Whole Exome and Transcriptome RNA-Sequencing Model for the Diagnosis of Prostate Cancer

Nikas, Jason B.; Mitanis, Nikos T; Nikas, Emily G.

doi:10.1021/acsomega.9b02995

Cited by 10 publications

(11 citation statements)

References 21 publications

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“…Among these biomarkers, only MKLN1-AS has been reported in HCC and is considered a diagnostic and prognostic biomarker (42). HPN-AS1 could be utilized in the diagnosis of prostate cancer (43); LINC00607 facilitates the proliferation and invasion of osteosarcoma (44); USP2-AS1 promotes the progression of colon cancer and ovarian cancer (45,46); and LINC00638 and LINC00652 have been reported in nontumor diseases (47)(48)(49)(50), while no study has revealed the function of the remaining lncRNAs. As a result, further exploration of these lncRNAs may improve insight into the molecules underlying HCC.…”

Section: Discussionmentioning

confidence: 99%

Tumor Mutation Burden-Associated LINC00638/miR-4732-3p/ULBP1 Axis Promotes Immune Escape via PD-L1 in Hepatocellular Carcinoma

Feng

Zhao

et al. 2021

Front. Oncol.

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Tumor mutation burden (TMB) is associated with immune infiltration, while its underlying mechanism in hepatocellular carcinoma (HCC) remains unclear. A long noncoding RNA (lncRNA)-related competitive endogenous RNA (ceRNA) network can regulate various tumor behaviors, and research about its correlation with TMB and immune infiltration is warranted. Data were downloaded from TCGA and ArrayExpress databases. Cox analysis and machine learning algorithms were employed to establish a lncRNA-based prognostic model for HCC. We then developed a nomogram model to predict overall survival and odds of death for HCC patients. The association of this prognostic model with TMB and immune infiltration was also analyzed. In addition, a ceRNA network was constructed by using DIANA-LncBasev2 and the starBase database and verified by luciferase reporter and colocalization analysis. Multiplex immunofluorescence was applied to determine the correlation between ULBP1 and PD-L1. An eight-lncRNA (SLC25A30-AS1, HPN-AS1, LINC00607, USP2-AS1, HCG20, LINC00638, MKLN1-AS and LINC00652) prognostic score model was constructed for HCC, which was highly associated with TMB and immune infiltration. Next, we constructed a ceRNA network, LINC00638/miR-4732-3p/ULBP1, that may be responsible for NK cell infiltration in HCC with high TMB. However, patients with high ULBP1 possessed a poorer prognosis. Using multiplex immunofluorescence, we found a significant correlation between ULBP1 and PD-L1 in HCC, and patients with high ULBP1 and PD-L1 had the worst prognosis. In brief, the eight-lncRNA model is a reliable tool to predict the prognosis of HCC patients. The LINC00638/miR-4732-3p/ULBP1 axis may regulate immune escape via PD-L1 in HCC with high TMB.

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Section: Discussionmentioning

confidence: 99%

Tumor Mutation Burden-Associated LINC00638/miR-4732-3p/ULBP1 Axis Promotes Immune Escape via PD-L1 in Hepatocellular Carcinoma

Feng

Zhao

et al. 2021

Front. Oncol.

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“…We further assessed significant methylation-gene expression associations identified in blood tissue analyses in adjacent normal prostate tissue of PrCa patients in the TCGA (N = 34). The processing of DNA methylation and gene expression data has been described elsewhere 62,63 .…”

Section: Methodsmentioning

confidence: 99%

An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk

Yang

Guo

et al. 2020

Nat Commun

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It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for CpG sites associated with PrCa risk, here we establish genetic models to predict methylation (N = 1,595) and conduct association analyses with PrCa risk (79,194 cases and 61,112 controls). We identify 759 CpG sites showing an association, including 15 located at novel loci. Among those 759 CpG sites, methylation of 42 is associated with expression of 28 adjacent genes. Among 22 genes, 18 show an association with PrCa risk. Overall, 25 CpG sites show consistent association directions for the methylation-gene expression-PrCa pathway. We identify DNA methylation biomarkers associated with PrCa, and our findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes.

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“…The most relevant gene was MED29, a component of the Mediator complex that is involved in the regulation of transcription [31]. MED29 has been related to prostate cancer [48].…”

Section: Discussionmentioning

confidence: 99%

High Expression of Caspase-8 Associated with Improved Survival in Diffuse Large B-Cell Lymphoma: Machine Learning and Artificial Neural Networks Analyses

et al. 2021

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High expression of the anti-apoptotic TNFAIP8 is associated with poor survival of the patients with diffuse large B-cell lymphoma (DLBCL), and one of the functions of TNFAIP8 is to inhibit the pro-apoptosis Caspase-8. We aimed to analyze the immunohistochemical expression of Caspase-8 (active subunit p18; CASP8) in a series of 97 cases of DLBCL from Tokai University Hospital, and to correlate with other Caspase-8 pathway-related markers, including cleaved Caspase-3, cleaved PARP, BCL2, TP53, MDM2, MYC, Ki67, E2F1, CDK6, MYB and LMO2. After digital image quantification, the correlation with several clinicopathological characteristics of the patients showed that high protein expression of Caspase-8 was associated with a favorable overall and progression-free survival (Hazard Risks = 0.3; p = 0.005 and 0.03, respectively). Caspase-8 also positively correlated with cCASP3, MDM2, E2F1, TNFAIP8, BCL2 and Ki67. Next, the Caspase-8 protein expression was modeled using predictive analytics, and a high overall predictive accuracy (>80%) was obtained with CHAID decision tree, Bayesian network, discriminant analysis, C5 tree, logistic regression, and Artificial Intelligence Neural Network methods (both Multilayer perceptron and Radial basis function); the most relevant markers were cCASP3, E2F1, TP53, cPARP, MDM2, BCL2 and TNFAIP8. Finally, the CASP8 gene expression was also successfully modeled in an independent DLBCL series of 414 cases from the Lymphoma/Leukemia Molecular Profiling Project (LLMPP). In conclusion, high protein expression of Caspase-8 is associated with a favorable prognosis of DLBCL. Predictive modeling is a feasible analytic strategy that results in a solution that can be understood (i.e., explainable artificial intelligence, “white-box” algorithms).

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Whole Exome and Transcriptome RNA-Sequencing Model for the Diagnosis of Prostate Cancer

Cited by 10 publications

References 21 publications

Tumor Mutation Burden-Associated LINC00638/miR-4732-3p/ULBP1 Axis Promotes Immune Escape via PD-L1 in Hepatocellular Carcinoma

Tumor Mutation Burden-Associated LINC00638/miR-4732-3p/ULBP1 Axis Promotes Immune Escape via PD-L1 in Hepatocellular Carcinoma

An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk

High Expression of Caspase-8 Associated with Improved Survival in Diffuse Large B-Cell Lymphoma: Machine Learning and Artificial Neural Networks Analyses

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