Serum miR-373-3p and miR-194-5p Are Associated with Early Tumor Progression during FOLFIRINOX Treatment in Pancreatic Cancer Patients: A Prospective Multicenter Study

Abstract

In this study, we explored the predictive value of serum microRNA (miRNA) expression for early tumor progression during FOLFIRINOX chemotherapy and its association with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). A total of 132 PDAC patients of all disease stages were included in this study, of whom 25% showed progressive disease during FOLFIRINOX according to the RECIST criteria. MiRNA expression was analyzed in serum collected before the start and after one cycle of chemotherapy. In the discovery cohort (n = 12), a 352-miRNA RT-qPCR panel was used. In the validation cohorts (total n = 120), miRNA expression was detected using individual RT-qPCR miRNA primers. Before the start of FOLFIRINOX, serum miR-373-3p expression was higher in patients with progressive disease compared to patients with disease control after FOLFIRINOX (Log2 fold difference (FD) 0.88, p = 0.006). MiR-194-5p expression after one cycle of FOLFIRINOX was lower in patients with progressive disease (Log2 FD −0.29, p = 0.044). Both miRNAs were predictors of early tumor progression in a multivariable model including disease stage and baseline CA19-9 level (miR-373-3p odds ratio (OR) 3.99, 95% CI 1.10–14.49; miR-194-5p OR 0.91, 95% CI 0.83–0.99). MiR-373-3p and miR-194-5p did not show an association with OS after adjustment for disease stage, baseline CA19-9, and chemotherapy response. In conclusion, high serum miR-373-3p before the start and low serum miR-194-5p after one cycle are associated with early tumor progression during FOLFIRINOX.

Clinical Value of Circulating miRNA in Diagnosis, Prognosis, Screening and Monitoring Therapy of Pancreatic Ductal Adenocarcinoma–A Review of the Literature

“…This may also influence the decision to discontinue the therapy in patients who will no longer benefit from treatment. Studies included in this review provide data on this matter [ 46 , 83 , 84 , 85 , 87 , 88 ]. However, many factors contribute to the choice of therapy and the most significant of them is the patient’s performance status (PS) before the start of the treatment.…”

“…We investigated 21 studies on the prognostic value of miRNA [ 28 , 32 , 35 , 36 , 37 , 46 , 48 , 52 , 53 , 61 , 64 , 65 , 66 , 72 , 74 , 80 , 81 , 82 , 83 , 84 , 85 ]. The prognostic value of different miRNAs was evaluated 30 times.…”

“…The predictive value of circulating miRNA was evaluated in six studies covered here [ 46 , 83 , 84 , 85 , 87 , 88 ]. In a study by Miyamae et al [ 53 ], an increased expression of plasma miR-744 indicated the tendency to worse PFS during gemcitabine therapy ( p = 0.0533).…”

“…Wang et al [ 85 ] presented similar results for serum miR-21, the over-expression of which indicated a shortened time to progression (TTP) and overall survival (OS) among patients with PDAC stage III and IV during gemcitabine therapy ( p = 0.029 for OS, CS III; p = 0.069 for OS, CS IV; p = 0.008 for TTP, CS III; p = 0.029 for TTP, CS IV). In a study by van der Sijde et al [ 84 ], a high level of serum miR-373-3p before the start of treatment and a low level of serum miR-194-5p after one cycle of treatment were associated with early tumor progression during FOLFIRINOX therapy. In a study Demiray et al [ 88 ], patients with low let-7c expression progressed significantly earlier than patients with high let-7c expression during FOLFIRINOX therapy.…”

Circulating Cell-Free Nucleic Acids as Biomarkers for Diagnosis and Prognosis of Pancreatic Cancer

“…Serum miR-373-3p was highly expressed in PDAC patients with progressive disease before the start of FOLFIRINOX and serum miR-194-5p expression was decreased after one cycle of FOLFIRINOX, compared to healthy controls; both miRNAs were significant predictors of early tumor progression during FOLFIRINOX [ 135 ].…”