Exploring cancer in <i><scp>LRRK</scp>2</i> mutation carriers and idiopathic Parkinson's disease

Warø, Bjørg; Aasly, Jan

doi:10.1002/brb3.858

Cited by 22 publications

(20 citation statements)

References 36 publications

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“…Despite the associations with the specific cancers mentioned previously, we did not observe increased risks of hormone‐related cancers and breast cancer, as reported in our previous study . Two other studies also reported increased risks of breast cancer among LRKK2 ‐PD patients, and these populations were in part included in the pooled analysis. One of the differences is that the numbers of self‐reported cancers were much lower in the international LRRK2 ‐PD consortium.…”

Section: Discussioncontrasting

confidence: 86%

Cancer outcomes among Parkinson's disease patients with leucine rich repeat kinase 2 mutations, idiopathic Parkinson's disease patients, and nonaffected controls

et al. 2019

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Background: Increased cancer risk has been reported in Parkinson’s disease (PD) patients carrying the leucine rich repeat kinase 2 (LRRK2) G2019S mutation (LRRK2-PD) in comparison with idiopathic PD (IPD). It is unclear whether the elevated risk would be maintained when compared with unaffected controls. Methods: Cancer outcomes were compared among 257 LRRK2-PD patients, 712 IPD patients, and 218 controls recruited from 7 LRRK2 consortium centers using mixed-effects logistic regression. Data were then pooled with a previous study to examine cancer risk between 401 LRRK2-PD and 1946 IPD patients. Results: Although cancer prevalence was similar among LRRK2-PD patients (32.3%), IPD patients (27.5%), and controls (27.5%; P = 0.33), LRRK2-PD had increased risks of leukemia (odds ratio [OR] = 4.55; 95% confidence interval [CI], 1.46–10.61) and skin cancer (OR = 1.61; 95% CI, 1.09–2.37). In the pooled analysis, LRRK2-PD patients had also elevated risks of leukemia (OR = 9.84; 95% CI, 2.15–44.94) and colon cancer (OR = 2.34; 95% CI, 1.15–4.74) when compared with IPD patients. Conclusions: The increased risks of leukemia as well as skin and colon cancers among LRRK2-PD patients suggest that LRRK2 mutations heighten risks of certain cancers.

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Section: Discussioncontrasting

confidence: 86%

Cancer outcomes among Parkinson's disease patients with leucine rich repeat kinase 2 mutations, idiopathic Parkinson's disease patients, and nonaffected controls

et al. 2019

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“…LRRK2 mutation carriers have an increased risk of developing nonskin–associated cancers. A significant correlation was found between female mutations and breast cancer (Waro & Aasly, ), and LRRK2 amplification was associated with kidney and thyroid cancer (Looyenga et al, ). It is well‐known that PLAUR plays a significant role in cell proliferation, migration, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of a six‐gene prognostic signature for oral squamous cell carcinoma

Wang

Kong

et al. 2019

Journal Cellular Physiology

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Oral squamous cell carcinoma (OSCC) is one of the most common types of malignancies worldwide, and its morbidity and mortality have increased in the near term. Consequently, the purpose of the present study was to identify the notable differentially expressed genes (DEGs) involved in their pathogenesis to obtain new biomarkers or potential therapeutic targets for OSCC. The gene expression profiles of the microarray datasets GSE85195, GSE23558, and GSE10121 were obtained from the Gene Expression Omnibus (GEO) database. After screening the DEGs in each GEO dataset, 249 DEGs in OSCC tissues were obtained. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathway enrichment analysis was employed to explore the biological functions and pathways of the above DEGs. A protein-protein interaction network was constructed to obtain a central gene. The corresponding total survival information was analyzed in patients with oral cancer from The Cancer Genome Atlas (TCGA). A total of six candidate genes (CXCL10, OAS2, IFIT1, CCL5, LRRK2, and PLAUR) closely related to the survival rate of patients with oral cancer were identified, and expression verification and overall survival analysis of six genes were performed based on TCGA database. Timedependent receiver operating characteristic curve analysis yields predictive accuracy of the patient's overall survival. At the same time, the six genes were further verified by quantitative real-time polymerase chain reaction using samples obtained from the patients recruited to the present study. In conclusion, the present study identified the prognostic signature of six genes in OSCC for the first time via comprehensive bioinformatics analysis, which could become potential prognostic markers for OCSS and may provide potential therapeutic targets for tumors.

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“…Not surprising, the Jak2 knockdown array generated the most similar gene signature as our CypA inhibition array, further confirming the relationship between these enzymes. It is interesting to note that leucine-rich repeat kinase 2 (LRRK2) mutant that induces progressive degeneration of human neural stem cells ( Liu et al., 2012 ) is also associated with breast cancer ( Waro and Aasly, 2018 ), but its mechanistic role is poorly understood. Glycogen synthase kinase 3β (GSKβ) interacts with the PRLr ( Plotnikov et al., 2008 ) and is activated by the PRLr, hence the relation between it and the NIM811 gene set.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the Activity of Cyclophilin A Impedes Prolactin Receptor-Mediated Signaling, Mammary Tumorigenesis, and Metastases

Hakim¹,

Craig²,

Koblinski³

et al. 2020

iScience

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Summary Prolactin (PRL) and its receptor (PRLr) play important roles in the pathogenesis of breast cancer. Cyclophilin A (CypA) is a cis-trans peptidyl-prolyl isomerase (PPI) that is constitutively associated with the PRLr and facilitates the activation of the tyrosine kinase Jak2. Treatment with the non-immunosuppressive prolyl isomerase inhibitor NIM811 or CypA short hairpin RNA inhibited PRL-stimulated signaling, breast cancer cell growth, and migration. Transcriptomic analysis revealed that NIM811 inhibited two-thirds of the top 50 PRL-induced genes and a reduction in gene pathways associated with cancer cell signaling. In vivo treatment of NIM811 in a TNBC xenograft lessened primary tumor growth and induced central tumor necrosis. Deletion of CypA in the MMTV-PyMT mouse model demonstrated inhibition of tumorigenesis with significant reduction in lung and lymph node metastasis. The regulation of PRLr/Jak2-mediated biology by NIM811 demonstrates that a non-immunosuppressive prolyl isomerase inhibitor can function as a potential breast cancer therapeutic.

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Exploring cancer in LRRK2 mutation carriers and idiopathic Parkinson's disease

Cited by 22 publications

References 36 publications

Cancer outcomes among Parkinson's disease patients with leucine rich repeat kinase 2 mutations, idiopathic Parkinson's disease patients, and nonaffected controls

Cancer outcomes among Parkinson's disease patients with leucine rich repeat kinase 2 mutations, idiopathic Parkinson's disease patients, and nonaffected controls

Identification of a six‐gene prognostic signature for oral squamous cell carcinoma

Inhibition of the Activity of Cyclophilin A Impedes Prolactin Receptor-Mediated Signaling, Mammary Tumorigenesis, and Metastases

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