Figure 5
FGF5 methylation levels in normal esophageal tissues with different risk levels. (A) Deep bisulfite sequencing of normal esophageal mucosae from healthy people without exposure to lifestyle risk factors (low risk), normal esophageal mucosae from healthy people with exposure (intermediate risk), and non-cancerous esophageal mucosae of cancer patients, all of whom had exposure (high risk). The fraction of methylated DNA molecules increased according to the risk level. The position of the original consecutive CpG sites (cg10031614, cg12528713, and cg20528583) are marked by red arrowheads. (B) Fraction of densely methylated DNA molecules in normal esophageal tissues in the three risk groups. When 9 or more CpG sites were methylated among the 18 CpG site in a molecule, the molecule was counted as a densely methylated DNA molecule. The fraction of densely methylated DNA molecules significantly increased according to the increased risk level (Jonckheere-Terpstra trend test). (C) Expression levels of FGF5 and FGF5-S variants in non-cancerous esophageal surgical samples and two ESCC cell lines. Error bars mean SD (n = 3). (D) Model on the origin of FGF5 methylation and its role in the sensitivity to dCRT. After exposure to risk factors for ESCCs, aberrant methylation of multiple genes, including FGF5, creeps into esophageal mucosa. When an ESCC develops from a cell without FGF5 methylation, it is capable of expressing FGF5 upon dCRT and thus is resistant. When an ESCC happens to develop from a cell with FGF5 methylation, the ESCC cannot express FGF5 upon dCRT and becomes vulnerable to dCRT.
