Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma

Abstract

Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer and is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood. However, genes encoding chromatin remodeling enzymes are frequently mutated in OAC. This is consistent with the emerging concept that cancer cells exhibit reprogramming of their chromatin environment which leads to subsequent changes in their transcriptional profile. Here, we have used ATAC-seq to interrogate the chromatin changes that occur in OAC using both cell lines and patient-derived material. We demonstrate that there are substantial changes in the regulatory chromatin environment in the cancer cells and using this data we have uncovered an important role for ETS and AP1 transcription factors in driving the changes in gene expression found in OAC cells.

Decoding genetic and epigenetic information embedded in cell free DNA with adapted SALP‐seq

“…Gene dysregulation is a hallmark of cancers . An open chromatin profile study revealed that there are substantial changes in the regulatory chromatin environment in the cancer cells and uncovered an important role for ETS and AP1 TFs in driving the changes in gene expression found in oesophageal adenocarcinoma cells . In this cfDNA study, we also demonstrate that the chromatin openness state of EC patients differs from that of healthy people.…”

“…For this reason, the length of cancer patient cfDNA is shorter than that of healthy people. Other study also revealed that the chromatin state is more open in esophagus cancer cell lines than in normal cell lines …”

“…Other study also revealed that the chromatin state is more open in esophagus cancer cell lines than in normal cell lines. 23 The GC content can usually be used as an indicator of DNA change. This study showed that the EC cfDNA has lower GC content than that of healthy people.…”

“…The five‐years survival rates of EC remain less than 20% . However, due to the poor prognosis and late clinical presentation for patients with EC, the knowledge of biomarkers and potential therapeutic targets is limited . For these reasons, new approach to diagnose for EC is needed urgently.…”

“…22 However, due to the poor prognosis and late clinical presentation for patients with EC, the knowledge of biomarkers and potential therapeutic targets is limited. 23 For these reasons, new approach to diagnose for EC is needed urgently. With the adapted SALP-seq, we constructed the NGS libraries with 20 plasma cfDNA samples from 11 preoperation EC patients, 5 postoperation EC patients and 4 healthy people.…”