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PPAR? gene is a diagnostic and prognostic biomarker in clear cell renal cell carcinoma by integrated bioinformatics analysis.

ABSTRACT: Genetic alterations in lipid metabolism genes are correlated with progression and poor prognosis of Clear cell renal cell carcinoma (ccRCC). PPAR? play a critical role in lipid metabolism. This study aimed to identify that PPAR? is a diagnosis and prognostic biomarker in ccRCC by integrated bioinformatics analysis. UALCAN database was used to explore the differential expression status and prognostic value of PPAR? gene in various tumor types, qRT-PCR and immunohistochemical staining experiments were utilized for validation. Next, ccRCC data were obtained from TCGA. Correlation between PPAR? expression levels and patients' clinicopathological characteristics was assessed, and the clinically diagnosis and prognostic value of PPAR? were explored in ccRCC. According to the gene set enrichment analysis (GSEA) analysis, PPAR? gene associated biological pathways were identified. PPAR? has prognostic significance only in ccRCC tumors. Expression of PPAR? was associated with ccRCC stages. PPAR? was significantly down-regulated in ccRCC and associated with survival. Gender, tumor dimension, grade and stage showed a significant relevance with PPAR? expression. Lower PPAR? expression revealed significantly poorer survival and progression compared with higher PPAR? expression. Adjusted by other clinical risk factors, PPAR? remained an independent prognostic factor. Moreover, Low PPAR? expression was a potential diagnostic biomarker of ccRCC. A nomogram was constructed based on PPAR? expression and other clinicopathological risk factors, and it performed well in predict patients survival. GSEA analysis showed that PPAR? gene associated biological pathways were enriched in mTOR pathway, AKT pathway, IGF1-mTOR pathway and Wnt signaling pathways. In conclusion, PPAR? expression was decreased in ccRCC tumors. Lower expression of PPAR? is closely correlated with poorer survival. It can be used as a clinically diagnosis and prognostic biomarker in ccRCC.

SUBMITTER: Luo Y

PROVIDER: S-EPMC6584416 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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PPARα gene is a diagnostic and prognostic biomarker in clear cell renal cell carcinoma by integrated bioinformatics analysis.

Luo Yongwen Y Chen Liang L Wang Gang G Qian Guofeng G Liu Xuefeng X Xiao Yu Y Wang Xinghuan X Qian Kaiyu K

Journal of Cancer 20190522 10

Genetic alterations in lipid metabolism genes are correlated with progression and poor prognosis of Clear cell renal cell carcinoma (ccRCC). PPARα play a critical role in lipid metabolism. This study aimed to identify that PPARα is a diagnosis and prognostic biomarker in ccRCC by integrated bioinformatics analysis. UALCAN database was used to explore the differential expression status and prognostic value of PPARα gene in various tumor types, qRT-PCR and immunohistochemical staining experiments ...[more]

PMID: 31258735

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Project description:Background and Objectives: Calcium-binding protein 39-like (CAB39L) has been reported to be downregulated and possessed diagnostic and prognostic values in several types of cancer. However, the clinical value and mechanism of CAB39L in kidney renal clear cell carcinoma (KIRC) remain unclear. Materials and Methods: Bioinformatics analysis was conducted using different databases including TCGA, UALCAN, GEPIA, LinkedOmics, STRING, and TIMER. One-way variance analysis and t-test were chosen to investigate the statistical differences of CAB39L expression in KIRC tissues with different clinical characteristics. The receiver operating characteristic (ROC) curve was chosen to assess the discriminatory capacity of CAB39L. Kaplan-Meier curves were employed for assessing the influence of CAB39L on the progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) of KIRC patients. The independent prognostic significance of clinical parameters for OS such as CAB39L expression in KIRC patients was estimated by Cox analysis. A series of in vitro functional experiments and Western blot (WB) and immunohistochemistry (IHC) were used to validate the relative protein expression and function of CAB39L. Results: The mRNA and protein levels of CAB39L were relatively downregulated in KIRC samples. Meanwhile, hypermethylation of the CAB39L promoter region was possibly associated with its low expression in KIRC. The ROC curve showed that the mRNA expression of CAB39L had a strong diagnostic value for both early and late KIRC. Kaplan-Meier survival curves indicated that a higher mRNA level of CAB39L predicted good PFS, DSS, and OS. The mRNA expression of CAB39L was an independent prognostic factor (hazard ratio = 0.6, p = 0.034) identified by multivariate Cox regression analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis exhibited that CAB39L was mainly associated with substance and energy metabolism. Finally, overexpression of CAB39L impaired the proliferation and metastasis of KIRC cells in vitro. Conclusions: CAB39L possesses prognostic and diagnostic capacity in KIRC.

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.

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Dataset Information

PPAR? gene is a diagnostic and prognostic biomarker in clear cell renal cell carcinoma by integrated bioinformatics analysis.

Publications

PPARα gene is a diagnostic and prognostic biomarker in clear cell renal cell carcinoma by integrated bioinformatics analysis.

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