Challenges and Experiences Extending the cBioPortal for Cancer Genomics to a Molecular Tumor Board Platform

Reimer, Niklas; Unberath, Philipp; Busch, Hauke; Börries, Melanie; Metzger, Patrick Bastos; Ustjanzew, Arsenij; Renner, Christopher; Prokosch, Hans‐Ulrich; Christoph, Jan

doi:10.3233/shti210833

Cited by 12 publications

(11 citation statements)

References 8 publications

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“…Hence, we speculate that ATF6 and PERK may constitute another potential pathway regulated by AGR2 that influences cancer cell progression and resistance to sorafenib. We used the cBioPortal software for Cancer Genomics developed by the Memorial Sloan Kettering Cancer Center (MSKCC) [40][41][42]. AGR2 expression has been demonstrated to be negatively correlated with ATF6 expression (Spearman: − 0.19, p value: 2.15e-4) based on the TCGA, Filehorse microarray dataset.…”

Section: Discussionmentioning

confidence: 99%

Anterior gradient 2 induces resistance to sorafenib via endoplasmic reticulum stress regulation in hepatocellular carcinoma

et al. 2023

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Background Hepatocellular carcinoma (HCC) accounts for almost 80% of all liver cancer cases and is the sixth most common cancer and the second most common cause of cancer-related death worldwide. The survival rate of sorafenib-treated advanced HCC patients is still unsatisfactory. Unfortunately, no useful biomarkers have been verified to predict sorafenib efficacy in HCC. Results We assessed a sorafenib resistance-related microarray dataset and found that anterior gradient 2 (AGR2) is highly associated with overall and recurrence-free survival and with several clinical parameters in HCC. However, the mechanisms underlying the role of AGR2 in sorafenib resistance and HCC progression remain unknown. We found that sorafenib induces AGR2 secretion via posttranslational modification and that AGR2 plays a critical role in sorafenib-regulated cell viability and endoplasmic reticulum (ER) stress and induces apoptosis in sorafenib-sensitive cells. In sorafenib-sensitive cells, sorafenib downregulates intracellular AGR2 and conversely induces AGR2 secretion, which suppresses its regulation of ER stress and cell survival. In contrast, AGR2 is highly intracellularly expressed in sorafenib-resistant cells, which supports ER homeostasis and cell survival. We suggest that AGR2 regulates ER stress to influence HCC progression and sorafenib resistance. Conclusions This is the first study to report that AGR2 can modulate ER homeostasis via the IRE1α-XBP1 cascade to regulate HCC progression and sorafenib resistance. Elucidation of the predictive value of AGR2 and its molecular and cellular mechanisms in sorafenib resistance could provide additional options for HCC treatment.

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Section: Discussionmentioning

confidence: 99%

Anterior gradient 2 induces resistance to sorafenib via endoplasmic reticulum stress regulation in hepatocellular carcinoma

et al. 2023

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“…This study did not find any attempt to develop an AI-based CDSS specifically for lymphoma. Digital solutions without AI are, however, of potential interest too ( 32 , 70 , 71 ).…”

Section: Discussionmentioning

confidence: 99%

Data-driven support to decision-making in molecular tumour boards for lymphoma: A design science approach

et al. 2022

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BackgroundThe increasing amount of molecular data and knowledge about genomic alterations from next-generation sequencing processes together allow for a greater understanding of individual patients, thereby advancing precision medicine. Molecular tumour boards feature multidisciplinary teams of clinical experts who meet to discuss complex individual cancer cases. Preparing the meetings is a manual and time-consuming process.PurposeTo design a clinical decision support system to improve the multimodal data interpretation in molecular tumour board meetings for lymphoma patients at Karolinska University Hospital, Stockholm, Sweden. We investigated user needs and system requirements, explored the employment of artificial intelligence, and evaluated the proposed design with primary stakeholders.MethodsDesign science methodology was used to form and evaluate the proposed artefact. Requirements elicitation was done through a scoping review followed by five semi-structured interviews. We used UML Use Case diagrams to model user interaction and UML Activity diagrams to inform the proposed flow of control in the system. Additionally, we modelled the current and future workflow for MTB meetings and its proposed machine learning pipeline. Interactive sessions with end-users validated the initial requirements based on a fictive patient scenario which helped further refine the system.ResultsThe analysis showed that an interactive secure Web-based information system supporting the preparation of the meeting, multidisciplinary discussions, and clinical decision-making could address the identified requirements. Integrating artificial intelligence via continual learning and multimodal data fusion were identified as crucial elements that could provide accurate diagnosis and treatment recommendations.ImpactOur work is of methodological importance in that using artificial intelligence for molecular tumour boards is novel. We provide a consolidated proof-of-concept system that could support the end-to-end clinical decision-making process and positively and immediately impact patients.ConclusionAugmenting a digital decision support system for molecular tumour boards with retrospective patient material is promising. This generates realistic and constructive material for human learning, and also digital data for continual learning by data-driven artificial intelligence approaches. The latter makes the future system adaptable to human bias, improving adequacy and decision quality over time and over tasks, while building and maintaining a digital log.

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“…Finally, we obtained the expression data of 37 cancer species after removing those with fewer than three samples in a single cancer species. Through cBioPortal resources, 6 we had analyzed the genetic changes of DDX58 in the TCGA dataset ( Reimer et al, 2021 ). The gene changes and mutation sites of DDX58 were obtained in the “Oncoprint,” “Cancer Type Summary,” and “Mutations” sub modules.…”

Section: Methodsmentioning

confidence: 99%

Systematic analysis of virus nucleic acid sensor DDX58 in malignant tumor

Huang

Jin

et al. 2022

Front. Microbiol.

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IntroductionIn December 2019, a novel epidemic of coronavirus pneumonia (COVID-19) was reported，and population-based studies had shown that cancer was a risk factor for death from COVID-19 infection. However, the molecular mechanism between COVID-19 and cancer remains indistinct. In this paper, we analyzed the nucleic acid sensor (DDX58) of SARS-CoV-2 virus, which is a significant gene related to virus infection. For purpose of clarifying the characteristics of DDX58 expression in malignant tumors, this study began to systematically analyze the DDX58 expression profile in the entire cancer type spectrum.MethodsUsing TCGA pan-cancer database and related data resources, we analyzed the expression, survival analysis, methylation expression, mutation status, microsatellite instability (MSI), immune related microenvironment, gene related network, function and drug sensitivity of DDX58.ResultsThe expression level of DDX58 mRNA in most cancers was higher than the expression level in normal tissues. Through TIMER algorithm mining, we found that DDX58 expression was closely related to various levels of immune infiltration in pan-cancer. The promoter methylation level of DDX58 was significantly increased in multiple cancers. In addition, abnormal expression of DDX58 was related to MSI and TMB in multiple cancers, and the most common type of genomic mutation was “mutation.” In the protein–protein interaction (PPI) network, we found that type I interferon, phagocytosis, ubiquitinase, and tumor pathways were significantly enriched. Finally, according to the expression of DDX58 indicated potential sensitive drugs such as Cediranib, VE−821, Itraconazole, JNJ−42756493, IWR−1, and Linsitinib.DiscussionIn conclusion, we had gained new insights into how DDX58 might contribute to tumor development, and DDX58 could be used as an immune-related biomarker and as a potential immunotherapeutic target for COVID-19 infected cancer patients.

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Challenges and Experiences Extending the cBioPortal for Cancer Genomics to a Molecular Tumor Board Platform

Cited by 12 publications

References 8 publications

Anterior gradient 2 induces resistance to sorafenib via endoplasmic reticulum stress regulation in hepatocellular carcinoma

Anterior gradient 2 induces resistance to sorafenib via endoplasmic reticulum stress regulation in hepatocellular carcinoma

Data-driven support to decision-making in molecular tumour boards for lymphoma: A design science approach

Systematic analysis of virus nucleic acid sensor DDX58 in malignant tumor

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