A case–control study in Taiwanese cohort and meta-analysis of serum ferritin in pancreatic cancer

Abstract

Pancreatic cancer is one of the most lethal diseases which lack an early diagnostic marker. We investigated whether serum ferritin (SF) reflects risk for pancreatic cancer and potential genes that may contribute ferritin and pancreatic cancer risks. We performed a meta-analysis of relevant studies on SF and pancreatic cancer risk by searching articles in PUBMED and EMBASE published up to 1 March 2020. We also collected serum samples from Taipei Medical University Joint Biobank and compared SF levels in 34 healthy controls and 34 pancreatic cancer patients. An Oncomine database was applied as a platform to explore a series of genes that exhibited strong associations between ferritin and pancreatic cancer. Herein, we show that high levels of SF can indicate risk of pancreatic cancer, suggesting SF as the new tumor marker that may be used to help pancreatic cancer diagnosis. We also found that expressions of iron homeostasis genes (MYC, FXN) and ferroptosis genes (ALOX15, CBS, FDFT1, LPCAT3, RPL8, TP53, TTC35) are significantly altered with pancreatic tumor grades, which may contribute to differential expression of ferritin related to pancreatic cancer prognosis.

Iron overload phenotypes and HFE genotypes in white hemochromatosis and iron overload screening study participants without HFE p.C282Y/p.C282Y

“…Our study design excluded non-Hispanic white CE participants who may have had elevated SF and elevated TS due to types of anemia that increase iron absorption, a history of erythrocyte transfusion >10 units, viral hepatitis B or C, or increased alcohol intake. Elevated SF without elevated TS is common in patients with obesity [ 15 ], metabolic syndrome [ 16 ], diabetes [ 17 ], non-alcoholic fatty liver disease [ 18 , 19 ], inflammatory disorders [ 16 ], malignancies [ 20 – 22 ], "classic" ferroportin hemochromatosis due to deleterious SLC40A1 alleles [ 16 ], hereditary hyperferritinemia-cataract syndrome [ 16 ], and benign autosomal dominant hyperferritinemia [ 23 ]. Thus, our selection criteria also excluded participants who had elevated SF without elevated TS due to these or other conditions.…”

The Role of Ferritin in Health and Disease: Recent Advances and Understandings

“…In contrast to hypoxic induction of ferritinophagy in the liver and the intestine [ 46 , 47 ], hypoxia increases ferritin expression in primary human macrophages via miRNA-mediated ferritinophagy inhibition and protects the cells from ferroptosis [ 66 ]. Several clinical studies suggest that high ferritin levels and altered ferroptosis gene expression are associated with poor prognosis of malignant and neurodegenerative disorders [ 67 , 68 , 69 ]. In addition, modulation of ferritinophagy to regulate cellular ferroptosis sensitivity offers novel avenues for cancer, cardiovascular and metabolic disorder management [ 70 , 71 , 72 ].…”

Molecular subtypes based on cell death genes predict prognosis and immunotherapy effect in patients with hepatocellular carcinoma

“…Ribosomal protein L8 (RPL8), a component protein of the eukaryotic ribosomal subunit, inhibits Erastin-induced ferroptosis [34 ]. Studies have con rmed that the expression of RPL8 was signi cantly increased in advanced pancreatic tumor tissues, which enhanced the invasiveness of pancreatic cancer cells and inhibited the ferroptosis effect of pancreatic cancer cells, and was an important negative regulator of pancreatic cancer [35]. However, no reports have been reported on the relationship between RPL8 gene expression and the occurrence and development of HCC.…”