Prognostic value of TP53 co-mutation status combined with EGFR mutation in patients with lung adenocarcinoma

Wang, Feng; Zhao, Ning; Gao, Ge; Deng, Hong-Bin; Wang, Zhihui; Deng, Lili; Yu, Yang; Lu, Changlian

doi:10.1007/s00432-020-03340-5

Cited by 32 publications

(24 citation statements)

References 24 publications

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“…old, which was consistent with the results of previous studies [ 32 , 33 ]. We also confirmed that TP53 mutation did not affect the prognosis of patients with LUAD, it was consistent with the result of the study by Szymanowska, A., et al [ 34 – 39 ].…”

Section: Discussionsupporting

confidence: 93%

“…We also confirmed that TP53 mutation did not affect the prognosis of patients with LUAD, it was consistent with the result of the study by Szymanowska, A., et al [ 34 – 39 ]. However, other studies suggested that patients with mutation of the TP53 gene had a poor prognosis [ 15 , 32 , 33 , 40 , 41 ]. This phenomenon was worth studying.…”

Section: Discussionmentioning

confidence: 99%

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Differences in genetics and microenvironment of lung adenocarcinoma patients with or without TP53 mutation

Zeng

et al. 2021

BMC Pulm Med

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Background Differences in genetics and microenvironment of LUAD patients with or without TP53 mutation were analyzed to illustrate the role of TP53 mutation within the carcinogenesis of LUAD, which will provide new concepts for the treatment of LUAD. Methods In this study, we used genetics and clinical info from the TCGA database, including somatic mutations data, RNA-seq, miRNA-seq, and clinical data. More than one bioinformatics tools were used to analyze the unique genomic pattern of TP53-related LUAD. Results According to TP53 gene mutation status, we divided the LUAD patients into two groups, including 265 in the mutant group (MU) and 295 in the wild-type group (WT). 787 significant somatic mutations were detected between the groups, including mutations in titin (TTN), type 2 ryanodine receptor (RYR2) and CUB and Sushi multiple domains 3(CSMD3), which were up-regulated in the MU. However, no significant survival difference was observed. At the RNA level, we obtained 923 significantly differentially expressed genes; in the MU, α-defensin 5(DEFA5), pregnancy-specific glycoprotein 5(PSG5) and neuropeptide Y(NPY) were the most up-regulated genes, glucose-6-phosphatase (G6PC), alpha-fetoprotein (AFP) and carry gametocidal (GC) were the most down-regulated genes. GSVA analysis revealed 30 significant pathways. Compared with the WT, the expression of 12 pathways in the mutant group was up-regulated, most of which pointed to cell division. There were significant differences in tumor immune infiltrating cells, such as Macrophages M1, T cells CD4 memory activated, Mast cells resting, and Dendritic cells resting. In terms of immune genes, a total of 35 immune-related genes were screened, of which VGF (VGF nerve growth factor inducible) and PGC (peroxisome proliferator-activated receptor gamma coactivator) were the most significant up-regulated and down-regulated genes, respectively. Research on the expression pattern of immunomodulators found that 9 immune checkpoint molecules and 6 immune costimulatory molecules were considerably wholly different between the two groups. Conclusions Taking the mutant group as a reference, LUAD patients in the mutant group had significant differences in somatic mutations, mRNA-seq, miRNA-seq, immune infiltration, and immunomodulators, indicating that TP53 mutation plays a crucial role in the occurrence and development of LUAD.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Differences in genetics and microenvironment of lung adenocarcinoma patients with or without TP53 mutation

Zeng

et al. 2021

BMC Pulm Med

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“…We also studied the associations of mutations with clinical features and outcomes. We found that the TP53 gene had a higher mutation rate in people younger than or equal to 65 years old, reaching 53.8%, and it was only 40% in people over 65 years old, which was consistent with the results of previous studies [32,33]. We also con rmed that TP53 mutations did not affect the prognosis of patients with LUAD, it was consistent with the result of the study by Szymanowska, A., et al [34][35][36][37][38][39].…”

Section: Discussionsupporting

confidence: 92%

“…We also con rmed that TP53 mutations did not affect the prognosis of patients with LUAD, it was consistent with the result of the study by Szymanowska, A., et al [34][35][36][37][38][39]. However, other studied suggested that patients with mutations of the TP53 gene had a poor prognosis [15,32,33,40,41]. This phenomenon was worth studying.…”

Section: Discussionsupporting

confidence: 91%

Differences in Genetics and Microenvironment of Lung Adenocarcinoma Patients with or without TP53 Mutation

Zeng

et al. 2021

Preprint

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Background: Differences in genetics and microenvironment of lung adenocarcinoma (LUAD) patients with or without TP53 mutation were analyzed to illustrate the role of TP53 mutation within the carcinogenesis of LUAD, which will provide new concepts for the treatment of LUAD.Methods: In this study, we used genetics and clinical info from the TCGA database, including somatic mutations data, RNA-seq, miRNA-seq, and clinical data. More than one bioinformatics tools were used to analyze the unique genomic pattern of TP53-related LUAD.Results: According to TP53 gene mutation status, we divided the LUAD patients into two groups, including 265 in the mutant group (MU) and 295 in the wild-type group (WT). 787 significant somatic mutations were detected between the groups, includingmutations in titin (TTN), type 2 ryanodine receptor (RYR2) and CUB and Sushi multiple domains 3(CSMD3), which were up-regulated in the MU. However, no significant survival difference was observed. At the RNA level, we obtained 923 significantly differentially expressed genes; in the MU, α-defensin 5(DEFA5),pregnancy-specific glycoprotein 5(PSG5) and neuropeptide Y(NPY) were the most up-regulated genes, glucose-6-phosphatase (G6PC), alpha-fetoprotein (AFP) and carry gametocidal (GC) were the most down-regulated genes. GSVA analysis revealed 30 significant pathways. Compared with the WT, the expression of 12 pathways in the mutant group was up-regulated, most of which pointed to cell division. There were significant differences in tumor immune infiltrating cells, such as Macrophages M1, T cells CD4 memory activated, Mast cells resting, and Dendritic cells resting. In terms of immune genes, a total of 35 immune-related genes were screened, of which VGF (VGF nerve growth factor inducible) and PGC (peroxisome proliferator-activated receptor gamma coactivator) were the most significant up-regulated and down-regulated genes, respectively. Research on the expression pattern of immunomodulators found that 9 immune checkpoint molecules and 6 immune costimulatory molecules were considerably wholly different between the two groups.Conclusion: Taking the mutant group as a reference, LUAD patients in the mutant group had significant differences in somatic mutations, mRNA-seq, miRNA-seq, immune infiltration, and immunomodulators, indicating that TP53 mutation plays a crucial role in the occurrence and development of LUAD.

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“…Catherine Labbé et al demonstrated that patients with dual TP53/EGFR mutations, especially missense mutations, had marginally lower response rates and shorter PFS when treated with EGFR TKI therapy [23]. Feng Wang et al also showed that mutant TP53 is a poor prognostic factor in LUAD patients, and the prognosis of TP53/EGFR co-mutation is worse [24]. They also demonstrated that, there was no signi cant difference in OS bene t when patients with EGFR mutations were compared with those with EGFR wild type.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of NDRG2 combined with EGFR-sensitizing mutations in lung adenocarcinoma 

Yang¹,

Ji²,

Feng³

et al. 2020

Preprint

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Background: N-myc downstream-regulated gene 2 (NDRG2) plays a substantial role in lung adenocarcinoma (LUAD). Epidermal growth factor receptor (EGFR)-sensitizing mutation could significantly improve prognosis in patients with LUAD. Here, we aimed to elucidate the prognostic value of NDRG2 combined with EGFR-sensitizing mutations in patients with LUAD. Methods: Lung parenchyma specimens obtained during surgery or CT-guide percutaneous lung puncture biopsy for the NDRG2 protein and EGFR genomic testing were obtained. Associations between NDRG2/EGFR and clinicopathological characteristics of patients with LUAD were extracted from the Tianjin First Central Hospital in China between June 2013 and June 2014. Results: The expression of NDRG2 was significantly decreased in patients with LUAD. Expressions of NDRG2 and EGFR-sensitizing mutations showed positive correlations with survival. ROC curve analyses showed that the diagnostic value of NDRG2 combined with EGFR in LUAD was significantly higher than that of each biomarker alone. Expression of NDRG2 and EGFR-sensitizing mutations were associated with the longer overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). Advanced stages were significantly associated with low expression of NDRG2. In multivariate analysis, compared with other patients, NDRG2 (+)/EGFR (+) was independently associated with prolonged OS and PFS. Conclusion: NDRG2 combined with EGFR-sensitizing mutations might be valuable markers to evaluate the prognosis of LUAD patients.

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Prognostic value of TP53 co-mutation status combined with EGFR mutation in patients with lung adenocarcinoma

Cited by 32 publications

References 24 publications

Differences in genetics and microenvironment of lung adenocarcinoma patients with or without TP53 mutation

Differences in genetics and microenvironment of lung adenocarcinoma patients with or without TP53 mutation

Differences in Genetics and Microenvironment of Lung Adenocarcinoma Patients with or without TP53 Mutation

Prognostic significance of NDRG2 combined with EGFR-sensitizing mutations in lung adenocarcinoma

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Prognostic value of TP53 co-mutation status combined with EGFR mutation in patients with lung adenocarcinoma

Cited by 32 publications

References 24 publications

Differences in genetics and microenvironment of lung adenocarcinoma patients with or without TP53 mutation

Differences in genetics and microenvironment of lung adenocarcinoma patients with or without TP53 mutation

Differences in Genetics and Microenvironment of Lung Adenocarcinoma Patients with or without TP53 Mutation

Prognostic significance of NDRG2 combined with EGFR-sensitizing mutations in lung adenocarcinoma&nbsp;

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Prognostic significance of NDRG2 combined with EGFR-sensitizing mutations in lung adenocarcinoma