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Correlation between hyaluronic acid,hyaluronic Acid synthase and human renal clear cell carcinoma.

ABSTRACT: OBJECTIVE:To study the correlation between hyaluronic acid (HA), hyaluronic acid synthase (HAS) and human renal clear cell carcinoma (RCCC). METHODS:The expression of three HAS isoforms' gene and HA in 93 RCCC tissues, 27 nephridial tissues by the side of RCCC from two hospitals were measured with Real-Time RT-PCR?Western Blot and immunohistochemical methods and analyzed. RESULTS:All RCCC and adjacent normal tissues expressed three HASs' mRNA & protein; at the mRNA level, both RCCC and adjacent normal tissues, expressed more HAS3 than HAS1 or HAS2, their differences were statistically significant (all P values <0.05); but, at the protein level, all HAS isoforms presented the equivalent expression. Compared with the adjacent non-neoplastic kidney tissues, the expression of all HAS isoforms' mRNA in RCCC tissues were increased evidently and their differences were significant (all P values <0.0001); but at the protein level, only the expression of HAS3 increased evidently (P=0.022). In all adjacent normal tissues, more than 80% renal tubular cells strongly expressed HA, however, only the minority RCCC cases (16/93) presented weakly positive HA staining in few cancer nests (5%-30%), the difference were significant (P<0.0001). In RCCC tissues subgrouped according to clinical stage, pathological grade, lymphatic metastasis or not and distant metastasis or not, the HASs' mRNA & protein differential expression all had no statistical significance (all P values >0.05). CONCLUSION:Different from other malignancy, HA and HASs (except for HAS3) may not play important roles in the biological progress of human RCCC.

SUBMITTER: Cai JL

PROVIDER: S-EPMC3587526 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Correlation between hyaluronic acid,hyaluronic Acid synthase and human renal clear cell carcinoma.

Cai Jian-Liang JL Li Ming M Na Yan-Qun YQ

Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 20110301 1

<h4>Objective</h4>To study the correlation between hyaluronic acid (HA), hyaluronic acid synthase (HAS) and human renal clear cell carcinoma (RCCC).<h4>Methods</h4>The expression of three HAS isoforms' gene and HA in 93 RCCC tissues, 27 nephridial tissues by the side of RCCC from two hospitals were measured with Real-Time RT-PCR、Western Blot and immunohistochemical methods and analyzed.<h4>Results</h4>All RCCC and adjacent normal tissues expressed three HASs' mRNA & protein; at the mRNA level, b ...[more]

PMID: 23467480

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Project description:Purpose: Lipid metabolism reprogramming is a major pathway in tumor evolution. This study investigated fatty acid synthase (FASN) mRNA expression in anthropometric adipose tissue and elucidated the prognostic value and potential mechanism of clear cell renal cell carcinoma (ccRCC). Materials and Methods: Transcription profiles were obtained from 533 ccRCC samples in The Cancer Genome Atlas (TCGA) cohorts. Real-time quantitative PCR (RT-qPCR) and immunohistochemistry were performed to detect FASN expression in 380 paired ccRCC and normal tissues from the Fudan University Shanghai Cancer Center (FUSCC). Visceral adipose tissue (VAT) and subcutaneous adipose tissue were at the level of the umbilicus as measured by magnetic resonance imaging (MRI). Non-targeted metabolomics and in vitro experiments were used to reveal the biological functions of FASN. Results: Increased FASN expression was significantly relevant to advanced T, N, and American Joint Committee on Cancer (AJCC) stages (p < 0.01) and significantly correlated to poor progression-free survival (PFS) and overall survival (OS) of 913 ccRCC patients in FUSCC and TCGA cohorts. Pearson's correlation coefficient indicated that FASN amplification was positively correlated to VAT% (r = 0.772, p < 0.001), which significantly correlated to poor PFS (HR = 2.066, p = 0.028) and OS (HR = 2.773, p = 0.023) in the FUSCC cohort. Transient inhibition or overexpression of FASN significantly regulated A498 and 786O cell proliferation and migration by regulating epithelial-mesenchymal transition. Inhibition of FASN led to a higher apoptotic rate and decreased lipid droplet formation compared with normal control in ccRCC cells. Non-targeted metabolomics showed that decreased de novo lipogenesis might be required to sustain an elevation of glycolytic activity in 786O cells by regulating galactinol, dl-lactate, N-acetylaspartylglutamate, and sucrose, thereby participating in carcinogenesis and progression of ccRCC. Conclusion: This study demonstrated that FASN expression is positively related to aggressive cell proliferation, migration, apoptosis, and lipid droplet formation and regulates metabolic disorders of the ccRCC microenvironment. Additionally, elevated FASN mRNA expression is significantly correlated to the abdominal obesity distribution, especially VAT%, which is a significant predictor of a poor prognosis for ccRCC patients.

Dataset Information

Correlation between hyaluronic acid,hyaluronic Acid synthase and human renal clear cell carcinoma.

Publications

Correlation between hyaluronic acid,hyaluronic Acid synthase and human renal clear cell carcinoma.

Similar Datasets

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