CancerGeneNet: linking driver genes to cancer hallmarks

Iannuccelli, Marta; Micarelli, Elisa; Surdo, Prisca Lo; Palma, Alessandro; Perfetto, Livia; Rozzo, Ilaria; Castagnoli, Luisa; Licata, Luana

doi:10.1093/nar/gkz871

Cited by 34 publications

(43 citation statements)

References 26 publications

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“…Studies reporting on molecular/genetic data of GEP MiNENs have identified well-characterised carcinogenetic hallmarks of more common GEP malignancies as potential drivers of this disease, such as alterations affecting TP53, KRAS, BRAF, APC, PI3KCA, and MSI [102], corroborating what was previously reported by Girardi D.M. et al [10]; these alterations are usually shared between the two components and likely present in founding clones.…”

Section: Discussionsupporting

confidence: 83%

Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: A Systematic Review of a Controversial and Underestimated Diagnosis

Frizziero

Chakrabarty

Nagy

et al. 2020

JCM

140

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Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) represent a rare diagnosis of the gastro-entero-pancreatic tract. Evidence from the current literature regarding their epidemiology, biology, and management is of variable quality and conflicting. Based on available data, the MiNEN has an aggressive biological behaviour, mostly driven by its (often high-grade) neuroendocrine component, and a dismal prognosis. In most cases, the non-neuroendocrine component is of adenocarcinoma histology. Due to limitations in diagnostic methods and poor awareness within the scientific community, the incidence of MiNENs may be underestimated. In the absence of data from clinical trials, MiNENs are commonly treated according to the standard of care for pure neuroendocrine carcinomas or adenocarcinomas from the same sites of origin, based on the assumption of a biological similarity to their pure counterparts. However, little is known about the molecular aberrations of MiNENs, and their pathogenesis remains controversial; molecular/genetic studies conducted so far point towards a common monoclonal origin of the two components. In addition, mutations in tumour-associated genes, including TP53, BRAF, and KRAS, and microsatellite instability have emerged as potential drivers of MiNENs. This systematic review (91 full manuscripts or abstracts in English language) summarises the current reported literature on clinical, pathological, survival, and molecular/genetic data on MiNENs.

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Section: Discussionsupporting

confidence: 83%

Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: A Systematic Review of a Controversial and Underestimated Diagnosis

Frizziero

Chakrabarty

Nagy

et al. 2020

JCM

140

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“…Another way to analyze the correlation between hypoxia and metastasis was unrevealing the shortest paths from hypoxia-related proteins to metastasis signaling 62 . We found that 99 of 233 (42%) proteins had paths to metastasis where 49 had positive regulation with an average distance of 3.0, and 16 had negative regulation with an average distance of 3.5.…”

Section: Discussionmentioning

confidence: 99%

“…We analyzed the 233 hypoxia-related proteins by using CancerGeneNet software in order to find the shortest paths to metastasis according to Iannuccelli et al 62 (Table S30). Additionally, 27 (12%) of them presented a frequency mean of genomic alterations more than the average (> 0.068) across 17 TCGA Pan-Cancer types (Table S1).…”

Section: Shortest Paths From Hypoxia-related Proteins To Metastasismentioning

confidence: 99%

“…This resource is based on the annotation of experimental information that permits to embed the cancer genes into the cell network of causal protein relationships curated in SIGNOR 78 . Consequently, this bioinformatics tool allows to infer likely paths of causal interactions linking cancer associated genes to cancer phenotypes such as metastasis 62 . Iannuccelli et al explained that the shortest paths between a specific gene and cancer phenotypes was programmatically implemented using the shortest path function of the R igraph, obtaining a distance score and a path length score 62,79 .…”

Section: Shortest Paths From Hypoxia-related Proteins To Metastasismentioning

confidence: 99%

“…Consequently, this bioinformatics tool allows to infer likely paths of causal interactions linking cancer associated genes to cancer phenotypes such as metastasis 62 . Iannuccelli et al explained that the shortest paths between a specific gene and cancer phenotypes was programmatically implemented using the shortest path function of the R igraph, obtaining a distance score and a path length score 62,79 . Hence, we analyzed the shortest paths from our hypoxia-related proteins to metastasis to better understand the association to this hallmark of cancer 62,80 .…”

Section: Shortest Paths From Hypoxia-related Proteins To Metastasismentioning

confidence: 99%

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Metastatic signaling of hypoxia-related genes across TCGA Pan-Cancer types

López‐Cortés

Guevara-Ramírez

Guerrero

et al. 2020

Preprint

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Many primary-tumor subregions have low levels of molecular oxygen, termed hypoxia.Hypoxic tumors are at elevated risk for local failure and distant metastasis. Metastatic disease is the leading cause of cancer-related deaths and involves critical interactions between tumor cells and the microenvironment. Here we focused on elucidating the molecular hallmarks of tumor hypoxia that remains poorly defined. To fill this gap, we analyzed the genomic alterations and hypoxia score of 233 hypoxia-related genes of 6,343 individuals across 17 TCGA Pan-Cancer types. In addition, we analyzed a protein-protein interactome (PPi) network and the shortest paths from hypoxic proteins to metastasis. As results, mRNA high alteration was prevalent in all cancer types. Genomic alterations and hypoxia score presented a highest frequency in tumor stage 4 and positive metastasis status in all cancer types. The most significant signaling pathways were HIF-1, ErbB, PI3K-Akt, FoxO, mTOR, Ras and VEGF. The PPi network revealed a strong association among hypoxic proteins, cancer driver proteins and metastasis driver proteins. The analysis of shortest paths revealed 99 ways to spread metastasis signaling from hypoxic proteins. Additionally, we proposed 62 hypoxic genes strongly associated with metastasis and 27 of them with high amount of genomic alterations. Overall, tumor hypoxia may drive aggressive molecular features across cancer types. Hence, we identified potential biomarkers and therapeutic targets regulated by hypoxia that could be incorporated into strategies aimed at improving novel drug development and treating metastasis.

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Hepatogenesis and hepatocarcinogenesis: Alignment of the main signaling pathways

Shokouhian

Negahdari

et al. 2022

Journal Cellular Physiology

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Development is a symphony of cells differentiation in which different signaling pathways are orchestrated at specific times and periods to form mature and functional cells from undifferentiated cells. The similarity of the gene expression profile in malignant and undifferentiated cells is an interesting topic that has been proposed for many years and gave rise to the differentiation-therapy concept, which appears a rational insight and should be reconsidered. Hepatocellular carcinoma (HCC), as the sixth common cancer and the third leading cause of cancer death worldwide, is one of the health-threatening complications in communities where hepatotropic viruses are endemic. Sedentary lifestyle and high intake of calories are other risk factors. HCC is a complex condition in which various dimensions must be addressed, including heterogeneity of cells in the tumor mass, high invasiveness, and underlying diseases that limit the treatment options. Under these restrictions, recognizing, and targeting common signaling pathways during liver development and HCC could expedite to a rational therapeutic approach, reprograming malignant cells to well-differentiated ones in a functional state. Accordingly, in this review, we

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CancerGeneNet: linking driver genes to cancer hallmarks

Cited by 34 publications

References 26 publications

Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: A Systematic Review of a Controversial and Underestimated Diagnosis

Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: A Systematic Review of a Controversial and Underestimated Diagnosis

Metastatic signaling of hypoxia-related genes across TCGA Pan-Cancer types

Hepatogenesis and hepatocarcinogenesis: Alignment of the main signaling pathways

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