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DNA Repair Biomarker for Lung Cancer Risk and its Correlation With Airway Cells Gene Expression.

ABSTRACT: Background:Improving lung cancer risk assessment is required because current early-detection screening criteria miss most cases. We therefore examined the utility for lung cancer risk assessment of a DNA Repair score obtained from OGG1, MPG, and APE1 blood tests. In addition, we examined the relationship between the level of DNA repair and global gene expression. Methods:We conducted a blinded case-control study with 150 non-small cell lung cancer case patients and 143 control individuals. DNA Repair activity was measured in peripheral blood mononuclear cells, and the transcriptome of nasal and bronchial cells was determined by RNA sequencing. A combined DNA Repair score was formed using logistic regression, and its correlation with disease was assessed using cross-validation; correlation of expression to DNA Repair was analyzed using Gene Ontology enrichment. Results:DNA Repair score was lower in case patients than in control individuals, regardless of the case's disease stage. Individuals at the lowest tertile of DNA Repair score had an increased risk of lung cancer compared to individuals at the highest tertile, with an odds ratio (OR)?of 7.2 (95% confidence interval [CI] = 3.0 to 17.5; P?

SUBMITTER: Paz-Elizur T

PROVIDER: S-EPMC7012022 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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DNA Repair Biomarker for Lung Cancer Risk and its Correlation With Airway Cells Gene Expression.

Paz-Elizur Tamar T Leitner-Dagan Yael Y Meyer Kerstin B KB Markus Barak B Giorgi Federico M FM O'Reilly Martin M Kim Hyunjin H Evgy Yentl Y Fluss Ronen R Freedman Laurence S LS Rintoul Robert C RC Ponder Bruce B Livneh Zvi Z

JNCI cancer spectrum 20190912 1

<h4>Background</h4>Improving lung cancer risk assessment is required because current early-detection screening criteria miss most cases. We therefore examined the utility for lung cancer risk assessment of a DNA Repair score obtained from OGG1, MPG, and APE1 blood tests. In addition, we examined the relationship between the level of DNA repair and global gene expression.<h4>Methods</h4>We conducted a blinded case-control study with 150 non-small cell lung cancer case patients and 143 control ind ...[more]

PMID: 32064457

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Project description:IntroductionMany studies have reported that human-induced pluripotent stem (hiPS)/embryonic stem (hES) cells have an exceptional ability to repair damaged DNA. Moreover, unlike differentiated cells, hES cells have features and mechanisms such as apoptosis-prone mitochondria, which prevent any changes in genetic information caused by DNA damage to be transmitted to their descendants. Type-A (dark) spermatogonia and cancer stem cells are thought to be dormant. However, hiPS/hES cells, the so-called stem cells used in regenerative medicine, generally have a high proliferative capacity. This suggests that in these cells, oxidative DNA damage associated with vigorous proliferation and DNA scission associated with replication occur frequently. Although pluripotency according to change of genomic structure is well studied, the change of DNA repair through reprogramming has not been well studied.MethodsWe analyzed the expression of DNA repair-related genes in hiPS cells using microarray and western blotting analyses and assessed changes in PARP activity through reprogramming.ResultsThrough reprogramming, hiPS cells were found to upregulate poly (ADP-ribose) polymerase (PARP) activity and genes regulating homologous recombination (HR). Simultaneously, the expression level of genes involved in non-homologous end joining (NHEJ) was not high, suggesting that at least at the gene expression level, frequently occurring DNA scission is preferentially dealt with via HR instead of NHEJ. Also, reflecting the high proliferative activity, genes related to mismatch repair (MMR) were upregulated through reprogramming. Conversely, error-prone polymerase was downregulated through reprogramming. These are also likely to be the mechanisms preventing changes in genetic information.ConclusionsHigh PARP activity and HR-related gene expression in hiPS cells were achieved through reprogramming and likely facilitate precise genome editing in these cells in exchange for a high possibility of cell death.

Dataset Information

DNA Repair Biomarker for Lung Cancer Risk and its Correlation With Airway Cells Gene Expression.

Publications

DNA Repair Biomarker for Lung Cancer Risk and its Correlation With Airway Cells Gene Expression.

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