Liquid biopsy leads to a paradigm shift in the treatment of pancreatic cancer

Table 4 Liquid biopsy in the therapeutic effect monitoring of pancreatic cancer

Ref.	Journal	No. of patients	Biomarker	Method	Main findings
Del Re et al[133], 2017	Sci Rep	27	ctDNA	ddPCR	There was a statistically significant difference in PFS and OS in patients with increase vs stability/reduction of ctDNA in the sample collected at day 15 (P = 0.03 and P = 0.009, respectively)
Kruger et al[134], 2018	Ann Oncol	54	ctDNA	BEAMing	An increase in ctDNA at day 14 correlated with disease progression on subsequent imaging with a sensitivity of 83% and specificity of 100%
Watanabe et al[98], 2019	PLoS One	39	ctDNA	ddPCR	The emergence of KRAS ctDNA in longitudinal tests was associated with prognosis (P < 0.005)
Wei et al[135], 2019	Cancer Lett	13 (chemotherapy group)	CTC	Vimentin or EpCAM immobilized microfluidic chip	In patients exhibiting a response, their CTC counts decreased or remained the same, except for one case
Okubo et al[108], 2017	Eur J Surg Oncol	65	CTC	Cellsearch	The overall survival rate was significantly lower in patients with than in those without CTCs even after chemotherapy and chemoradiotherapy (P = 0.045)
Xu et al[78], 2017	Int J Mol Sci	83	CTC	NE-iFISH	The proportion of triploid CTC detected by the NE-iFISH was significantly decreased after chemotherapy (P < 0.001)
Tian et al[136], 2016	Oncol Lett	17	microRNA	RT-qPCR	Significant upregulation of serum miRNAs (miR-21, miR-210, miR-221 and miR-7), at earlier time points (3-6 wk) was observed in non-responders of chemotherapy compared to responders
Bernard et al[99], 2019	Gastroenterology	104 (chemotherapy group)	exosome and ctDNA	ddPCR	In the longitudinal analysis in chemotherapy group, a MAF peak above 1% in exosome DNA was significantly associated with radiologic progression (P = 0.0003)
An et al[137], 2017	J Proteome Res	10	exosome	iTRAQ	They analyzed exosomes before treatment, after one cycle of induction gemcitabine-based chemotherapy, and at 3 wk after starting chemoradiation therapy and compared these samples to serum derived from healthy volunteers. They identified eight proteins that changed during a course of therapy in all patients
Liang et al[84], 2017	Nat Biomed Eng	23 (neoadjuvant chemotherapy group)	EV	nPES	EphA2-EVs were also informative in detecting early responses to neoadjuvant therapy (P < 0.05)
Yin et al[138], 2021	Clin Cancer Res	36	somatic mutations, CTCs, and ctDNA	Next-generation sequencing & ISET	Somatic mutations, CTCs, and ctDNA existed even in patients with PDAC with pathologic complete response to NAT, which could possibly predict early recurrence and reduced survival
Poruk et al[140], 2016	Ann Surg	50	CTC	ISET	The detection of CTCs expressing both vimentin and cytokeratin was predictive of recurrence (P = 0.01)
Gemenetzis et al[139], 2018	Ann Surg	57	CTC	ISET	Patients who received neoadjuvant chemotherapy had significantly lower total CTCs (tCTCs, P = 0.007), eCTCs (P = 0.007), and mCTCs (P = 0.034), compared with untreated patients eligible for upfront resection

ctDNA: Circulating tumor DNA; CTC: Circulating tumor cell; CR: Complete response; ddPCR: Droplet digital polymerase chain reaction; eCTCs: Epithelial circulating tumor cell; EpCAM: Epithelial cell adhesion molecule; EphA2: Ephrin type-A receptor 2; EV: Extracellular vesicles; iTRAQ: Isobaric tag for relative and absolute quantitation; ISET: Isolation by size of epithelial tumor cells; MAF: Mutant allele frequency; mCTCs: Mesenchymal circulating tumor cell; nPES: Nanoplasm-enhanced scattering; NAT: Neoadjuvant chemotherapy; NE-iFISH: Negative enrichment immunofluorescence and in situ hybridization of chromosome 8; OS: Overall survival; PFS: Progression-free survival; RT-qPCR: Quantitative reverse transcription polymerase chain reaction; tCTC: Total circulating tumor cell.