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.
Highlights
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the US, and the number of deaths continues to increase in T aiwan[1,2]
ferritin light polypeptide (FTL), on the other hand, displayed significant positive correlations with ALOX15 (r = 0.893; p = 0.0005), FDFT1 (r = 0.761; p = 0.0106), RPL8 (r = 0.689; p = 0.0274), and TP53 (r = 0.893; p = 0.0005) in the control group, whereas it was strongly negatively correlated with ALOX15 (G1; r = − 0.747; p = 0.131), CBS (G3; r = − 0.689; p = 0.0092), FDFT1 (G3; r = − 0.595; p = 0.0321), TP53 (G1; r = − 0.738; p = 0.0148) and TTC35 (G2; r = − 0.381; p = 0.0457) in pancreatic tumor tissues (Table 2). These results indicated that correlations of gene expressions of ferritin high polypeptide 1 (FTH1) or FTL with the majority of ferroptotic genes in a set were reversed with pancreatic tumors, suggesting that FTH1 and FTL ferritin subunits may interact with key ferroptosis regulators to mediate ferroptosis in pancreatic cancer patients
We found that high serum ferritin (SF) was associated with increasing risks of pancreatic cancer; SF has potential application as a clinical biomarker in the diagnosis of pancreatic cancer
Summary
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the US, and the number of deaths continues to increase in T aiwan[1,2]. As high levels of iron are potentially toxic, several epidemiological studies found associations between high levels of SF and increased risks for various cancers, suggesting that SF could be used as an iron index and a tumor marker[13,14,15,16]. We performed a pooled analysis of six studies for a comprehensive quantitative assessment of the association of SF levels with pancreatic cancer risks. An Oncomine database analysis of patient-derived gene expressions was used to assess potential genes that might mediate the association between ferritin and pancreatic cancer. SF levels could serve as a potential marker to predict individuals at increased risk during pancreatic cancer screening, along with being a novel therapeutic strategy for pancreatic cancer
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