TP53 mutations and SNPs as prognostic and predictive factors in patients with breast cancer (Review)

Huszno, Joanna; Grzybowska, Ewa

doi:10.3892/ol.2018.8627

Cited by 40 publications

(50 citation statements)

References 62 publications

(70 reference statements)

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“…9 However, when mutated, loss of these functions results in abnormal cell proliferation and promotes cancer. 10 TP53 mutations, mainly missense mutations, are also the most common mutations in NSCLC, and are more prevalent in LUSC than in LUAD. [11][12][13] Epidemiological studies have reported that TP53 mutations are closely related to smoking, and it occurring more frequently in patients with tobacco-associated lung cancer than in never-smokers.…”

Section: Introductionmentioning

confidence: 99%

A TP53 -associated gene signature for prediction of prognosis and therapeutic responses in lung squamous cell carcinoma

Lin

et al. 2020

OncoImmunology

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The tumor-suppressor gene tumor protein p53 (TP53) is one of the most commonly mutated genes in human lung cancer, and TP53 mutations are associated with a worsened prognosis and causes resistance to cancer therapy. RNA sequencing and TP53 mutation data were downloaded to determine specific TP53associated signature based on differentially expressed genes between patients with lung squamous cell carcinoma (LUSC) with wild type (TP53 WT) and mutated (TP53 MUT) TP53. We investigated the predictive value of this signature on the immune microenvironment, tumor mutational burden (TMB), and likelihood of response to immunotherapy and chemotherapy. In total, 1,556 differentially expressed genes were identified based on TP53 mutation status. Three genes (KLK6, MUC22 and CSN1S1) identified by univariate and multivariate Cox regression analyses, comprised the prognostic signature which was an independent and specific prognostic marker of overall survival in patients with LUSC. A nomogram was also established to validate this signature for clinical use. Moreover, the high-risk group was characterized by increased infiltration of monocytes and macrophages M1, and decreased T cells CD8 and T cells follicular helper. Highrisk group exhibited a higher TMB, and was much more sensitive to immunotherapy and chemotherapy. KLK6 and CSN1S1 expression and the prognostic prediction values were further validated in clinical samples. The derived TP53-associated signature is a specific and independent prognostic biomarker for LUSC patients, and could provide potential prognostic biomarker or therapeutic targets for the development of novel immunotherapies and chemotherapies.

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Section: Introductionmentioning

confidence: 99%

A TP53 -associated gene signature for prediction of prognosis and therapeutic responses in lung squamous cell carcinoma

Lin

et al. 2020

OncoImmunology

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“…Here we discussed the important roles of those genes and their potential as tangeretin targets against metastatic breast cancer cells. TP53 encodes tumor protein p53, a tumor suppressor gene (15). Mutation in TP53 occurs in human epidermal growth factor receptor 2-positive (15), estrogen receptor-positive, and progesterone-positive breast cancer subtypes (16).…”

Section: Discussionmentioning

confidence: 99%

Integrative Bioinformatics Study Reveals Tangeretin Targets and Molecular Mechanisms Against Metastatic Breast Cancer

Hermawan

Putri

Hanif

et al. 2020

Preprint

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Background: Agents that target metastasis are important to improve treatment efficacy in patients with breast cancer. Tangeretin, a citrus flavonoid, exhibits antimetastatic effects on breast cancer cells, but its molecular mechanism remains unclear.Results: Tangeretin targets were retrieved from PubChem, whereas metastatic breast cancer regulatory genes were downloaded from PubMed. In total, 58 genes were identified as potential therapeutic target genes of tangeretin (PTs). Gene ontology analysis with Webgestalt showed that the PTs participate in the biological process of stimulus response, are the cellular components of the nucleus and the membrane, and play molecular roles in enzyme regulation. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the PTs regulate the PI3K/Akt pathway. Genetic alterations for each target gene were MTOR (3%), NOTCH1 (4%), TP53 (42%), MMP9 (4%), NFKB1 (3%), PIK3CA (32%), PTGS2 (15%), and RELA (5%). The Kaplan–Meier plot displayed that patients with low mRNA expression levels of MTOR, TP53, MMP9, NFKB1, PTGS2, and RELA and high expression of PIK3CA had a significantly better prognosis than their counterparts. Further validation of gene expression by using GEPIA revealed that the mRNA expression of MMP9 was significantly lower in breast cancer tissues than in normal tissues, whereas the mRNA expression of PTGS2 showed the opposite. Analysis with ONCOMINE demonstrated that the mRNA expression levels of MMP9 and NFKB1 were significantly higher in metastatic breast cancer cells than in normal tissues. The results of molecular docking analyses revealed the advantage of tangeretin as an inhibitor of PIK3CA, MMP9, PTGS2, and IKK.Conclusion: Tangeretin inhibits metastasis in breast cancer cells by targeting TP53, PTGS2, MMP9, and PIK3CA and regulating the PI3K/Akt signaling pathway. Further investigation is needed to validate the results of this study.

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“…Somatic mutations in the TP53 gene encoding tumor protein p53 are one of the most common genetic abnormalities associated with human cancer and have been implicated as causal events in up to 50% of all human malignancies. Germline TP53 mutations also increase the risk of numerous neoplasm types, including breast cancer, leukemia, sarcomas, and central nervous system tumors [5].…”

Section: Discussionmentioning

confidence: 99%

“…TP53 is a tumor suppressor gene located on chromosome 17p13.1 that encodes protein p53. The tumor protein p53 binds directly to DNA and participates in the regulation of cell cycle checkpoints, DNA repair, and apoptosis and regulates the repair process in response to damaging factors, including chemicals, radiation, and ultraviolet rays from sunlight [5]. It has been reported that rs1042522 (c.215G>C, p.Arg72Pro) and rs17878362 (16-bp insertion/duplication in intron 3), two most frequently analyzed TP53 polymorphisms, may affect either the function of the p53 protein or its mRNA expression [6–8].…”

Section: Introductionmentioning

confidence: 99%

Two Functional TP53 Genetic Variants and Predisposition to Keloid Scarring in Caucasians

Dmytrzak¹,

Boroń

Łoniewska

et al. 2019

Dermatology Research and Practice

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Introduction Keloid is defined as a benign proliferative scar that grows beyond the confines of the original insult to the skin, invading into adjacent normal tissue. The pathogenesis of keloid is complex, and many evidences suggest the influence of genetic factors, among them the polymorphisms of the TP53 gene encoding tumor protein p53. Objective To investigate the association of rs1042522 (c.215G>C, p.Arg72Pro) and rs17878362 (16-bp insertion/duplication in intron 3) variants, two most frequently analyzed TP53 functional polymorphisms and the risk of keloid in Polish patients. Materials and Methods The rs1042522 and rs17878362 polymorphisms were identified by sequencing genomic DNA extracted from peripheral blood leukocytes of 86 keloid patients and from cordial blood leukocytes of 100 newborn infants consisting control group. Results The rs1042522 and rs17878362 TP53 genotype distributions both in keloid patients and in the control group conformed to the expected Hardy–Weinberg equilibrium. No significant differences in the distribution of rs1042522 and rs17878362 TP53 alleles or genotypes have been found between keloid patients and newborn controls. There is tight, but not complete, linkage disequilibrium between rs1042522 and rs17878362 TP53 polymorphisms (D′ = 0.667, r = 0.448, and p=0). No significant differences in the distribution of rs1042522 and rs17878362 TP53 haplotypes or diplotypes have been found between keloid patients and newborn controls. Conclusions Our results suggest the lack of association of rs1042522 and rs17878362 TP53 polymorphisms and their haplotypes or diplotypes with the susceptibility to keloid scarring in Polish patients.

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TP53 mutations and SNPs as prognostic and predictive factors in patients with breast cancer (Review)

Cited by 40 publications

References 62 publications

A TP53 -associated gene signature for prediction of prognosis and therapeutic responses in lung squamous cell carcinoma

A TP53 -associated gene signature for prediction of prognosis and therapeutic responses in lung squamous cell carcinoma

Integrative Bioinformatics Study Reveals Tangeretin Targets and Molecular Mechanisms Against Metastatic Breast Cancer

Two Functional TP53 Genetic Variants and Predisposition to Keloid Scarring in Caucasians

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