Pulmonary Inflammation and KRAS Mutation in Lung Cancer

Keohavong, Phouthone; Di, Y. Peter

doi:10.1007/978-3-030-63046-1_5

Cited by 6 publications

(5 citation statements)

References 150 publications

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“…Kirsten rat sarcoma virus oncogene (KRAS) is the most frequently mutated member of the Ras family in human tumors, usually associated with pancreatic cancer and lung cancer, 43 and one of the most important regulators of cell proliferation, differentiation and survival. 44 COPD is an independent risk factor for lung cancer. KRAS can also affect COPD and iron death through several pathways, but its specific mechanism is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Screening of potential key ferroptosis-related genes in Chronic Obstructive Pulmonary Disease

Cao,

Pan,

Yang

et al. 2023

COPD

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Purpose Ferroptosis plays essential roles in the development of COPD. We aim to identify the potential ferroptosis-related genes of COPD through bioinformatics analysis. Methods The RNA expression profile dataset GSE148004 was obtained from the GEO database. The ferroptosis-related genes were obtained from the FerrDb database. The potential differentially expressed ferroptosis-related genes of COPD were screened by R software. Then, protein–protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for the differentially expressed ferroptosis-related genes. Finally, hub gene-microRNA(miRNA), hug gene-transcription factor interaction networks were constructed by miRTarBase v8.0 and JASPAR respectively, and hub gene drugs were predicted by the Enrichr database. Results A total of 41 differentially expressed ferroptosis-related genes (22 up-regulated genes and 19 down-regulated genes) were identified between 7 COPD patients and 9 healthy controls. The PPI results demonstrated that these ferroptosis-related genes interacted with each other. The GO and KEGG enrichment analyses of differentially expressed ferroptosis-related genes indicated several enriched terms related to ferroptosis, central carbon metabolism in cancer, and the HIF-1 signaling pathway. The crucial miRNAs and drugs associated with the top genes were identified. Conclusion We identified 41 potential ferroptosis-related genes in COPD through bioinformatics analysis. HIF1A, PPARG, and KRAS may affect the development of COPD by regulating ferroptosis. These results may expand our understanding of COPD and might be useful in the treatment of COPD.

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Section: Discussionmentioning

confidence: 99%

Screening of potential key ferroptosis-related genes in Chronic Obstructive Pulmonary Disease

Cao,

Pan,

Yang

et al. 2023

COPD

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“…Rodents animal studies have revealed that chronic inflammation significantly enhances lung carcinogenesis, and inhibition of inflammation suppresses cancer progression and reduces the tumor volume [ 33 ]. Besides, the role of inflammation in increasing the risk of lung tumorigenesis driven primarily by oncogenic KRAS has been researched and the results showed that inflammatory responses may increase KRAS mutation rate and create a vicious cycle of chronic inflammation and KRAS mutation [ 34 ]. Fortunately, many studies have clarified the molecular mechanism and roles of chronic inflammation in lung cancer [ 35 ] and various immune cells, cytokines and signaling pathways participate in inflammation mediated lung carcinogenesis [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

A novel quantitative prognostic model for initially diagnosed non-small cell lung cancer with brain metastases

Liu

et al. 2022

Cancer Cell Int

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Background The prognosis of non-small cell lung cancer (NSCLC) with brain metastases (BMs) had been researched in some researches, but the combination of clinical characteristics and serum inflammatory indexes as a noninvasive and more accurate model has not been described. Methods We retrospectively screened patients with BMs at the initial diagnosis of NSCLC at Sun Yat-Sen University Cancer Center. LASSO-Cox regression analysis was used to establish a novel prognostic model for predicting OS based on blood biomarkers. The predictive accuracy and discriminative ability of the prognostic model was compared to Adjusted prognostic Analysis (APA), Recursive Partition Analysis (RPA), and Graded Prognostic Assessment (GPA) using concordance index (C-index), time-dependent receiver operating characteristic (td-ROC) curve, Decision Curve Analysis(DCA), net reclassification improvement index (NRI), and integrated discrimination improvement index (IDI). Results 10-parameter signature's predictive model for the NSCLC patients with BMs was established according to the results of LASSO-Cox regression analysis. The C-index of the prognostic model to predict OS was 0.672 (95% CI = 0.609 ~ 0.736) which was significantly higher than APA,RPA and GPA. The td-ROC curve and DCA of the predictive model also demonstrated good predictive accuracy of OS compared to APA, RPA and GPA. Moreover, NRI and IDI analysis indicated that the prognostic model had improved prediction ability compared with APA, RPA and GPA. Conclusion The novel prognostic model demonstrated favorable performance than APA, RPA, and GPA for predicting OS in NSCLC patients with BMs.

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“…STK11 is a tumor suppressor encoding for the serine/threonine kinase STK11, also known as liver kinase B1 (LKB1), and it regulates cell polarity and energy metabolism [ 60 ]. In addition, it has been proposed that KRAS mutations might be more common in smoking females than in smoking males [ 61 ], a finding not confirmed by subsequent studies [ 62 ]. Smoking-associated KRAS mutations are mainly transversion mutations (G > T and G > C) and are more frequent in females than in males [ 61 , 63 , 64 ]: In fact, the two most common KRAS mutations in NSCLC are the c.34G > T (p.G12C) and the c.35G > T (p.G12V) changes [ 65 , 66 ], which are more common in females and in current or past smokers [ 62 ].…”

Section: Risk Factors and Kras Mutations In Lung A...mentioning

confidence: 99%

“…In addition, it has been proposed that KRAS mutations might be more common in smoking females than in smoking males [ 61 ], a finding not confirmed by subsequent studies [ 62 ]. Smoking-associated KRAS mutations are mainly transversion mutations (G > T and G > C) and are more frequent in females than in males [ 61 , 63 , 64 ]: In fact, the two most common KRAS mutations in NSCLC are the c.34G > T (p.G12C) and the c.35G > T (p.G12V) changes [ 65 , 66 ], which are more common in females and in current or past smokers [ 62 ]. In contrast, KRAS transition mutations (G > A) are more common in non-smoker patients, suggesting different mechanisms of carcinogenesis [ 63 , 64 ].…”

Section: Risk Factors and Kras Mutations In Lung A...mentioning

confidence: 99%

Molecular Biology and Therapeutic Perspectives for K-Ras Mutant Non-Small Cell Lung Cancers

Cekani

Epistolio

Dazio

et al. 2022

Cancers

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In non-small cell lung cancer (NSCLC) the most common alterations are identified in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, accounting for approximately 30% of cases in Caucasian patients. The majority of mutations are located in exon 2, with the c.34G > T (p.G12C) change being the most prevalent. The clinical relevance of KRAS mutations in NSCLC was not recognized until a few years ago. What is now emerging is a dual key role played by KRAS mutations in the management of NSCLC patients. First, recent data report that KRAS-mutant lung AC patients generally have poorer overall survival (OS). Second, a KRAS inhibitor specifically targeting the c.34G > T (p.G12C) variant, Sotorasib, has been approved by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency. Another KRAS inhibitor targeting c.34G > T (p.G12C), Adagrasib, is currently being reviewed by the FDA for accelerated approval. From the description of the biology of KRAS-mutant NSCLC, the present review will focus on the clinical aspects of KRAS mutations in NSCLC, in particular on the emerging efficacy data of Sotorasib and other KRAS inhibitors, including mechanisms of resistance. Finally, the interaction between KRAS mutations and immune checkpoint inhibitors will be discussed.

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Pulmonary Inflammation and KRAS Mutation in Lung Cancer

Cited by 6 publications

References 150 publications

Screening of potential key ferroptosis-related genes in Chronic Obstructive Pulmonary Disease

Screening of potential key ferroptosis-related genes in Chronic Obstructive Pulmonary Disease

A novel quantitative prognostic model for initially diagnosed non-small cell lung cancer with brain metastases

Molecular Biology and Therapeutic Perspectives for K-Ras Mutant Non-Small Cell Lung Cancers

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