Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2018

Open Access 01-12-2018 | Research article

Significance of serum ferritin as a prognostic factor in advanced hepatobiliary cancer patients treated with Korean medicine: a retrospective cohort study

Authors: Anna Song, Wankyu Eo, Sehyun Kim, Bumsang Shim, Sookyung Lee

Published in: BMC Complementary Medicine and Therapies | Issue 1/2018

Login to get access

Abstract

Background

Advanced hepatobiliary cancers are highly lethal cancers that require precise prediction in clinical practice. Serum ferritin level increases in malignancy and high serum ferritin level is associated with poor survival in various cancers. This study aimed to identify whether serum ferritin could independently predict the overall survival (OS) of patients with advanced hepatobiliary cancers.

Methods

The retrospective cohort study was performed by reviewing medical records of patients with advanced hepatobiliary cancers from June 2006 to September 2016. The demographic and clinicopathological characteristics as well as the biochemical markers were evaluated at the initiation of Korean medicine (KM) treatment. The OS was calculated using Kaplan-Meier estimates. The Cox proportional hazard model was used to identify the independent prognostic significance of serum ferritin for survival.

Results

The median OS of all subjects was 5.1 months (range, 0.5–114.9 months). The median OS of group with low ferritin levels and that with high ferritin levels was 7.5 months (range, 0.7–114.9 months) and 2.8 months (range, 0.5–22.8 months), respectively (P < 0.001). The results of the univariate analysis showed that the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) (P = 0.002), tumor type (P = 0.001), prior treatment (P = 0.023), serum ferritin (P < 0.001), hemoglobin (P = 0.002), total bilirubin (P = 0.002), gamma-glutamyl transpeptidase (P = 0.007), albumin (P = 0.013), white blood cell (P = 0.002), and C-reactive protein (CRP) (P < 0.001) were significant factors for the patients’ survival outcome. On multivariate analysis controlling confounding factors, ferritin (P = 0.041), CRP (P = 0.010), ECOG-PS (P = 0.010), and tumor type (P = 0.018) were identified as independent prognostic factors for survival.

Conclusions

These results indicate that serum ferritin is a valid clinical biochemical marker to predict survival of patients with advanced hepatobiliary cancers.
Literature
1.
Jung KW, Won YJ, Oh CM, Kong HJ, Lee DH, Lee KH. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2014. Cancer Res Treat. 2017;49(2):292–305.CrossRefPubMedPubMedCentral
2.
Woo SM, Yoon KA, Hong EK, Park WS, Han SS, Park SJ, et al. DCK expression, a potential predictive biomarker in the adjuvant gemcitabine chemotherapy for biliary tract cancer after surgical resection: results from a phase II study. Oncotarget. 2017;8(46):81394–404.CrossRefPubMedPubMedCentral
3.
Tabrizian P, Jibara G, Hechtman JF, Franssen B, Labow DM, Schwartz ME, et al. Outcomes following resection of intrahepatic cholangiocarcinoma. HPB (Oxford). 2015;17(4):344–51.CrossRef
4.
Hyder O, Hatzaras I, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H, et al. Recurrence after operative management of intrahepatic cholangiocarcinoma. Surgery. 2013;153(6):811–8.CrossRefPubMedPubMedCentral
5.
Jarnagin WR, Ruo L, Little SA, Klimstra D, D'Angelica M, DeMatteo RP, et al. Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies. Cancer. 2003;98(8):1689–700.CrossRefPubMed
6.
Augustine MM, Fong Y. Epidemiology and risk factors of biliary tract and primary liver tumors. Surg Oncol Clin N Am. 2014;23(2):171–88.CrossRefPubMed
7.
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.CrossRefPubMed
8.
Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25–34.CrossRefPubMed
9.
Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–81.CrossRefPubMed
10.
Park HS, Park JS, Chun YJ, Roh YH, Moon J, Chon HJ, et al. Prognostic factors and scoring model for survival in metastatic biliary tract Cancer. Cancer Res Treat. 2017;49(4):1127–39.CrossRefPubMedPubMedCentral
11.
Bridgewater J, Lopes A, Wasan H, Malka D, Jensen L, Okusaka T, et al. Prognostic factors for progression-free and overall survival in advanced biliary tract cancer. Ann Oncol. 2016;27(1):134–40.CrossRefPubMed
12.
13.
Zacharski LR, Ornstein DL, Woloshin S, Schwartz LM. Association of age, sex, and race with body iron stores in adults: analysis of NHANES III data. Am Heart J. 2000;140(1):98–104.CrossRefPubMed
14.
Tran TN, Eubanks SK, Schaffer KJ, Zhou CY, Linder MC. Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron. Blood. 1997;90(12):4979–86.PubMed
15.
Kowdley KV, Belt P, Wilson LA, Yeh MM, Neuschwander-Tetri BA, Chalasani N, et al. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. Hepatology. 2012;55(1):77–85.CrossRefPubMed
16.
Facciorusso A, Del Prete V, Antonino M, Neve V, Crucinio N, Di Leo A, et al. Serum ferritin as a new prognostic factor in hepatocellular carcinoma patients treated with radiofrequency ablation. J Gastroenterol Hepatol. 2014;29(11):1905–10.CrossRefPubMed
17.
Ji M, Li XD, Shi HB, Ning ZH, Zhao WQ, Wang Q, et al. Clinical significance of serum ferritin in elderly patients with primary lung carcinoma. Tumour Biol. 2014;35(10):10195–9.CrossRefPubMed
18.
Kalousova M, Krechler T, Jachymova M, Kubena AA, Zak A, Zima T. Ferritin as an independent mortality predictor in patients with pancreas cancer. Results of a pilot study. Tumour Biol. 2012;33(5):1695–700.CrossRefPubMed
19.
Koyama S, Fujisawa S, Watanabe R, Itabashi M, Ishibashi D, Ishii Y, et al. Serum ferritin level is a prognostic marker in patients with peripheral T-cell lymphoma. Int J Lab Hematol. 2017;39(1):112–7.CrossRefPubMed
20.
Lee S, Song A, Eo W. Serum ferritin as a prognostic biomarker for survival in relapsed or refractory metastatic colorectal Cancer. J Cancer. 2016;7(8):957–64.CrossRefPubMedPubMedCentral
21.
Song A, Eo W, Lee S. Comparison of selected inflammation-based prognostic markers in relapsed or refractory metastatic colorectal cancer patients. World J Gastroenterol. 2015;21(43):12410–20.CrossRefPubMedPubMedCentral
22.
Bertuzzo VR, Cescon M, Ravaioli M, Grazi GL, Ercolani G, Del Gaudio M, et al. Analysis of factors affecting recurrence of hepatocellular carcinoma after liver transplantation with a special focus on inflammation markers. Transplantation. 2011;91(11):1279–85.CrossRefPubMed
23.
24.
Park JH, Moon G. Effect of allergen removed Rhus Verniciflua extract on inhibition of tumor metastasis. J of Kor Traditional Oncology. 2010;15(1):47–61.
25.
Son YO, Lee KY, Lee JC, Jang HS, Kim JG, Jeon YM, et al. Selective antiproliferative and apoptotic effects of flavonoids purified from Rhus verniciflua Stokes on normal versus transformed hepatic cell lines. Toxicol Lett. 2005;155(1):115–25.CrossRefPubMed
26.
Yoon SW, Park SJ, Kim KS, Jung HS, Choi WC. The study on the process and quality control of Rhus Verniciflua stokes extract (Nexia). J of Kor Traditional Oncology. 2006;11(1):9.
27.
WHO, UNICEF. UNU: Iron deficiency anaemia: assessment, prevention, and control. A guide for programme managers.. In: Geneva, World Health Organization; 2001.
28.
29.
Lee SH, Song IH, Noh R, Kang HY, Kim SB, Ko SY, et al. Clinical outcomes of patients with advanced hepatocellular carcinoma treated with sorafenib: a retrospective study of routine clinical practice in multi-institutions. BMC Cancer. 2015;15:236.CrossRefPubMedPubMedCentral
30.
Park K, Kim KP, Park S, Chang HM. Comparison of gemcitabine plus cisplatin versus capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer. Asia Pac J Clin Oncol. 2017;13(1):13–20.CrossRefPubMed
31.
Jang HS, Kook SH, Son YO, Kim JG, Jeon YM, Jang YS, et al. Flavonoids purified from Rhus verniciflua Stokes actively inhibit cell growth and induce apoptosis in human osteosarcoma cells. Biochim Biophys Acta. 2005;1726(3):309–16.CrossRefPubMed
32.
Lee JC, Lee KY, Kim J, Na CS, Jung NC, Chung GH, et al. Extract from Rhus verniciflua Stokes is capable of inhibiting the growth of human lymphoma cells. Food Chem Toxicol. 2004;42(9):1383–8.CrossRefPubMed
33.
Kim MJ, Choi WC, Barshinikov AM, Kobayashi A. Anticancer and antioxidant activity of allergen-removed extract in Rhus verniciflua Stokes. Korean Journal of Medicinal Crop Science. 2002;10(4):288–93.
34.
Lee SK, Jung HS, Eo WK, Lee SY, Kim SH, Shim BS. Rhus verniciflua Stokes extract as a potential option for treatment of metastatic renal cell carcinoma: report of two cases. Ann Oncol. 2010;21(6):1383–5.CrossRefPubMed
35.
Lee J, Chae J, Lee S, Kim K, Eo W, Kim S, et al. The efficacy and safety of standardized allergen-removed Rhus verniciflua extract as maintenance therapy after first-line chemotherapy in patients with advanced non-small cell lung Cancer. The American Journal of Chinese Medicine. 2013;41(04):773–87.CrossRefPubMed
36.
Lee S, Kim K, Jung H, Cheon S, Kim S, Eo W, et al. Efficacy and safety of standardized allergen-removed Rhus verniciflua Stokes extract in patients with advanced or metastatic pancreatic cancer: a Korean single-center experience. Oncology. 2011;81(5–6):312–8.CrossRefPubMed
37.
Kim KS, Jung HS, Choi WC, Eo WK, Cheon SH. A case of recurred hepatocellular carcinoma refractory to doxorubicin after liver transplantation showing response to herbal medicine product, Rhus verniciflua Stokes extract. Integr Cancer Ther. 2010;9(1):100–4.CrossRefPubMed
38.
Nimeiri HS, Singh DA, Kasza K, Taber DA, Ansari RH, Vokes EE, et al. The epothilone B analogue ixabepilone in patients with advanced hepatobiliary cancers: a trial of the University of Chicago phase II consortium. Investig New Drugs. 2010;28(6):854–8.CrossRef
39.
40.
Hauser CA, Stockler MR, Tattersall MH. Prognostic factors in patients with recently diagnosed incurable cancer: a systematic review. Support Care Cancer. 2006;14(10):999–1011.CrossRefPubMed
41.
Chiorean EG, Ramasubbaiah R, Yu M, Picus J, Bufill JA, Tong Y, et al. Phase II trial of erlotinib and docetaxel in advanced and refractory hepatocellular and biliary cancers: Hoosier oncology group GI06-101. Oncologist. 2012;17(1):13.CrossRefPubMedPubMedCentral
42.
Yoon YI, Hwang S, Lee YJ, Kim KH, Ahn CS, Moon DB, et al. Postresection outcomes of combined hepatocellular carcinoma-cholangiocarcinoma, hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Gastrointest Surg. 2016;20(2):411–20.CrossRefPubMed
43.
Shiba H, Furukawa K, Fujiwara Y, Futagawa Y, Haruki K, Wakiyama S, et al. Postoperative peak serum C-reactive protein predicts outcome of hepatic resection for hepatocellular carcinoma. Anticancer Res. 2013;33(2):705–9.PubMed
44.
Schweitzer N, Fischer M, Kirstein MM, Berhane S, Kottas M, Sinn M, et al. Risk estimation for biliary tract cancer: development and validation of a prognostic score. Liver Int. 2017;
45.
Boyd D, Vecoli C, Belcher DM, Jain SK, Drysdale JW. Structural and functional relationships of human ferritin H and L chains deduced from cDNA clones. J Biol Chem. 1985;260(21):11755–61.PubMed
46.
Orino K, Harada S, Natsuhori M, Takehara K, Watanabe K. Kinetic analysis of bovine spleen apoferritin and recombinant H and L chain homopolymers: iron uptake suggests early stage H chain ferroxidase activity and second stage L chain cooperation. Biometals. 2004;17(2):129–34.CrossRefPubMed
47.
Jones BM, Worwood M, Jacobs A. Serum ferritin in patients with cancer: determination with antibodies to HeLa cell and spleen ferritin. Clin Chim Acta. 1980;106(2):203–14.CrossRefPubMed
48.
Arosio P, Yokota M, Drysdale JW. Structural and immunological relationships of isoferritins in normal and malignant cells. Cancer Res. 1976;36(5):1735–9.PubMed
49.
Hann HW, Lange B, Stahlhut MW, McGlynn KA. Prognostic importance of serum transferrin and ferritin in childhood Hodgkin's disease. Cancer. 1990;66(2):313–6.CrossRefPubMed
50.
Alkhateeb AA, Leitzel K, Ali SM, Campbell-Baird C, Evans M, Fuchs EM, et al. Elevation in inflammatory serum biomarkers predicts response to trastuzumab-containing therapy. PLoS One. 2012;7(12):e51379.CrossRefPubMedPubMedCentral
51.
Alkhateeb AA, Han B, Connor JR. Ferritin stimulates breast cancer cells through an iron-independent mechanism and is localized within tumor-associated macrophages. Breast Cancer Res Treat. 2013;137(3):733–44.CrossRefPubMed
52.
53.
Kell DB, Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics. 2014;6(4):748–73.CrossRefPubMed
54.
Nielsen P, Gunther U, Durken M, Fischer R, Dullmann J. Serum ferritin iron in iron overload and liver damage: correlation to body iron stores and diagnostic relevance. J Lab Clin Med. 2000;135(5):413–8.CrossRefPubMed
55.
Chapman RW, Gorman A, Laulicht M, Hussain MA, Sherlock S, Hoffbrand AV. Binding of serum ferritin to concanavalin a in patients with iron overload and with chronic liver disease. J Clin Pathol. 1982;35(5):481–6.CrossRefPubMedPubMedCentral
Metadata
Title
Significance of serum ferritin as a prognostic factor in advanced hepatobiliary cancer patients treated with Korean medicine: a retrospective cohort study
Authors
Anna Song
Wankyu Eo
Sehyun Kim
Bumsang Shim
Sookyung Lee
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2018
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-018-2240-7

Other articles of this Issue 1/2018

BMC Complementary Medicine and Therapies 1/2018 Go to the issue

Research article

Enhancement of neuroprotective activity of Sagunja-tang by fermentation with lactobacillus strains

Research article

Glycyrrhiza glabra HPLC fractions: identification of Aldehydo Isoophiopogonone and Liquirtigenin having activity against multidrug resistant bacteria

Research article

Genotoxicity study of Ethiopian medicinal plant extracts on HepG2 cells

Research article

Spinacia oleracea extract attenuates disease progression and sub-chondral bone changes in monosodium iodoacetate-induced osteoarthritis in rats

Research article

The mutagenic and antimutagenic activity of Sutherlandia frutescens extracts and marker compounds

Research article

Identifying strengths and weaknesses of the integration of biomedical and herbal medicine units in Ghana using the WHO Health Systems Framework: a qualitative study