Inhibition of non-receptor tyrosine kinase LCK partially mitigates mixed granulocytic airway inflammation in a murine model of asthma

Alqarni, Saleh A.; Ahmad, Sheikh F.; Alqahtani, Faleh; Al-Harbi, Naif O.; Alshehri, Samiyah; Ibrahim, Khalid E.; Alfardan, Ali S.; Attia, Sabry M.; Nadeem, Ahmed

doi:10.1016/j.intimp.2023.110225

Cited by 1 publication

(1 citation statement)

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“…High expression of LCK in OC can better predict progression-free survival and OS than a cytolytic activity score 13 . Several clinical trials targeting LCK are currently underway due to its prominent role in the regulation of immunity, involving cancers 8 , 14 , inflammatory diseases 15 , etc. LCK is a downstream molecule in T-cell receptor signaling pathways in several cancer types.…”

Section: Introductionmentioning

confidence: 99%

A multimodal radiomic machine learning approach to predict the LCK expression and clinical prognosis in high-grade serous ovarian cancer

Zhan,

He,

et al. 2023

Sci Rep

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We developed and validated a multimodal radiomic machine learning approach to noninvasively predict the expression of lymphocyte cell-specific protein-tyrosine kinase (LCK) expression and clinical prognosis of patients with high-grade serous ovarian cancer (HGSOC). We analyzed gene enrichment using 343 HGSOC cases extracted from The Cancer Genome Atlas. The corresponding biomedical computed tomography images accessed from The Cancer Imaging Archive were used to construct the radiomic signature (Radscore). A radiomic nomogram was built by combining the Radscore and clinical and genetic information based on multimodal analysis. We compared the model performances and clinical practicability via area under the curve (AUC), Kaplan–Meier survival, and decision curve analyses. LCK mRNA expression was associated with the prognosis of HGSOC patients, serving as a significant prognostic marker of the immune response and immune cells infiltration. Six radiomic characteristics were chosen to predict the expression of LCK and overall survival (OS) in HGSOC patients. The logistic regression (LR) radiomic model exhibited slightly better predictive abilities than the support vector machine model, as assessed by comparing combined results. The performance of the LR radiomic model for predicting the level of LCK expression with five-fold cross-validation achieved AUCs of 0.879 and 0.834, respectively, in the training and validation sets. Decision curve analysis at 60 months demonstrated the high clinical utility of our model within thresholds of 0.25 and 0.7. The radiomic nomograms were robust and displayed effective calibration. Abnormally high expression of LCK in HGSOC patients is significantly correlated with the tumor immune microenvironment and can be used as an essential indicator for predicting the prognosis of HGSOC. The multimodal radiomic machine learning approach can capture the heterogeneity of HGSOC, noninvasively predict the expression of LCK, and replace LCK for predictive analysis, providing a new idea for predicting the clinical prognosis of HGSOC and formulating a personalized treatment plan.

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