Integrative omics analysis reveals relationships of genes with synthetic lethal interactions through a pan-cancer analysis

Guo, Li; Li, Sunjing; Qian, Bowen; Wang, Youquan; Duan, Rui; Jiang, Wenwen; Kang, Yihao; Dou, Yuyang; Yang, Guowei; Shen, Lulu; Wang, Jun; Liang, Tingming

doi:10.1016/j.csbj.2020.10.015

Cited by 4 publications

(3 citation statements)

References 56 publications

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“…Next generation DNA sequencing (NGS) has brought about revolution in genomic research. In the literature, numerous reports can be found proposing comprehensive and novel molecular pathophysiological, diagnostic, therapeutic and prognostic genes associated with ACC [ 4 , 50 , 113 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 ]. Zheng et al have summarized proposed genes as potential drivers involved in sporadic adrenocortical tumorigenesis, including insulin-like growth factor 2, β-catenin (CTNNB1), TP53, ZNRF3 and TERT, as well as novel nominated drivers such as PRKAR1A, RPL22, TERF2, CCNE1 and NF1 [ 161 ].…”

Section: Genetic Analysismentioning

confidence: 99%

The Role of Biomarkers in Adrenocortical Carcinoma: A Review of Current Evidence and Future Perspectives

2021

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Adrenocortical carcinoma (ACC) is a rare endocrine malignancy arising from the adrenal cortex often with unexpected biological behavior. It can occur at any age, with two peaks of incidence: in the first and between fifth and seventh decades of life. Although ACC are mostly hormonally active, precursors and metabolites, rather than end products of steroidogenesis are produced by dedifferentiated and immature malignant cells. Distinguishing the etiology of adrenal mass, between benign adenomas, which are quite frequent in general population, and malignant carcinomas with dismal prognosis is often unfeasible. Even after pathohistological analysis, diagnosis of adrenocortical carcinomas is not always straightforward and represents a great challenge for experienced and multidisciplinary expert teams. No single imaging method, hormonal work-up or immunohistochemical labelling can definitively prove the diagnosis of ACC. Over several decades’ great efforts have been made in finding novel reliable and available diagnostic and prognostic factors including steroid metabolome profiling or target gene identification. Despite these achievements, the 5-year mortality rate still accounts for approximately 75% to 90%, ACC is frequently diagnosed in advanced stages and therapeutic options are unfortunately limited. Therefore, imperative is to identify new biological markers that can predict patient prognosis and provide new therapeutic options.

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Section: Genetic Analysismentioning

confidence: 99%

The Role of Biomarkers in Adrenocortical Carcinoma: A Review of Current Evidence and Future Perspectives

2021

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“…We recently proposed that synthetic lethality, a well-established concept in cancer therapy (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11), could mitigate multiple known shortcomings of current antiviral drugs such as the paucity of options, restricted target spectrum due to the small genome size of viruses, the often rapid development of drug resistance (12), marginal effectiveness due to dose-limiting toxicity (13), and the necessity to redesign drugs as new viral strains emerge (14,15). Of 92 approved antiviral drugs in 2018, two-thirds were aimed at HIV and HCV and almost 90% were small molecule drugs (16,17).…”

Section: Introductionmentioning

confidence: 99%

Predicting host-based, synthetic lethal antiviral targets from omics data

Staheli,

Neal,

Navare

et al. 2023

Preprint

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Traditional antiviral therapies often have limited effectiveness due to toxicity and development of drug resistance. Host-based antivirals, while an alternative, may lead to non-specific effects. Recent evidence shows that virus-infected cells can be selectively eliminated by targeting synthetic lethal (SL) partners of proteins disrupted by viral infection. Thus, we hypothesized that genes depleted in CRISPR KO screens of virus-infected cells may be enriched in SL partners of proteins altered by infection. To investigate this, we established a computational pipeline predicting SL drug targets of viral infections. First, we identified SARS-CoV-2-induced changes in gene products via a large compendium of omics data. Second, we identified SL partners for each altered gene product. Last, we screened CRISPR KO data for SL partners required for cell viability in infected cells. Despite differences in virus-induced alterations detected by various omics data, they share many predicted SL targets, with significant enrichment in CRISPR KO-depleted datasets. Comparing data from SARS-CoV-2 and influenza infections, we found possible broad-spectrum, host-based antiviral SL targets. This suggests that CRISPR KO data are replete with common antiviral targets due to their SL relationship with virus-altered states and that such targets can be revealed from analysis of omics datasets and SL predictions.

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“…Multi-omics datasets, generated from clinical specimens and shared via different platforms by global researchers, include transcriptomics, genetics/epigenetics, proteomics, metabolomics, and single cell RNA-seq [8][9][10]. The online resources make it possible to look into any particular gene of interest in our research field.…”

Section: Introductionmentioning

confidence: 99%

Omics Overview of the SPARC Gene in Mesothelioma

Perrot

2023

Biomolecules

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The SPARC gene plays multiple roles in extracellular matrix synthesis and cell shaping, associated with tumor cell migration, invasion, and metastasis. The SPARC gene is also involved in the epithelial-mesenchymal transition (EMT) process, which is a critical phenomenon leading to a more aggressive cancer cell phenotype. SPARC gene overexpression has shown to be associated with poor survival in the mesothelioma (MESO) cohort from the TCGA database, indicating that this gene may be a powerful prognostic factor in MESO. Its overexpression is correlated with the immunosuppressive tumor microenvironment. Here, we summarize the omics advances of the SPARC gene, including the summary of SPARC gene expression associated with prognosis in pancancer and MESO, the immunosuppressive microenvironment, and cancer cell stemness. In addition, SPARC might be targeted by microRNAs. Notably, despite the controversial functions on angiogenesis, SPARC may directly or indirectly contribute to tumor angiogenesis in MESO. In conclusion, SPARC is involved in tumor invasion, metastasis, immunosuppression, cancer cell stemness, and tumor angiogenesis, eventually impacting patient survival. Strategies targeting this gene may provide novel therapeutic approaches to the treatment of MESO.

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Integrative omics analysis reveals relationships of genes with synthetic lethal interactions through a pan-cancer analysis

Abstract: Graphical abstract

Cited by 4 publications

References 56 publications

The Role of Biomarkers in Adrenocortical Carcinoma: A Review of Current Evidence and Future Perspectives

The Role of Biomarkers in Adrenocortical Carcinoma: A Review of Current Evidence and Future Perspectives

Predicting host-based, synthetic lethal antiviral targets from omics data

Omics Overview of the SPARC Gene in Mesothelioma

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