Overexpression of folate receptor alpha is an independent prognostic factor for outcomes of pancreatic cancer patients

Abstract

Pancreatic cancer has a poor prognosis; hence, novel prognostic markers and effective therapeutic targets should be identified. We aimed to evaluate folate receptor alpha (FR-α) expression in pancreatic cancer and examine its association with clinicopathological features. We utilized tissue samples from 100 primary pancreatic cancer patients who underwent surgery. FR-α was expressed in 37 of 100 cases (37%). The FR-α-positive group (median, 18.8 months) had a significantly poorer prognosis than the FR-α-negative group [median 21.3 months; HR 1.89 (1.12-3.12); P = 0.017]. These groups were not significantly different regarding progression-free survival (P = 0.196). Furthermore, other serum tumor markers including CA19-9 (mean, 186 vs. 822 U/ml; P = 0.001), Dupan-2 (286 vs. 1133 U/ml; P = 0.000), and Span-1 (69.7 vs. 171.9 U/ml; P = 0.006) were significantly downregulated in the FR-α-positive group. CA19-9 was another prognostic factor, in addition to FR-α, and patient prognosis showed clear stratification curves with the expression of these two molecules. Along with CA19-9, FR-α expression was an independent prognostic factor for the overall survival. FR-α and CA19-9 helped predict patient prognosis based on stratification curves.

Development of a novel multi-functional integrated bioconjugate effectively targeting K-Ras mutant pancreatic cancer

“…FRα has been found in pancreatic cancer, breast cancer, ovarian cancer, head and neck cancer, lung cancer, bladder cancer, kidney cancer, and colon cancer. Approximately 40% of human cancers overexpress FR [ 34 , 35 ]. A previous study using immunohistochemical analysis showed that in 22 (16%), 73 (52%) and 45 (32%) specimens of 140 PDAC patients, FRα expression intensity was low, moderate, and high, respectively [ 36 ].…”

“…A previous study using immunohistochemical analysis showed that in 22 (16%), 73 (52%) and 45 (32%) specimens of 140 PDAC patients, FRα expression intensity was low, moderate, and high, respectively [ 36 ]. From the database of Encyclopedia of Cancer Cell Lines, at the mRNA level, FRα is highly expressed in pancreatic cancer after breast cancer according to the incidence rate [ 35 ]. Therefore, folate binding is a potential method to target FR-positive tumor tissues for personalized treatment.…”

Investigation of Serum Folate-Receptor-1 Levels in Patients with Non-Small Cell Lung Cancer

“…Histopathological FOLR1 (FRα gene) mRNA expression has been reported to be significantly higher in cancers such as mesothelioma, lung, pancreas, ovarian, and colorectal cancers (8)(9)(10)(11). Over-expression histopathological FRα has been reported in adenocarcinoma compared to squamous cell cancers (7,20).…”

“…Histopathological overexpressed FOLR1 in various solid tumors such as breast, ovarian, pancreatic, kidney, and lung cancer, especially NSCLC and high-grade osteosarcoma, was caused by the increased metabolic needs of folates to feed nucleic acid synthesis and cellular growth (5)(6)(7)(8)(9)(10)(11). FOLR1 could be transferred from the localized cell surface to the bloodstream as a soluble form of sFOLR1 (12,13).…”

A preliminary study of the clinical significance of folate receptor- positive circulating tumor cell in the management of hepatobiliary- pancreatic cancers

“…PCR is performed to amplify the oligonucleotide bound to the FRα on the CTCs and enhance the detection sensitivity (18). Although FRα was also found to be expressed in tumor tissues of hepatobiliary cancers and pancreatic cancers (32)(33)(34)(35)(36), the clinical utility of FR+CTC in these types of cancer remains to be examined. Hence, in this preliminary study, we aimed to explore the clinical significance of FR+CTC in the differential diagnosis and management of HBPs.…”