DOI QR코드

DOI QR Code

말기암환자에서 예후인자로서 혈청 Ferritin의 유용성

Prognostic Value of Serum Ferritin in Terminally Ill Cancer Patients

  • 이수희 (고려대학교 구로병원 가정의학과) ;
  • 최윤선 (고려대학교 구로병원 가정의학과) ;
  • 황인철 (가천대학교 길병원 가정의학과) ;
  • 염창환 (유셀클리닉) ;
  • 이준영 (고려대학교 의과대학 의학통계학교실)
  • 투고 : 2014.11.14
  • 심사 : 2015.01.26
  • 발행 : 2015.03.01

초록

목적: 말기암환자의 진료에 있어 여명을 예측하는 것은 매우 중요한 문제이다. 여러 악성 종양에서 혈청 ferritin이 증가되어 있고 높은 수치의 혈청 ferritin은 질병의 진행 및 나쁜 예후와 관련이 있다고 밝혀져 있으므로 본 연구에서는 말기암환자에서 ferritin과 생존기간과의 연관성을 알아보고 혈청 ferritin이 여명 예측 인자로 유용한지 검증하고자 하였다. 방법: 2012년 3월부터 2012년 6월까지 완화병동에 입원한 말기암환자 65명을 대상으로 혈청 ferritin을 포함한 기본적인 혈액검사를 시행하였고, 인구 통계학적 특성 및 임상증상 등을 조사하였다. 혈청 ferritin과 각 변수들간의 관련성을 파악하기 위해 Spearman's correlation analysis, Wilcoxon Rank Sum test 또는Kruskal-Wallis test등을 실시하였고 혈청 ferritin의 예후인자로서의 유용성을 평가하기 위해 다변수 콕스 비례위험 회귀분석(multivariable Cox's proportional hazard regression analysis)을 시행하였다. 결과: 상관 관계 분석 결과 ferritin은 생존기간과 유의한 음의 상관관계를 보였다. 단변량 분석에서 생존기간에 유의한 영향을 미치는 성별, ECOG 기능상태 지수, 크레아티닌, 백혈구 수치와 나이의 효과를 보정한 상태에서 혈청 ferritin은 말기암환자들의 생존기간과 통계적으로 유의한 관계를 나타내었다. 결론: 짧은 생존기간의 말기암환자에서도 혈청 ferritin은 독립적인 예후인자로 증명되었다. 기존의 여명 예측인자들과 더불어, 혈청 ferritin은 말기암환자들의 생존기간 예측에 도움을 줄 수 있을 것이라 생각한다.

Purpose: Predicting life expectancy of terminally ill cancer patients is very important. In many studies, ferritin is detected at higher levels in the sera of cancer patients, and higher ferritin level correlates with aggressiveness of disease and poor outcomes of patients. This study evaluated a prognostic role of serum ferritin levels in terminally ill cancer patients. Methods: This study enrolled 65 terminally ill cancer patients from March through June 2012. We assessed routine laboratory findings including serum ferritin levels as well as demographic and clinical characteristics of the patients. To examine the association between serum ferritin levels and patient's characteristics, we used Spearman's correlation analysis, Wilcoxon's rank sum test or Kruskal-Wallis test, as appropriately. For multivariate analysis, Cox's proportional hazard regression model was used to evaluate significance of serum ferritin levels as a prognostic factor. Results: A negative correlation between serum ferritin levels and survival time was found. After adjusting for sex, age, performance status, creatinine levels and white blood cell counts, serum ferritin levels were significantly associated with survival time. Conclusion: Even at the very end of life of terminal cancer patients, serum ferritin levels were an independent prognostic factor for survival.

키워드

참고문헌

  1. den Daas N. Estimating length of survival in end-stage cancer: a review of the literature. J Pain Symptom Manage 1995;10:548-55. https://doi.org/10.1016/0885-3924(95)00103-6
  2. Lee IC, Kim CK, Suh SY, Kim YS, Cho KH, Kang HC, et al. Validation of scoring system for survival prediction in terminal cancer patients in Korea. J Korean Acad Fam Med 2007;28:682-9.
  3. Christakis NA,Iwashyna TJ. Attitude and self-reported practice regarding prognostication in a national sample of internists. Arch Intern Med 1998;158:2389-95. https://doi.org/10.1001/archinte.158.21.2389
  4. Suh SY. Survival prediction of terminally ill cancer patients. Korean J Hosp Palliat Care 2007;10:171-7.
  5. Worwood M. Serum ferritin. CRC Crit Rev Clin Lab Sci 1979;10:171-204. https://doi.org/10.3109/10408367909147133
  6. Walters GO, Miller FM, Worwood M. Serum ferritin concentration and iron stores in normal subjects. J Clin Pathol 1973;26:770-2. https://doi.org/10.1136/jcp.26.10.770
  7. Cujic D, Stefanoska I, Golubović S. Serum ferritin in healthy women and breast cancer patients. JMB 2011;30:33-7.
  8. Narkhede HP, Muddeshwar MG, Mahajan VV. Breast cancer and serum ferritin-Menopausal status perspective: Menopause-A fickle determinant. Int J Res Med Sci 2014;2:258-63. https://doi.org/10.5455/2320-6012.ijrms20140249
  9. Mishra S, Sharma DC, Sharma P. Studies of biochemical parameters in breast cancer with and without metastasis. Indian J Clin Biochem 2004;19:71-5. https://doi.org/10.1007/BF02872394
  10. 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;137:733-44. https://doi.org/10.1007/s10549-012-2405-x
  11. Milman N, Pedersen LM. The serum ferritin concentration is a significant prognostic indicator of survival in primary lung cancer. Oncol Rep 2002;9:193-8.
  12. Kalousova M, Krechler T, Jachymova M, Kuběna AA, Zak A, Zima T. Ferritin as an independent mortality predictor in patients with pancreas cancer. Results of a pilot study. Tumour Biol 2012;33:1695-700. https://doi.org/10.1007/s13277-012-0426-z
  13. Ito H, Takagi Y, Ando Y, Kubo A, Hashimoto S, Tsutsui F, et al. Serum ferritin levels in patients with cervical cancer. Obstet Gynecol 1980;55:358-62. https://doi.org/10.1097/00006250-198003000-00018
  14. Tachibana T, Tanaka M, Takasaki H, Numata A, Maruta A, Ishigatsubo Y, et al. Pre-SCT serum ferritin is a prognostic factor in adult AML, but not ALL. Bone Marrow Transplant 2011;46:1268-9. https://doi.org/10.1038/bmt.2010.271
  15. Hann HW, Lange B, Stahlhut MW, McGlynn KA. Prognostic importance of serum transferrin and ferritin in childhood Hodgkin's disease. Cancer 1990;66:313-6. https://doi.org/10.1002/1097-0142(19900715)66:2<313::AID-CNCR2820660219>3.0.CO;2-J
  16. Roh ES, Lee JH, Hong YR, Park JS, Kim JS. Clinical utilities of serum ferritin as a marker of disease activity and prognostic factor in childhood tumors. Korean J Pediatr 2004;47:1319-24.
  17. Maxim PE, Veltri RW. Serum ferritin as a tumor marker in patients with squamous cell carcinoma of the head and neck. Cancer 1986;57:305-11. https://doi.org/10.1002/1097-0142(19860115)57:2<305::AID-CNCR2820570219>3.0.CO;2-D
  18. Jacobs A, Jones B, Ricketts C, Bulbrook RD, Wang DY. Serum ferritin concentration in early breast cancer. Br J Cancer 1976;34:286-90. https://doi.org/10.1038/bjc.1976.164
  19. Yeom CH, Choi YS, Ahn HY, Lee SH, Hwang IC. Oxidative stress level is not associated with survival in terminally ill cancer patients: a preliminary study. BMC Palliat Care 2014;13:14. https://doi.org/10.1186/1472-684X-13-14
  20. Alkhateeb AA, Connor JR. The significance of ferritin in cancer: anti-oxidation, inflammation and tumorigenesis. Biochim Biophys Acta 2013;1836:245-54.
  21. Rogers JT, Bridges KR, Durmowicz GP, Glass J, Auron PE, Munro HN. Translational control during the acute phase response. Ferritin synthesis in response to interleukin-1. J Biol Chem 1990;265:14572-8.
  22. Kew MC, Torrance JD, Derman D, Simon M, Macnab GM, Charlton RW, et al. Serum and tumour ferritins in primary liver cancer. Gut 1978;19:294-9. https://doi.org/10.1136/gut.19.4.294
  23. Hann HW, Levy HM, Evans AE. Serum ferritin as a guide to therapy in neuroblastoma. Cancer Res 1980;40:1411-3.
  24. 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:e51379. https://doi.org/10.1371/journal.pone.0051379
  25. Qi Y, Jamindar TM, Dawson G. Hypoxia alters iron homeostasis and induces ferritin synthesis in oligodendrocytes. J Neurochem 1995;64:2458-64.
  26. Tsuji Y, Ayaki H, Whitman SP, Morrow CS, Torti SV, Torti FM. Coordinate transcriptional and translational regulation of ferritin in response to oxidative stress. Mol Cell Biol 2000;20: 5818-27. https://doi.org/10.1128/MCB.20.16.5818-5827.2000
  27. Walker BL, Tiong JW, Jefferies WA. Iron metabolism in mammalian cells. Int Rev Cytol 2001;211:241-78. https://doi.org/10.1016/S0074-7696(01)11020-X
  28. Richardson DR, Ponka P. The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells. Biochim Biophys Acta 1997;1331:1-40. https://doi.org/10.1016/S0304-4157(96)00014-7
  29. Pirovano M, Maltoni M, Nanni O, Marinari M, Indelli M, Zaninetta G, et al. A new palliative prognostic score: a first step for the staging of terminally ill cancer patients. Italian Multicenter and Study Group on Palliative Care. J Pain Symptom Manage 1999;17:231-9. https://doi.org/10.1016/S0885-3924(98)00145-6
  30. McMillan DC, Elahi MM, Sattar N, Angerson WJ, Johnstone J, McArdle CS. Measurement of the systemic inflammatory response predicts cancer-specific and non-cancer survival in patients with cancer. Nutr Cancer 2001;41:64-9. https://doi.org/10.1080/01635581.2001.9680613
  31. Milman N, Mellemgaard A, Hansen S, Dombernowsky P. Bonemarrow hemosiderin iron and serum iron status markers in small-cell carcinoma of the lung. Int J Oncol 1993;3:29-32.
  32. Matzner Y, Konijn AM, Hershko C. Serum ferritin in hematologic malignancies. Am J Hematol 1980;9:13-22. https://doi.org/10.1002/ajh.2830090103
  33. Chanock S. Evolving risk factors for infectious complications of cancer therapy. Hematol Oncol Clin North Am 1993;7:771-93.