Role of novel cancer gene SLITRK3 to activate NTRK3 in squamous cell lung cancer

Bollig‐Fischer, Aliccia; Bao, Bin; Manning, Morenci; Dyson, Greg; Michelhaugh, Sharon K.; Mittal, Sandeep; Bepler, Gerold; Mamdani, Hirva

doi:10.1186/s43556-021-00051-2

Cited by 8 publications

(5 citation statements)

References 47 publications

(67 reference statements)

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“…SLITRK3 combined with NIH staging has strong predictive and prognostic value and is a feasible biomarker for clinical use in GIST (24). Meanwhile, high SLITRK3 expression is associated with a poor outcome in LUSC, and it can activate NTRK3 to promote suppressed cancer stem cell phenotypes (25). However, despite the basic and clinical research conducted on some genes, the role of other genes and their value in future targeted therapies have not yet been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and Therapeutic Response Analysis of Breast Cancer Based on Post-translational Ubiquitin and Ubiquitin-Like Modification-Related Signature

Zhou

Kong

Lin

et al. 2023

Preprint

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Background: Ubiquitin and ubiquitin-like (UUL) modifications play pleiotropic functions and are subject to fine regulatory mechanisms frequently altered in cancer. However, the comprehensive impact of UUL modification on breast cancer remains unclear. Methods: Transcriptomic and clinical data of breast cancer were downloaded from TCGA and GEO databases. Molecular subtyping of breast cancer was conducted using the NMF and CIBERSORT algorithms. Prognostic genes were identified via univariate, lasso and multivariate Cox regression analyses. Clinical pathological features, immune cell infiltration, immune therapeutic response and chemotherapy drug sensitivity were compared between groups using the Wilcoxon test. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Results: In breast cancer, 63 UUL modification-related genes were differentially expressed, with 29 up-regulated and 34 down-regulated genes. These genes were used to generate two UUL modification patterns that exhibited significant differences in prognostic features and immune cell infiltration. The UUL modification patterns were associated with 2038 differentially expressed genes that were significantly enriched in nuclear division, chromosome segregation, neuroactive ligand-receptor interaction, cell cycle, and other biological processes. Of these genes, 425 were associated with breast cancer prognosis, which enabled the classification of breast cancer into two clusters with significantly distinct prognoses. We developed a prognostic model, UULscore, which comprised nine genes and showed a significant correlation with partial immune cell infiltration. Furthermore, UULscore demonstrated potential predictive value in breast cancer overall survival prediction, immune therapeutic response, and chemotherapy drug sensitivity. UULscore, stage, radiotherapy, and chemotherapy were identified as independent prognostic factors for breast cancer. Based on these factors, a nomogram model was constructed, which demonstrated exceptional prognostic predictive performance. Conclusion: In conclusion, we identified two UUL modification-derived molecular subtypes in breast cancer, and have successfully constructed a risk scoring model that holds potential value in prognosis, immune infiltration, immune therapeutic response, and chemotherapy drug sensitivity.

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Section: Discussionmentioning

confidence: 99%

Prognostic and Therapeutic Response Analysis of Breast Cancer Based on Post-translational Ubiquitin and Ubiquitin-Like Modification-Related Signature

Zhou

Kong

Lin

et al. 2023

Preprint

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“…[ 21 ] Moreover, increased expression of SLITRK3 in LUSC has been linked to unfavorable clinical outcomes, potentially attributable to its function in facilitating SLITRK3-mediated activation of NTRK3, thereby promoting a cancer stem cell phenotype. [ 22 ] Despite the identification and study of some genes, those involved in BC remain largely unexplored. Therefore, further research is crucial.…”

Section: Discussionmentioning

confidence: 99%

A prognostic signature associated with cell senescence predicts survival outcomes and strongly associates with immunotherapy and chemotherapy response in breast cancer

Pan

et al. 2023

Medicine

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The objective of this study is to assess the predictive potency of cell senescence-related genes (CSRGs) in breast cancer (BC) and establish a risk signature. Trascriptome data of CSRGs were obtained from the TCGA and GEO databases. Consensus clustering was used to generate CSRGs-based molecular clusters for BC patients. A CSRGs-derived risk signature was built using multiple Cox regression analyses of differentially expressed genes (DEGs) between clusters. The prognosis, immune infiltration, chemotherapy and immunotherapy response between different risk groups were analyzed and compared. Two molecular clusters of BC patients were generated on the basis of 79 differentially expressed CSRGs, which showed distinct prognosis and immune infiltration. A total of 1403 DEGs between the CSRGs-derived clusters were found, and 10 of them were independent prognostic genes that used to construct a risk signature. The results demonstrated that patients with older age and advanced stage presented with a higher risk scores. In addition, the risk signature was found to be associated with outcomes, immune infiltration, chemotherapy and immunotherapy response. Patients in the low-risk group showed a favorable prognosis and higher immunotherapy response than those in the high-risk group. Finally, we developed a highly stable nomogram that incorporates risk signature, chemotherapy, radiotherapy, and stage variables, enabling accurate prediction of the overall survival (OS) of individual patients. To conclude, the signature derived from CSRGs holds great promise as a biomarker for prognostic assessment of BC and may serve as a valuable tool in guiding immunotherapy.Abbreviations: BC = breast cancer, CCL19 = C-C motif chemokine ligand 19, CSRGs = cell senescence-related genes, DCs = dendritic cells, DEGs = differentially expressed genes, GO = gene ontology, IPS = immunophenoscore, KEGG = Kyoto encyclopedia of genes and genomes, NET = neutrophil extracellular trap, OS = overall survival, SHCBP1 = SHC binding and spindle-associated 1, TIDE = tumor immune dysfunction and exclusion.

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“…SLITRK5 mediates BDNF-dependent NTRK2 (TrkB) trafficking and signaling [56]. SLITRK3 activates NTRK3 in squamous cell lung cancer [8]. On the other hand, MPRIP stands at the top with P δ = 13.1%.…”

Section: Ntrk Clustermentioning

confidence: 99%

Gene Cluster Expression Index (GCEI) and Potential Indications for Targeted Therapy and Immunotherapy

Rao¹

2023

Preprint

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Lung cancer recurrence risk was demonstrated to be related to driver gene and immunotherapy target gene cluster expression abnormality. Nine clusters seeded with driver genes ALK, BRAF, EGFR, MET, NTRK, RAS, RET, ROS1, TP53 and two immunotherapy target genes PDCD1 and CTLA4 were investigated respectively to predict lung cancer recurrence. The cluster of a seed was pre-selected to include fusion partner genes in the case of gene fusion, ligands, its pseudogenes, upstream and downstream co-expressors or inhibiting genes, effectors directly related to important pathways, etc. For each cluster, a gene cluster expression index (GCEI) was defined in two steps: Firstly, apply univariate ROC based on a member's expression vector to predict recurrences so as to label a patient sample as either normal or abnormal with respect to the member gene; Secondly, apply ROC based on the percentage of abnormal member genes in a cluster so as to predict recurrences and an optimal threshold is derived so that a sample is labeled as abnormal with respect to the cluster expression profile if the the percentage of abnormal genes for the sample is greater than or equal to the threshold, or else it is labeled as normal. Combinatory GCEI was developed as a binary string concatenating the individual GCEI corresponding to the individual cluster in an ordered list of driver or other important gene seeds. It showed that the recurrence risk of the abnormal group with respect to a given cluster is typically 150% to 200% of the normal counterpart. Finally it was proposed and discussed to expand targeted therapy and immunotherapy to the abnormal group defined by GCEI status.

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Role of novel cancer gene SLITRK3 to activate NTRK3 in squamous cell lung cancer

Cited by 8 publications

References 47 publications

Prognostic and Therapeutic Response Analysis of Breast Cancer Based on Post-translational Ubiquitin and Ubiquitin-Like Modification-Related Signature

Prognostic and Therapeutic Response Analysis of Breast Cancer Based on Post-translational Ubiquitin and Ubiquitin-Like Modification-Related Signature

A prognostic signature associated with cell senescence predicts survival outcomes and strongly associates with immunotherapy and chemotherapy response in breast cancer

Gene Cluster Expression Index (GCEI) and Potential Indications for Targeted Therapy and Immunotherapy

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