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

Mgbemena

et al. 2020

Cancers

Published transcriptomic data from surgically removed metastatic clear cell renal cell carcinoma samples were analyzed from the genomic fabric paradigm (GFP) perspective to identify the best targets for gene therapy. GFP considers the transcriptome as a multi-dimensional mathematical object constrained by a dynamic set of expression controls and correlations among genes. Every gene in the chest wall metastasis, two distinct cancer nodules, and the surrounding normal tissue of the right kidney was characterized by three independent measures: average expression level, relative expression variation, and expression correlation with each other gene. The analyses determined the cancer-induced regulation, control, and remodeling of the chemokine and vascular endothelial growth factor (VEGF) signaling, apoptosis, basal transcription factors, cell cycle, oxidative phosphorylation, renal cell carcinoma, and RNA polymerase pathways. Interestingly, the three cancer regions exhibited different transcriptomic organization, suggesting that the gene therapy should not be personalized only for every patient but also for each major cancer nodule. The gene hierarchy was established on the basis of gene commanding height, and the gene master regulators DAPK3,TASOR, FAM27C and ALG13 were identified in each profiled region. We delineated the molecular mechanisms by which TASOR overexpression and ALG13 silencing would selectively affect the cancer cells with little consequences for the normal cells.

Section: Discussionmentioning

confidence: 99%

Genomic Fabric Remodeling in Metastatic Clear Cell Renal Cell Carcinoma (ccRCC): A New Paradigm and Proposal for a Personalized Gene Therapy Approach

Mgbemena

et al. 2020

Cancers

“…There are numerous (1,459 listed in PubMed [62]) studies using microarray data to identify altered gene expression profiles and biomarkers in ccRCC nodules with respect to normal counterparts (among the most recent [63][64][65]). One may ask: How are these findings a departure from other studies?…”

Section: Discussionmentioning

confidence: 99%

Genomic Fabric Remodeling in Metastatic Clear Cell Renal Cell Carcinoma (ccRCC): A New Paradigm and Proposal for a Personalized Gene Therapy Approach

Mgbemena

et al. 2020

Preprint

Published transcriptomic data from surgically removed metastatic clear cell renal cell carcinoma (ccRCC) samples were re-analyzed from the Genomic Fabric Perspective that considers the transcriptome a multi-dimensional mathematical object, constrained by a dynamic set of expression correlations among genes. Every gene in the chest wall metastasis (MET), two primary tumors (PTA, PTB) and the surrounding normal tissue (NOR) of the right kidney was characterized by three independent measures: average expression level (AVE), relative expression variation (REV) and expression correlation (COR) with each other gene. AVE was used to determine the regulation of the genomic fabrics of ccRCC, apoptosis, chemokine and VEGF signaling pathways. REV quantified the alteration of the transcripts’ abundances control, while COR determined the remodeling of the transcriptomic networks of chemokine signaling and oxidative phosphorylation genes. The gene hierarchy was established in based on Gene Commanding Height and the Gene Master Regulators (GMR) TASOR (PTA), FAM27C (PTB) and ALG13 (MET) and DAPK3 (NOR) were identified in each profiled region. We predict that TASOR overexpression would block transcription in PTA but not in PTB, while slightly stimulating it in NOR. Silencing of ALG3 would slow-down the cell-cycle in all three cancer regions with practically no effect in NOR.

“…Cox regression analysis suggested that APOC1 expression remained as an independent prognostic factor for OS of ccRCC patients. A recent study by Cui et al revealed that high expression of APOC1 was correlated with shorter overall survival ( P =0.022) and progression-free survival ( P =0.007), and APOC1 may serve as a novel diagnostic biomarker for ccRCC [ 16 ]. Besides ccRCC, high expression of APOC1 has been found in CRC, and APOC1 overexpression contributed to the poor prognosis of CRC patients [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…A previous study speculated that APOC1 may act as a tumor promoter by regulating cholesterol metabolism, and APOC1 might play a key role in the tumorigenesis and progression of ccRCC [ 16 ]. A study by Li et al indicated that APOC1 acts as a novel pro-metastatic factor, which facilitated the activation of STAT3 and enhanced the metastasis of ccRCC cells [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Apolipoprotein C1 (APOC1) in Clear Cell Renal Cell Carcinoma and Its Prognostic Significance

Xiao

2020

Med Sci Monit

Background The aims of this study included 3 aspects: 1) assessing the expression of Apolipoprotein C1 (APOC1) in clear cell renal cell carcinoma (ccRCC) and normal groups; 2) evaluating the prognostic significance of APOC1 expression in the overall survival (OS) of ccRCC patients; and 3) exploring APOC1-related signaling pathways. Material/Methods The APOC1 expression value and clinical data of ccRCC patients were obtained from the cBioPortal database. We then evaluated the association of APOC1 expression with clinical characteristics of ccRCC patients. We also assessed the correlation between APOC1 expression and clinical outcome using Kaplan-Meier method. Our work then verified the independent prognostic factors of ccRCC by Cox regression analysis. Finally, the potential role of genes co-expressed with APOC1 was revealed via functional enrichment analysis. Results Bioinformatic data revealed that APOC1 was expressed at higher levels in ccRCC tissue than in the normal group (all P <0.05). The high expression of APOC1 was associated with unfavorable prognosis of female patients ( P <0.01), but not of male patients. APOC1 high expression also shortened the survival time of ccRCC patients age ≥60 years old ( P <0.05). Cox regression analysis further indicated that APOC1 expression was an independent prognostic factor for OS of ccRCC patients. Additionally, we found that APOC1 expression was significantly associated with sex, grade, clinical stage, and T stage. Finally, enrichment analysis suggested that APOC1-associated pathways were involved in tumor growth and metastasis. Conclusions The current study indicated that APOC1 was highly expressed in ccRCC and was significantly associated with key clinical features. APOC1 appears to be an independent prognostic factor in patients with ccRCC. Importantly, APOC1 might be a potential therapeutic target for ccRCC via regulating pathways involved in cell growth and metastasis.