Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Clear Cell Renal Cell Carcinoma

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Abstract

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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Genetic associations in diabetic nephropathy: a meta-analysis

A. Mooyaart, E. J. J. Valk, L. A. van Es … (2010)

Aims/hypothesis This meta-analysis assessed the pooled effect of each genetic variant reproducibly associated with diabetic nephropathy. Methods PubMed, EMBASE and Web of Science were searched for articles assessing the association between genes and diabetic nephropathy. All genetic variants statistically associated with diabetic nephropathy in an initial study, then independently reproduced in at least one additional study, were selected. Subsequently, all studies assessing these variants were included. The association between these variants and diabetic nephropathy (defined as macroalbuminuria/proteinuria or end-stage renal disease [ESRD]) was calculated at the allele level and the main measure of effect was a pooled odds ratio. Pre-specified subgroup analyses were performed, stratifying for type 1/type 2 diabetes mellitus, proteinuria/ESRD and ethnic group. Results The literature search yielded 3,455 citations, of which 671 were genetic association studies investigating diabetic nephropathy. We identified 34 replicated genetic variants. Of these, 21 remained significantly associated with diabetic nephropathy in a random-effects meta-analysis. These variants were in or near the following genes: ACE, AKR1B1 (two variants), APOC1, APOE, EPO, NOS3 (two variants), HSPG2, VEGFA, FRMD3 (two variants), CARS (two variants), UNC13B, CPVL and CHN2, and GREM1, plus four variants not near genes. The odds ratios of associated genetic variants ranged from 0.48 to 1.70. Additional variants were detected in subgroup analyses: ELMO1 (Asians), CCR5 (Asians) and CNDP1 (type 2 diabetes). Conclusions/interpretation This meta-analysis found 24 genetic variants associated with diabetic nephropathy. The relative contribution and relevance of the identified genes in the pathogenesis of diabetic nephropathy should be the focus of future studies. Electronic supplementary material The online version of this article (doi:10.1007/s00125-010-1996-1) contains supplementary material, which is available to authorised users.

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Renal cell carcinoma 2005: new frontiers in staging, prognostication and targeted molecular therapy.

John S Lam, Oleg Shvarts, John T Leppert … (2005)

Renal cell carcinoma (RCC) has traditionally been staged using a purely anatomical staging system. Although current staging systems provide good prognostic information, data published in the last few years has led to significant controversies as to whether further revisions are needed and whether improvements can be made with the introduction of new, more accurate and predictive prognostic factors not currently included in traditional staging systems. This review highlights such controversies and provides an update on current staging modalities, prognostic factors and targeted molecular therapy for RCC. A comprehensive review of the peer reviewed literature was performed on the topic of current staging modalities, validated prognostic factors, predictive nomograms, molecular markers and targeted molecular therapy for RCC. A staging system for malignant disease such as RCC uses various characteristics of tumors to stratify patients into clinically meaningful categories, which can be used to provide patients with counseling regarding prognosis, select treatment modalities and determine eligibility for clinical trials. The TNM staging system is currently the most extensively used one. However, it has undergone recent systematic revision due to rapidly emerging data from longer patient followup. The identification of various histological and symptomatic factors has led groups at many centers to develop more comprehensive staging systems that integrate these factors and include patients with metastatic and local disease. While integrated staging systems have improved RCC staging, the recent discovery of molecular tumor markers is expected to revolutionize RCC staging in the future and lead to the development of new therapies based on molecular targeting. Staging systems for RCC serve as a valuable prognostic tool. Several new patient and tumor characteristics have been reported to be important prognostic factors and they have been integrated into current staging systems. In addition, the field of RCC is rapidly undergoing a revolution led by molecular markers and targeted therapies. With this information urologists will be updated with the most current and comprehensive staging strategies, and be provided with a glimpse of the molecular and patient specific staging and treatment paradigms that will in our opinion transform the future management of this malignancy.

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Apolipoprotein C1: Its Pleiotropic Effects in Lipid Metabolism and Beyond

Elena V Fuior, Anca Gafencu (2019)

Apolipoprotein C1 (apoC1), the smallest of all apolipoproteins, participates in lipid transport and metabolism. In humans, APOC1 gene is in linkage disequilibrium with APOE gene on chromosome 19, a proximity that spurred its investigation. Apolipoprotein C1 associates with triglyceride-rich lipoproteins and HDL and exchanges between lipoprotein classes. These interactions occur via amphipathic helix motifs, as demonstrated by biophysical studies on the wild-type polypeptide and representative mutants. Apolipoprotein C1 acts on lipoprotein receptors by inhibiting binding mediated by apolipoprotein E, and modulating the activities of several enzymes. Thus, apoC1 downregulates lipoprotein lipase, hepatic lipase, phospholipase A2, cholesterylester transfer protein, and activates lecithin-cholesterol acyl transferase. By controlling the plasma levels of lipids, apoC1 relates directly to cardiovascular physiology, but its activity extends beyond, to inflammation and immunity, sepsis, diabetes, cancer, viral infectivity, and—not last—to cognition. Such correlations were established based on studies using transgenic mice, associated in the recent years with GWAS, transcriptomic and proteomic analyses. The presence of a duplicate gene, pseudogene APOC1P, stimulated evolutionary studies and more recently, the regulatory properties of the corresponding non-coding RNA are steadily emerging. Nonetheless, this prototypical apolipoprotein is still underexplored and deserves further research for understanding its physiology and exploiting its therapeutic potential.

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Author and article information

Contributors

Yankang Cui: URI : http://loop.frontiersin.org/people/869020/overview

Chenkui Miao: URI : http://loop.frontiersin.org/people/1055046/overview

Chao Hou: URI : http://loop.frontiersin.org/people/1055040/overview

Zengjun Wang: URI : http://loop.frontiersin.org/people/724745/overview

Bianjiang Liu: URI : http://loop.frontiersin.org/people/831666/overview

Journal

Journal ID (nlm-ta): Front Oncol

Journal ID (iso-abbrev): Front Oncol

Journal ID (publisher-id): Front. Oncol.

Title: Frontiers in Oncology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 2234-943X

Publication date (Electronic): 20 August 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 1436

Affiliations

Department of Urology, The First Affiliated Hospital of Nanjing Medical University , Nanjing, China

Author notes

Edited by: Xin Xu, Zhejiang University, China

Reviewed by: Jonas Busch, Charité–Universitätsmedizin Berlin, Germany; Matteo Ferro, European Institute of Oncology (IEO), Italy

*Correspondence: Bianjiang Liu bjliu@ 123456njmu.edu.cn

This article was submitted to Genitourinary Oncology, a section of the journal Frontiers in Oncology

†These authors have contributed equally to this work

Article

DOI: 10.3389/fonc.2020.01436

PMC ID: 7468425

PubMed ID: 32974161

SO-VID: c939a535-7e11-4271-9a71-1b47e1d3f513

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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 15 February 2020

Date accepted : 07 July 2020

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Figures: 6, Tables: 2, Equations: 0, References: 25, Pages: 9, Words: 4681

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Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Clear Cell Renal Cell Carcinoma

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Karger: Oncology

Most cited references 20

Genetic associations in diabetic nephropathy: a meta-analysis

Renal cell carcinoma 2005: new frontiers in staging, prognostication and targeted molecular therapy.

Apolipoprotein C1: Its Pleiotropic Effects in Lipid Metabolism and Beyond

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Cited by 15

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