ERK phosphorylation as a marker of RAS activity and its prognostic value in non-small cell lung cancer

Reissig, Timm M.; Sara, Linda; Ting, Saskia; Reis, Henning; Metzenmacher, Martin; Eberhardt, Wilfried; Zaun, Gregor; Herold, Thomas; Aigner, Clemens; Darwiche, Kaid; Stuschke, Martin; Schildhaus, Hans–Ulrich; Schüler, Martin; Wiesweg, Marcel

doi:10.1016/j.lungcan.2020.09.005

Cited by 10 publications

(5 citation statements)

References 32 publications

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“…At the same time, KRAS is present in 35% of lung adenocarcinomas (LUADs) 33 . Research has proven ERK phosphorylation as a marker of RAS activity and its prognostic value in non‐small cell lung cancer 34 . Hyperactivation of ERK by multiple mechanisms is toxic to RTK‐RAS mutation‐driven lung adenocarcinoma cells 35 .…”

Section: Discussionmentioning

confidence: 99%

“… 33 Research has proven ERK phosphorylation as a marker of RAS activity and its prognostic value in non‐small cell lung cancer. 34 Hyperactivation of ERK by multiple mechanisms is toxic to RTK‐RAS mutation‐driven lung adenocarcinoma cells. 35 This may provide us with a new direction for studying the relationship between DARS2 and KRAS mutations in lung adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

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DARS2 promotes the occurrence of lung adenocarcinoma via the ERK/c‐Myc signaling pathway

Fang,

Jiang,

et al. 2023

Thoracic Cancer

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BackgroundDARS2 expression is upregulated in lung adenocarcinoma (LUAD) which correlates with tumor patient stage and prognosis. The mechanism of DARS2 involvement in LUAD still needs to be further explored.MethodsIn this study, we found that DARS2 expression in LUAD tissue was significantly higher than that in normal tissue. At the same time, the Kaplan–Meier curve showed that the survival prognosis of LUAD patients with high expression of DARS2 was significantly worse than low expression of DARS2. The expression of DARS2 was detected in LUAD and adjacent normal tissues by IHC staining, histochemical scoring and a survival curve was generated. In addition, we demonstrated that the knockdown and overexpression of DARS2 significantly affected the proliferation, invasion, and migration of LUAD cells in vitro and in vivo. Finally, western blot and rescue assay were performed on LUAD cells to further explore and verify the signaling pathway.ResultsDARS2 expression was significantly upregulated in LUAD tissues and cell lines. What is more, the increased expression of DARS2 was closely related to proliferation, invasion and metastasis. The tumorigenic assay in nude mice further showed that the tumorigenic ability of nude mice was significantly improved with the increase in DARS2 expression. Finally, we determined that DARS2 plays its role in LUAD by targeting the ERK/c‐Myc signaling pathway.ConclusionOur data revealed the oncogenic role of DARS2 in LUAD, indicating that DARS2 may be a predictive biomarker and novel therapeutic target for LUAD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

DARS2 promotes the occurrence of lung adenocarcinoma via the ERK/c‐Myc signaling pathway

Fang,

Jiang,

et al. 2023

Thoracic Cancer

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“…Of these, Ras, MAPK, and PI3K-Akt signaling pathways have been elucidated in different lung diseases. For example, ERK phosphorylation as a marker of Ras activity has shown prognostic value in non-small cell lung cancer ( 40 ), and exposure to mold proteases stimulated mucin production in airway epithelial cells through Ras/Raf1/ERK signal pathway ( 41 ). Furthermore, Apelin-36 protects against lipopolysaccharide-induced acute lung injury by inhibiting the ASK1/MAPK signaling pathway ( 42 ), whereas fibro growth factor-2 protects against acute lung injury by activating the PI3K/Akt signaling pathway ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

Analysis of miRNA Profiles and the Regulatory Network in Congenital Pulmonary Airway Malformations

et al. 2021

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Background: Specific diagnostic markers for congenital pulmonary airway malformations (CPAMs) have not yet been discovered. This study intends to detect differentially expressed miRNAs in type I and type II CPAMs by using a miRNA chip and clarify the feasibility of miRNAs as different CPAM typing markers.Methods: Lung tissues of type I and type II CPAMs were collected and used to assess the differentially expressed miRNAs using a miRNA chip after evaluation using hematoxylin–eosin staining and Masson staining. Quantitative reverse transcription-polymerase chain reaction and fluorescence in situ hybridization were used to verify the quality of the miRNA chip. The function and pathways of related differentially expressed miRNAs were analyzed by Gene Ontology Enrichment (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, respectively. Targets of miRNAs were predicted by targetscan7.1 and mirdbV6 and the network between miRNA and mRNA was established using Cystoscope software.Results: In total, 394/34 upregulated and 321/72 downregulated miRNAs were found in type I and type II CPAMs, respectively. GO and KEGG analysis showed that different pathways are involved in the regulation of CPAM, including platelet activation, Ras, MAPK, FoxO, and PI3K-Akt signaling pathways. miRNA–mRNA network analysis confirmed four major miRNAs in CPAM, including miR-4731-5p to complexin 2, miR-3150a-3p to vesicle amine transport 1, miR-32-5p to F-box and WD repeat domain containing 7, and miR-454-3p to SLAIN motif family member 1.Conclusion: In summary, we have identified four candidate miRNAs and pathways related to different pattern CPAMs, which provide a new perspective for CPAM research and treatment.

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“…Prior to sequencing, specimens were reviewed by an independent pathologist for consistency with the previously established diagnosis. DNA extraction from formalin-fixed, paraffin-embedded (FFPE) tumor tissue, next-generation sequencing (NGS) and bioinformatics were carried out as previously described [ 14 , 15 ].…”

Section: Methodsmentioning

confidence: 99%

Treatment of RET-Positive Advanced Medullary Thyroid Cancer with Multi-Tyrosine Kinase Inhibitors—A Retrospective Multi-Center Registry Analysis

Koehler

Adam

Fuß

et al. 2022

Cancers

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Background: RET (rearranged during transfection) variants are the most prevalent oncogenic events in medullary thyroid cancer (MTC). In advanced disease, multi-tyrosine kinase inhibitors (MKIs) cabozantinib and vandetanib are the approved standard treatment irrespective of RET status. The actual outcome of patients with RET-positive MTC treated with MKIs is ill described. Methods: We here retrospectively determined the RET oncogene variant status with a targeted DNA Custom Panel in a prospectively collected cohort of 48 patients with advanced MTC treated with vandetanib and/or cabozantinib at four German referral centers. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method. Results: In total, 44/48 (92%) patients had germline or somatic RET variants. The M918T variant was found in 29/44 (66%) cases. In total, 2/32 (6%) patients with a somatic RET variant had further somatic variants, while in 1/32 (3%) patient with a germline RET variant, additional variants were found. Only 1/48 (2%) patient had a pathogenic HRAS variant, and no variants were found in 3 cases. In first-line treatment, the median OS was 53 (95% CI (95% confidence interval), 32–NR (not reached); n = 36), and the median PFS was 21 months (12–39; n = 33) in RET-positive MTC patients. In second-line treatment, the median OS was 18 (13–79; n = 22), and the median PFS was 3.5 months (2–14; n = 22) in RET-positive cases. Conclusions: RET variants were highly prevalent in patients with advanced MTC. The treatment results in RET-positive cases were similar to those reported in unselected cohorts.

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ERK phosphorylation as a marker of RAS activity and its prognostic value in non-small cell lung cancer

Cited by 10 publications

References 32 publications

DARS2 promotes the occurrence of lung adenocarcinoma via the ERK/c‐Myc signaling pathway

DARS2 promotes the occurrence of lung adenocarcinoma via the ERK/c‐Myc signaling pathway

Analysis of miRNA Profiles and the Regulatory Network in Congenital Pulmonary Airway Malformations

Treatment of RET-Positive Advanced Medullary Thyroid Cancer with Multi-Tyrosine Kinase Inhibitors—A Retrospective Multi-Center Registry Analysis

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