Association between DNA mismatch repair gene polymorphisms and platinum-based chemotherapy toxicity in non-small cell lung cancer patients

Liu, Junyan; Qian, Chenyue; Gao, Yuanfeng; Chen, Juan; Zhou, Hong‐Hao; Yin, Ji‐Ye

doi:10.1186/s40880-016-0175-2

Cited by 16 publications

(14 citation statements)

References 31 publications

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“…Therefore, several studies have focused on the assessment of the MMR status, as this may have a significant predictive value for these patients. [23,24,34,36,37].A number of regulatory molecules such as miRNAs have been suggested to be implicated in the regulation of MMR genes [38][39][40][41][42][43][44][45][46]. In particular, recent studies support a cross-talk between specific miRNAs and MMR genes [41][42][43].…”

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confidence: 99%

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The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

Doukas

Vageli²,

Lazopoulos

et al. 2020

Cells

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Tobacco smoking is a common risk factor for lung cancer and head and neck cancer. Molecular changes such as deregulation of miRNA expression have been linked to tobacco smoking in both types of cancer. Dysfunction of the Mismatch DNA repair (MMR) mechanism has also been associated with a poor prognosis of these cancers, while a cross-talk between specific miRNAs and MMR genes has been previously proposed. We hypothesized that exposure of lung and head and neck squamous cancer cells (NCI and FaDu, respectively) to tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is capable of altering the expression of MSH2 and MLH1, key MMR components, by promoting specific miRNA deregulation. We found that either a low (1 µM) or high (2 µM) dose of NNK induced significant upregulation of "oncomirs" miR-21 and miR-155 and downregulation of "tumor suppressor" miR-422a, as well as the reduction of MMR protein and mRNA expression, in NCI and FaDu, compared to controls. Inhibition of miR-21 restored the NNK-induced reduced MSH2 phenotype in both NCI and FaDu, indicating that miR-21 might contribute to MSH2 regulation. Finally, NNK exposure increased NCI and FaDu survival, promoting cancer cell progression. We provide novel findings that deregulated miR-21, miR-155, and miR-422a and MMR gene expression patterns may be valuable biomarkers for lung and head and neck squamous cell cancer progression in smokers.Cells 2020, 9, 1031 2 of 22 and neck squamous cell carcinoma (HNSCC), represents one of the most aggressive malignancies with a high rate of mortality. [8,9]. Tobacco smoking has been one of the most well-established risk factors for both lung and head and neck cancers [1][2][3][4][5][6][7][8]. It is known that tobacco smoke contains a mixture of thousands of compounds, including a large number of known carcinogens [2]. It is believed that exposure of cells to tobacco smoke carcinogens can lead to DNA damage, which may cause chromosomal instability and increased cell proliferation [10][11][12][13]. In particular, tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which is one of the chemicals in tobacco smoke, has been linked to lung and head and neck cancer [14], and has also been shown to upregulate oncogenic pathways [15][16][17].The development and progression of lung and head and neck malignancies appear to be a complex process. Although multiple diagnostic and prognostic markers have been identified for both lung and head and neck cancers [18,19], the precise molecular mechanisms involved in the development and progression of these malignancies remain unclear.We understand that a functional DNA repair mechanism that includes the recognition and repair of mismatch DNA errors during DNA replication is essential in eliminating the harmful effect of several environmental risk factors, such as NNK, on the exposed cells [20][21][22][23]. A number of studies have shown that reduced expression of mismatch DNA repair (MMR) genes increases the incidence of microsatellite ...

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mentioning

confidence: 99%

“…Therefore, several studies have focused on the assessment of the MMR status, as this may have a significant predictive value for these patients. [23,24,34,36,37].…”

mentioning

confidence: 99%

The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

Doukas

Vageli²,

Lazopoulos

et al. 2020

Cells

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“…Therefore, MutSα and MutLα are important proteins in the MMR system and are used to cooperate the mismatch detection and repair events. In previous study, we found that MutSα and MutLα genes were associated with the toxicity of platinum-based chemotherapeutic in lung cancer [30,31].…”

Section: Ivyspringmentioning

confidence: 93%

“…Finally, Thirty-five SNPs were genotyped in the patients (Table 1). In our previous studies, the SNPs were investigated to be associated with platinum-based chemotherapy toxicity [30].…”

Section: Snp Selection Dna Extraction and Genotypingmentioning

confidence: 99%

Genetic Variants in DNA Mismatch Repair Pathway predict prognosis of Lung Cancer patients with receiving Platinum-Based Chemotherapy

Liu¹,

Zou²,

Yin³

et al. 2020

J. Cancer

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Objective: To investigate the relationships between genetic variants in DNA mismatch repair pathway genes and the prognosis of platinum-based chemotherapy in lung cancer patients. Methods: 346 lung cancer patients who received at least two cycles of platinum-based chemotherapy were recruited in this study. A total of 35 single nucleotide polymorphisms in 7 DNA mismatch repair genes were genotyped to investigate their associations with platinum-based chemotherapy prognosis. Result: The results revealed that patients carried MSH2 rs4608577 TT genotype had a significantly shorter progression free survival than patients with GG or GT genotypes (Additive model: P=0.003, OR =0.94, 95% CI =0.33-1.57). Patients with SAPCD1 rs707937 TT genotype had a significantly longer overall survival than patients with GG or GT genotypes (Additive model: P=0.0003, OR=0.75, 95% CI =0.35-1.14). Eight SNPs and fourteen SNPs were related to progression free survival and overall survival in subgroup analyses, respectively. Conclusion: Our findings suggest that the MSH2 rs4608577 and SAPCD1 rs707937 may be potential clinical biomarkers for predicting platinum-based chemotherapy prognosis in lung cancer patients.

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“…Many studies suggested that MMR genes played important roles in chemotherapy. [49][50][51][52] Is this mutation important for the prediction of chemotherapy? Considering that the proband's chemotherapy regimen is oxaliplatin and 5-fu, and irinotecan is a commonly used chemotherapy drug for colorectal cancer, we use these three drugs for cell viability experiments.…”

Section: The Frameshift Mutation Was Found In All Cancer Diagnosed Mementioning

confidence: 99%

<p>A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family</p>

Shao

Wang

et al. 2020

CMAR

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In order to clarify which variants of the MMR gene could provide current "healthy" members in affected families a more accurate risk assessment or predictive testing. Patients and Methods: One family, which meets the criteria according to both Amsterdam I/II and Bethesda guidelines, is reported in this study. The proband and some relatives of the patient have been investigated for whole genome sequencing, microsatellite instability, immunohistochemical MMR protein staining and verified by Sanger sequencing. Results: A heterozygous insertion of uncertain significance (c.420dup, p.Met141Tyrfs) in MSH2 gene was found in proband (III-16) and part of His relatives. The variant was associated with a lack of expression of MSH2 protein (MMR deficient) and high microsatellite instability analysis (MSI) status in tumor tissues of LS patients. In addition, we found that the variant could affect the expression of MSH2 and the response to chemotherapy drugs in vitro. Conclusion: We identified an insertion mutation (rs1114167810, c.420dup, p.Met141Tyrfs) in MSH2 in LS using whole genome-wide sequencing (WGS). We further confirmed that this mutation plays an important role in LS patients of this pedigree based on in vivo and vitro study.

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Association between DNA mismatch repair gene polymorphisms and platinum-based chemotherapy toxicity in non-small cell lung cancer patients

Cited by 16 publications

References 31 publications

The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

Genetic Variants in DNA Mismatch Repair Pathway predict prognosis of Lung Cancer patients with receiving Platinum-Based Chemotherapy

<p>A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family</p>

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