Inflammation and cancer

Mariko Murata, Mariko Murata

Abstract

Infection and inflammation account for approximately 25% of cancer-causing factors. Inflammation-related cancers are characterized by mutagenic DNA lesions, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine. Our previous studies demonstrated the formation of 8-oxodG and 8-nitroguanine in the tissues of cancer and precancerous lesions due to infection (e.g., Opisthorchis viverrini-related cholangiocarcinoma, Schistosoma haematobium-associated bladder cancer, Helicobacter pylori-infected gastric cancer, human papillomavirus-related cervical cancer, Epstein-Barr virus-infected nasopharyngeal carcinoma) and pro-inflammatory factors (e.g., asbestos, nanomaterials, and inflammatory diseases such as Barrett's esophagus and oral leukoplakia). Interestingly, several of our studies suggested that inflammation-associated DNA damage in cancer stem-like cells leads to cancer development with aggressive clinical features. Reactive oxygen/nitrogen species from inflammation damage not only DNA but also other biomacromolecules, such as proteins and lipids, resulting in their dysfunction. We identified oxidatively damaged proteins in cancer tissues by 2D Oxyblot followed by MALDI-TOF/TOF. As an example, oxidatively damaged transferrin released iron ion, which may mediate Fenton reactions and generate additional reactive oxygen species. Dysfunction of anti-oxidative proteins due to this damage might increase oxidative stress. Such damage in biomacromolecules may form a vicious cycle of oxidative stress, leading to cancer development. Epigenetic alterations such as DNA methylation and microRNA dysregulation play vital roles in carcinogenesis, especially in inflammation-related cancers. We examined epigenetic alterations, DNA methylation and microRNA dysregulation, in Epstein-Barr virus-related nasopharyngeal carcinoma in the endemic area of Southern China and found several differentially methylated tumor suppressor gene candidates by using a next-generation sequencer. Among these candidates, we revealed higher methylation rates of RAS-like estrogen-regulated growth inhibitor (RERG) in biopsy specimens of nasopharyngeal carcinoma more conveniently by using restriction enzyme-based real-time PCR. This result may help to improve cancer screening strategies. We profiled microRNAs of nasopharyngeal carcinoma tissues using microarrays. Quantitative RT-PCR analysis confirmed the concordant downregulation of miR-497 in cancer tissues and plasma, suggesting that plasma miR-497 could be used as a diagnostic biomarker for nasopharyngeal carcinoma. Chronic inflammation promotes genetic and epigenetic aberrations, with various pathogeneses. These changes may be useful biomarkers in liquid biopsy for early detection and prevention of cancer.

Keywords: Cancer; DNA damage; DNA methylation; Inflammation; Liquid biopsy; MicroRNA; Reactive oxygen/nitrogen species.

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The author declares that she has no competing interests.

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Figures

Fig. 1
Fig. 1
Biomacromolecule damage by inflammation
Fig. 2
Fig. 2
Epigenetic alterations under an inflammatory microenvironment. White circles indicate unmethylated CpG sites, and black circles show methylated CpG sites in the promoter region
Fig. 3
Fig. 3
Liquid biopsy and multistage carcinogenesis

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