Advances in pancreatic cancer epigenetics: From the mechanism to the clinic

Table 4 Epigenetic markers in treatment response monitoring

Epigenetic marker	Description	Impact on treatment response	Clinical relevance
SFRP1 methylation	Methylation of SFRP1 promoter is associated with poor treatment response and resistance to gemcitabine	Increased SFRP1 methylation linked to reduced sensitivity to chemotherapy drugs like gemcitabine	Potential biomarker for assessing chemotherapy resistance, especially in advanced PDAC
circFARP1	CircFARP1 is a CAF-specific circRNA positively correlated with gemcitabine resistance	Gemcitabine resistance observed in patients with high circFARP1 expression	Could guide personalized treatment strategies for patients showing gemcitabine resistance
circBIRC6	CircBIRC6, upregulated in CAF-derived EVs, correlates with oxaliplatin chemotherapy resistance	CircBIRC6 contributes to resistance against chemotherapy, especially oxaliplatin	Marker for predicting oxaliplatin resistance and helping in therapeutic planning
HOTAIR (lncRNA)	HOTAIR overexpression is linked to poor survival and chemotherapy resistance in advanced cancer stages	High expression correlates with poor response to therapy, particularly in advanced stages	Can be used to predict response to therapy in advanced pancreatic cancer
circFARP1 (hsa_circ_0002557)	High circFARP1 levels correlate with gemcitabine resistance and lower survival in advanced PDAC	CircFARP1 Levels predict resistance to gemcitabine and poor survival	Indicates poor prognosis, guiding clinicians in optimizing chemotherapy strategies
EZH2 (Histone Methyltransferase)	EZH2 overexpression in pancreatic cancer cells leads to chemotherapy resistance	EZH2 overexpression contributes to pancreatic cancer resistance to chemotherapy	Targeting EZH2 could enhance the efficacy of current chemotherapies.
HDAC1 & PRMT1	HDAC1 and PRMT1 are epigenetic regulators influencing drug resistance by modifying chromatin and gene expression	HDAC1 and PRMT1 modulation affect tumor cell resistance to chemotherapy and immunotherapy	Both are crucial in predicting and overcoming drug resistance in pancreatic cancer patients

PDAC: Pancreatic ductal adenocarcinoma; lncRNA: Long noncoding RNA.