmed the significant relationship between APOC1 expression and survival (p = 0.038). The TMAs analysis in combination with the patients' clinicopathological features was also performed. The expression of APOC1 was found to be significantly correlated with the tumor size (p = 0.018) and histological grade (p = 0.016). Conclusions: In conclusion, the findings of our study suggest that APOC1 may serve as a novel diagnostic and prognostic biomarker for ccRCC. Further evidence on the mechanism of APOC1 promoting tumor progression may transform it to a new therapeutic target for the treatment of ccRCC.

Dataset Information

EVI1 as a Prognostic and Predictive Biomarker of Clear Cell Renal Cell Carcinoma.

Publications

EVI1 as a Prognostic and Predictive Biomarker of Clear Cell Renal Cell Carcinoma.

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