Ferritin as an independent mortality predictor in patients with pancreas cancer. Results of a pilot study

Kalousová, Marta; Krechler, T; Jáchymová, M; Kubêna, Aleŝ; Žák, Aleš; Zima, Tomáš

doi:10.1007/s13277-012-0426-z

Cited by 46 publications

(41 citation statements)

References 16 publications

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“…Several forms of cancer including lung [17,18], pancreatic [19] colon [20][21][22][23], and breast cancer [20,[24][25][26][27] have been reported to exhibit significant levels of iron overload. Breast cancer cells have been shown to exhibit increased levels of hepcidin, ferritin, and labile iron along with decreased FPN expression [24].…”

Section: Introductionmentioning

confidence: 99%

Estrogen-Dependent Downregulation of Hepcidin Synthesis Induces Intracellular Iron Efflux in Cancer Cells In Vitro

Shafarin¹,

Bajbouj²,

Serafy³

et al. 2016

Biol Med (Aligarh)

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It is well accepted that intracellular iron overload that associate with various forms of cancer fuels tumor mutagenesis and growth. Hence, iron chelation therapy is being increasingly used to minimize iron overload in cancer patients despite significant safety and efficacy concerns. Mounting evidence suggests that estrogen (E2) downregulates hepcidin synthesis and increases serum iron concentration. It is postulated therefore that, by downregulating hepcidin synthesis, E2 may maintain ferroportin integrity and enhance intracellular iron efflux. Here, MCF-7 and SKOV-3 cancer cells treated with increasing concentrations (5, 10 and 20 nM) of E2 were assessed for intracellular labile iron content, the expression of hepcidin, ferroportin, and transferrin receptors 1 and 2 along with cell viability at different time points post treatment. In MCF-7 cells, E2 treatment resulted in a significant reduction in hepcidin synthesis, most noticeably at the 20 nM/24 h dose, a significant increase in ferroportin expression and a marked decrease in transferrin receptors 1 and 2 expression. E2-treated cells also showed reduced intracellular labile iron content most evidently at 20 nM/48 h dose and reduced viability especially at 20 nM/72 h dose. E2-treated SKOV-3 showed slightly reduced intracellular labile iron content, reduced expression of hepcidin and significantly increased expression of TFR1 but not TFR2; FPN expression was overall similar to that of controls. The effects of E2 on intracellular iron metabolism in SKOV-3 were most evident at 5 nM/24 h dose. These findings suggest that E2 treatment induces intracellular iron efflux, which may minimize intracellular iron overload in cancer cells; disrupted expression of transferrin receptor 1 and/or 2 may help sustain a low intracellular iron environment.

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Section: Introductionmentioning

confidence: 99%

Estrogen-Dependent Downregulation of Hepcidin Synthesis Induces Intracellular Iron Efflux in Cancer Cells In Vitro

Shafarin¹,

Bajbouj²,

Serafy³

et al. 2016

Biol Med (Aligarh)

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“…The standard serum marker in routine use for the management of PC is carbohydrate antigen 19-9 (CA 19-9). However, its inadequate sensitivity and specificity limit its use for the early diagnosis of PC [3]. The European Group on Tumor Markers (EGTM) reported that CA 19-9 could not be recommended for screening purposes, but only for monitoring response to therapy in patients who have elevated levels [4].…”

Section: Introductionmentioning

confidence: 99%

Serum APN/CD13 as a novel diagnostic and prognostic biomarker of pancreatic cancer

et al. 2016

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Aminopeptidase N, also known as CD13, has been reported to be overexpressed in several cancers and may contribute to tumor metastasis and angiogenesis. The aim of this study was to evaluate whether serum APN/CD13 could be a potential biomarker for the diagnosis and prognosis of pancreatic cancer (PC). Serum APN/CD13 and carbohydrate antigen 19-9 (CA19-9) levels were measured from 382 participants, which comprised of 204 participants with PC, 48 participants with benign pancreatic tumors (BPT), 43 participants with chronic pancreatitis (CP) and 87 healthy controls (HC). We used receiver operating characteristic (ROC) analysis to calculate diagnostic accuracy. The association of serum APN/CD13 levels with the clinicopathological characteristics of PC patients and their survival was investigated. Serum APN/CD13 levels were substantially higher in PC patients than in controls. ROC analysis revealed that APN/CD13 was significantly better than CA19-9 in differentiating patients with PC from controls. Similar results were noted for early-stage PC. Moreover, the combined use of APN/CD13 and CA19-9 data improved the diagnostic accuracy for PC vs. controls, compared with either test alone. High serum APN/CD13 levels were associated with tumor size, lymph nodes, and metastasis (TNM) stage. Multivariate and ROC curve analyses revealed that high serum APN/CD13 level is an independent factor for predicting mortality and overall survival (OS). Moreover, Kaplan–Meier analysis demonstrated an inverse correlation between increased serum APN/CD13 level and OS. Our study established that serum APN/CD13 may be a novel diagnostic and prognostic biomarker for PC.

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“…In addition to its well-recognized relationship with inflammation and malnutrition, recent reports have shown serum ferritin to be closely connected with the presence and prognosis of malignancies such as renal cell carcinoma, neuroblastoma, pancreatic cancer, and hematologic malignancies [7,[25][26][27] . Moreover, oxidative tissue damage was found to increase tissue ferritin synthesis as well as its secretion [28] .…”

Section: Discussionmentioning

confidence: 99%

Serum Ferritin Predicts Mortality Regardless of Inflammatory and Nutritional Status in Patients Starting Dialysis: A Prospective Cohort Study

et al. 2015

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Background: The impact of serum ferritin on prognosis in patients starting hemodialysis (HD) is not fully elucidated. Methods: A prospective cohort of 946 incident HD patients from 26 dialysis centers in Korea was selected for this study. Patients were divided into tertiles according to natural logarithm (Ln) ferritin concentrations. Results: During a median follow-up of 39 months, 88 (9.3%) patients died. Multivariate Cox proportional hazard analysis demonstrated that Ln ferritin was independently associated with an increase in cardiovascular mortality risk (hazard ratio (HR) 1.604, 95% CI 1.040-2.474, p = 0.033), infection-related mortality risk (HR 1.916, 95% CI 1.056-3.476, p = 0.032), and all-cause mortality risk (HR 1.547, 95% CI 1.156-2.069, p = 0.003). Conclusion: Serum ferritin levels at the time of HD commencement were a significant independent risk factor for mortality regardless of systemic inflammation and nutritional status. Therefore, elevated serum ferritin levels could be an effective indicator for prognosis.

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Ferritin as an independent mortality predictor in patients with pancreas cancer. Results of a pilot study

Cited by 46 publications

References 16 publications

Estrogen-Dependent Downregulation of Hepcidin Synthesis Induces Intracellular Iron Efflux in Cancer Cells In Vitro

Estrogen-Dependent Downregulation of Hepcidin Synthesis Induces Intracellular Iron Efflux in Cancer Cells In Vitro

Serum APN/CD13 as a novel diagnostic and prognostic biomarker of pancreatic cancer

Serum Ferritin Predicts Mortality Regardless of Inflammatory and Nutritional Status in Patients Starting Dialysis: A Prospective Cohort Study

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