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Tobacco smoking is a major driver of head and neck squamous cell carcinoma (HNSCC) occurrence, and previous studies have shed light on the precise molecular alterations in tobacco-related HNSCCs when compared to HNSCCs associated with other risk factors (ex: human papillomavirus/HPV status). In this study, we analyzed the gene expression differences in HNSCC cases with a recent smoking history and revealed that the nicotinic acetylcholine receptor CHRNA5 is differentially overexpressed in smoking-related HNSCCs. CHRNA5 overexpression in these HNSCCs corresponds with a worse prognosis and is inversely correlated with an immune expression signature commonly associated with better prognosis. From these results, our study highlights the potential role of the nicotine-activated CHRNA5 receptor in HNSCC progression and corresponds with other recent reports highlighting the potential role of nicotine induction in promoting cancer progression., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Previous studies showed that intratumoral 27-Hydroxycholesterol (27-HC), a metabolite of cholesterol, promotes growth, invasion and migration of breast cancer cells and that tumor-associated macrophages (TAMs) in breast cancers are closely related to tumor growth and metastatic progression. However, the relationship between 27-HC and TAMs in breast cancer remains unclear. In the present study, we observed that CYP27A1, the 27-HC synthesizing enzyme, was expressed in a much higher level in THP1 monocytes and THP1-derived macrophages than in breast cancer cells, and the promoter of CYP7B1 , the degrading enzyme for 27-HC, was highly methylated in breast tumor cells. In addition, THP-1 monocytes and murine bone marrow cells were differentiated toward M2 type macrophages after being co-cultured with breast cancer cells or being exposed to exosomes derived from breast cancer cells. M2 type macrophages produced higher amounts of 27-HC than M0 and M1 type macrophages. 27-HC not only stimulated ER+ cancer cell proliferation as reported, but also promoted the recruitment of CCR2- and CCR5-expressing monocytes by inducing macrophages to express multiple chemokines including CCL2, CCL3 and CCL4. Taken together, our data demonstrate that the hypermethylation of CYP7B1 and recruitment of monocytes likely contribute to the accumulation of 27-Hydroxycholesterol in breast cancer and that the interaction of 27-HC with macrophages further promote the development of breast cancer., Competing Interests: None., (AJCR Copyright © 2019.)

DNA methylation is the most studied epigenetic event in cancer, with focus being placed on studying the entire DNA methylation landscape in specific cancers. Due to the recent advances of next-generation sequencing technology, several effective methods have been developed for high-throughput analysis of DNA methylation, enabling DNA methylation markers to be innovative diagnostic and therapeutic strategies in cancer. In this review, we discuss various current and emerging technologies in DNA methylation analysis that integrate next-generation sequencing with the basic principles of methylation detections including methylation sensitive restriction enzyme digestion, affinity purification with antibody or binding proteins, and bisulfite treatment. Variations to these described methods have also allowed for detection of 5-hydroxymethylcytosine marks on a genome-wide scale. We also describe several of the bioinformatic tools used to properly analyze methylome-sequencing data. Finally, recently developed artificial transcription-factor (ATF) targeting tools may provide flexible manipulation of DNA methylation events in specific gene regions, revealing the functional consequences of particular DNA methylation events.