Overexpression of phosphatidylinositol 4-kinase type IIIα is associated with undifferentiated status and poor prognosis of human hepatocellular carcinoma

Ilboudo, Adeodat; Nault, Jean–Charles; Dubois-Pot-Schneider, Hélène; Corlu, Anne; Zucman‐Rossi, Jessica; Samson, Michel; Seyec, Jacques Le

doi:10.1186/1471-2407-14-7

Cited by 22 publications

(16 citation statements)

References 32 publications

(40 reference statements)

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“…Phosphatidylinositol 4-Kinase Alpha ( PI4KA ) catalyzes the first step of the biosynthesis of phosphatidylinositol 4,5-bisphosphate. It has been found to be overexpressed in hepatocarcinoma, showing a positive and significant correlation with expression of PCNA and KI67 proliferation markers and associated to a poor prognosis [41] . HECT Domain And RCC1-Like Domain-Containing Protein 2 ( HERC2 ) facilitates the assembly of the RNF8-UBC13 complex to recruit BRCA1 to DNA damaged sites, and it also plays a role in p53 oligomerization [42] .…”

Section: Discussionmentioning

confidence: 99%

Mutations, Differential Gene Expression, and Chimeric Transcripts in Esophageal Squamous Cell Carcinoma Show High Heterogeneity

Souza-Santos

Lima

Nicolau-Neto

et al. 2018

Translational Oncology

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Esophageal squamous cell carcinoma (ESCC) is a frequent and lethal neoplasia. As recent advances in targeted therapy have not improved ESCC prognosis, characterization of molecular alterations associated to this tumor is of foremost relevance. In this study, we analyze, for the first time, the complete genomic profile of ESCC by RNA-seq. TP53 was the most frequently mutated gene in the investigation and validation sets (78.6% and 67.4%, respectively). Differential expression analysis between tumor and nontumor adjacent mucosa showed 6698 differentially expressed genes, most of which were overexpressed (74%). Enrichment analysis identified overrepresentation of Wnt pathway, with overexpressed activators and underexpressed inactivators, suggesting activation of canonical and noncanonical Wnt signaling pathways. Higher WNT7B expression was associated with poor prognosis. Twenty-one gene fusions were identified in 50% of tumors, none of which involving the same genes in different patients; 71% of fusions involved syntenic genes. Comparisons with TCGA data showed co-amplification of seven gene pairs involved in fusions in the present study (~33%), suggesting that these rearrangements might have been driven by chromoanagenesis. In conclusion, genomic alterations in ESCC are highly heterogeneous, impacting negatively in target therapy development.

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Section: Discussionmentioning

confidence: 99%

Mutations, Differential Gene Expression, and Chimeric Transcripts in Esophageal Squamous Cell Carcinoma Show High Heterogeneity

Souza-Santos

Lima

Nicolau-Neto

et al. 2018

Translational Oncology

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“…All 40 genes, however, did not affect prognosis in patients with TP53 mutant cancer (Figure 6B , Supplementary Figure 1 ), demonstrating a dependence on TP53 mutational status. The genes selected using this method included NCOA3 [ 34 , 35 ], HOXA1 [ 36 ], FOLR1 [ 37 ], SOCS1 [ 38 ], and PIK4CA [ 39 ], which showed similar expression patterns related to survival in patients with cancer. This result suggested that our method was a relatively simple method for identification of genes functionally associated with the p53 pathway.…”

Section: Discussionmentioning

confidence: 99%

A novel isolation method for cancer prognostic factors via the p53 pathway by a combination of in vitro and in silico analyses

Kamijo

Kawahara

Yoshinaga³

et al. 2018

Oncoscience

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Identifying new therapeutic target genes affecting the survival of patients with cancer is crucial for the development of new cancer therapies. Here, we developed a novel technology combining in vitro short hairpin RNA (shRNA) library screening and in silico analysis of the tumor transcriptome to identify prognostic factors via the p53 tumor-suppressor pathway. For initial screening, we screened 5,000 genes through selection of shRNAs in p53 wild-type tumor cells that altered sensitivity to the p53 activator actinomycin D (ActD) to identify p53 regulatory genes; shRNAs targeting 322 genes were obtained. Among these 322 genes, seven were prognostic factor candidates whose high expression increased ActD sensitivity while prolonging the survival period in patients with the p53 wild-type genotype. Conversely, we identified 33 genes as prognostic factor candidates among ActD-resistant genes related to a shortened survival period only in p53 wild-type tumors. These 40 genes had biological functions such as apoptosis, drug response, cell cycle checkpoint, and cell proliferation. The 40 genes selected by this method contained many known genes related to the p53 pathway and prognosis in patients with cancer. In summary, we developed an efficient screening method to identify p53-dependent prognostic factors with in vitro experimental data and database analysis.

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“…The similarity ratios for PIK3CA and PI4KA were nearly equal to those for PTEN. Dysregulation of PIK3CA and PI4KA is commonly found in HNSCC [46] and hepatocellular carcinoma [43], respectively.…”

Section: Detecting One-hit Oncogenementioning

confidence: 99%

Oncogene inference optimization using constraint-based modelling incorporated with protein expression in normal and tumour tissues

Shu

et al. 2020

R. Soc. open sci.

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Cancer cells are known to exhibit unusual metabolic activity, and yet few metabolic cancer driver genes are known. Genetic alterations and epigenetic modifications of cancer cells result in the abnormal regulation of cellular metabolic pathways that are different when compared with normal cells. Such a metabolic reprogramming can be simulated using constraint-based modelling approaches towards predicting oncogenes. We introduced the tri-level optimization problem to use the metabolic reprogramming towards inferring oncogenes. The algorithm incorporated Recon 2.2 network with the Human Protein Atlas to reconstruct genome-scale metabolic network models of the tissue-specific cells at normal and cancer states, respectively. Such reconstructed models were applied to build the templates of the metabolic reprogramming between normal and cancer cell metabolism. The inference optimization problem was formulated to use the templates as a measure towards predicting oncogenes. The nested hybrid differential evolution algorithm was applied to solve the problem to overcome solving difficulty for transferring the inner optimization problem into the single one. Head and neck squamous cells were applied as a case study to evaluate the algorithm. We detected 13 of the top-ranked one-hit dysregulations and 17 of the top-ranked two-hit oncogenes with high similarity ratios to the templates. According to the literature survey, most inferred oncogenes are consistent with the observation in various tissues. Furthermore, the inferred oncogenes were highly connected with the TP53/AKT/IGF/MTOR signalling pathway through PTEN, which is one of the most frequently detected tumour suppressor genes in human cancer.

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Overexpression of phosphatidylinositol 4-kinase type IIIα is associated with undifferentiated status and poor prognosis of human hepatocellular carcinoma

Cited by 22 publications

References 32 publications

Mutations, Differential Gene Expression, and Chimeric Transcripts in Esophageal Squamous Cell Carcinoma Show High Heterogeneity

Mutations, Differential Gene Expression, and Chimeric Transcripts in Esophageal Squamous Cell Carcinoma Show High Heterogeneity

A novel isolation method for cancer prognostic factors via the p53 pathway by a combination of in vitro and in silico analyses

Oncogene inference optimization using constraint-based modelling incorporated with protein expression in normal and tumour tissues

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