고형암 환자에서 종양 진행 예측인자로써 혈중 비타민 B12의 유용성
Prognostic Role of Serum Vitamin B12in Solid Tumor Patients
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연구배경: 혈중 비타민 B12는 종양 진단의 표지자이자 생존 예후인자로써의 가능성이 제기되었다. 본 연구에서는혈중 비타민 B12와 종양의 진행과의 관련성을 조사해보고자 한다. 방법: 비타민 B12 혈액검사와 영상검사를 반복하여 검사한고형암 환자를 대상으로 차트리뷰를 시행하였다. 총 55명의환자가 분석에 포함되었다. ROC 분석을 통해 비타민 B12 의 종양 예측과 관련된 cut-off value를 구하고자 하였으며, TTP에 대한 Kaplan-Meier method 및 Cox proportional hazard model 분석을 시행하였다. 간암 혹은 간전이로 인한 간의 병변 여부에 따른 소그룹분석을 시행하였다. 결과: 비타민 B12의 종양 증식 예측에 대한 cut-off value 는 691.4 pg/mL로 나타났으며, 민감도는 57.1%, 특이도는59.3%로 나타났다. 혈중 비타민 B12 농도가 691.4 pg/mL 이상인 환자는 그렇지 않은 환자군에 비해 짧은 TTP 기간을 보였다(2.1 months vs. 3.4 months, P=0.011). 소그룹분석에서, 간의 병변이 없는 환자군에서 비타민 B12가 691.4 pg/mL 이상인 환자는 그렇지 않은 환자군에 비해 짧은 TTP 기간을 보였으나(1.6 months vs. 6.3 months, P=0.021), 간의 병변을 가진 환자군에서는 유의미한 차이를 보이지 않았다. 높은 혈중 비타민 B12 수치(≥691.4 pg/mL)는 종양 진행에대한 독립적인 예측인자로 나타났다(adjusted HR 2.4, 95% CI 1.2-4.8, P=0.019). 결론: 혈중 비타민 B12는 특히 간의 병변이 없는 환자군에서 고형암의 종양 진행과 관련된 예측인자로 활용될 수있을 것으로 기대되었다. 추가적인 대규모의 전향적 연구가 진행되기를 기대한다.
Abstract
Background:Serum vitamin B12has been suggested as one of the cancer diagnostic markers and predictors for survival in cancer patients. In this study, we investigated the relationship between vitamin B12and tumor progression. Methods:Solid tumor patients who had serum vitamin B12levels and radiologic test follow-up were included in the study. A total of 55 patients were included. Receiver operating characteristic analysis was performed to determine the cut-off value of vitamin B12for tumor progression. Kaplan-Meier method and Cox proportional hazard model for time to progression (TTP) were performed. Subgroup analysis was performed on patients with or without liver lesion (hepatocellular carcinoma and liver metastasis). Results:The cut-off value of vitamin B12for tumor progression prediction was 691.4 pg/mL, the sensitivity was 57.1% and the specificity was 59.3%. Patients with vitamin B12≥691.4 pg/mL had shorter median TTP (2.1 months vs. 3.4 months, P=0.011). In subgroup analysis of patients without liver lesion, median TTP was significantly shorter in patients with vitamin B12≥691.4 pg/mL (1.6 months vs. 6.3 months, P=0.021), while there was no significant difference in TTP among the patients with liver lesion. Higher vitamin B12level (≥691.4 pg/mL) was an independent prognostic factor for tumor progression (adjusted hazard ratio 2.4, 95% confidence interval 1.2-4.8, P=0.019). Conclusions:Serum vitamin B12level can be used as a predictor of tumor progression in patients with solid tumors especially in patients without liver lesion. Additional large scale prospective studies are required to confirm this.
참고문헌 (30)
- Oh R, "Vitamin B12 deficiency", Am Fam Physician, 67(5), pp.979~986 (2003)
- Lechner K, "Vitamin B12 deficiency. New data on an old them", Wien Klin Wochenschr, 117(17), pp.579~591 (2005)
- Arendt JF, "Cobalamin related parameters and disease patterns in patients with increased serum cobalamin levels", PLoS One, 7(9), pp.e45979~ (2012)
- Arendt JF, "Unexpected high plasma cobalamin: proposal for a diagnostic strategy", Clin Chem Lab Med, 51(3), pp.489~496 (2013)
- Arendt JF, "Elevated plasma vitamin B12 levels as a marker for cancer: a population-based cohort study", J Natl Cancer Inst, 105(23), pp.1799~1805 (2013)
- Arendt JF, "Elevated plasma vitamin B12 levels and cancer prognosis: a population-based cohort study", Cancer Epidemiology, 40, pp.158~165 (2016)
- Lin CY, "Elevated serum vitamin B(12) levels in association with tumor markers as the prognostic factors predictive for poor survival in patients with hepatocellular carcinoma", Nutr Cancer, 62(2), pp.190~197 (2010)
- Kelly L, "The B12", CRP index as a simple prognostic indicator in patients with advanced cancer: a confirmatory study, 2007, pp.18(8), 1395~1399
- Eisenhauer EA, "New response evaluation criteria in solid tumours:revised RECIST guideline (version 1.1)", Eur J Cancer, 45(2), pp.228~247 (2009)
- Tavares F., "Is the B12", CRP index more accurate than you at predicting life expectancy in advanced cancer patients?, 2010, pp.40(1), e12~e13
- Ryg J, "Cancer incidence in persons with elevated cobalamin levels", Eur J Clin Invest, 43(6), pp.557~561 (2013)
- Schwettmann L, "Reference interval and status for serum folate and serum vitamin B12 in a Norwegian population", Clin Lab, 61(8), pp.1095~1100 (2015)
- Bor MV, "A daily intake of approximately 6 microg vitamin B-12 appears to saturate all the vitamin B-12-related variables in Danish postmenopausal women", Am J Clin Nutr, 83(1), pp.52~58 (2006)
- Salles N, "High vitamin B12 level: a strong predictor of mortality in elderly inpatients", J Am Geriatr Soc, 53(5), pp.917~918 (2005)
- Duffy MJ., "Tumor markers in clinical practice: a review focusing on common solid cancers", Med Princ Pract, 22(1), pp.4~11 (2013)
- Wu AH, "Markers for hepatocellular carcinoma", Immunol Ser, 53, pp.403~422 (1990)
- Zhang K, "Perspectives on a combined test of multi serum biomarkers in China: towards screening for and diagnosing hepatocellular carcinoma at an earlier stage", Drug Discov Ther, 8(3), pp.102~109 (2014)
- Daniele B, "Alpha-fetoprotein and ultrasonography screening for hepatocellular carcinoma", Gastroenterology, 127(5 suppl 1), pp.S108~S112 (2004)
- Farinati F, "Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither?", Am J Gastroenterol, 101(3), pp.524~532 (2006)
- Yu J, "Differences and correlation of serum CEA, CA19-9 and CA72-4 in gastric cancer", Mol Clin Oncol, 4(3), pp.441~449 (2016)
- Du R, "Association between serum CA 19-9 and metabolic syndrome: a cross-sectional study", J Diabetes, 9(11), pp.1040~1047 (2017)
- Virgilio E, "Measuring intragastric tumor markers in gastric cancer patients: a systematic literature review on significance and reliability", Anticancer Res, 37(6), pp.2817~2821 (2017)
- Solomon LR., "Disorders of cobalamin (vitamin B12) metabolism:emerging concepts in pathophysiology, diagnosis and treatment", Blood Rev, 21(3), pp.113~130 (2007)
- Collin SM, "Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis", Cancer Epidemiol Biomarkers Prev, 19(6), pp.1632~1642 (2010)
- Lildballe DL, "Haptocorrin as marker of disease progression in fibrolamellar hepatocellular carcinoma", Eur J Surg Oncol, 37(1), pp.72~79 (2011)
- Sysel AM, "Immunohistochemical quantification of the vitamin B12 transport protein (TCII), cell surface receptor (TCII-R) and Ki-67 in human tumor xenografts", Anticancer Res, 33(10), pp.4203~4212 (2013)
- Donkena KV, "Vitamin Bs, one carbon metabolism and prostate cancer", Mini Rev Med Chem, 10(14), pp.1385~1392 (2010)
- Ermens AA, "Significance of elevated cobalamin (vitamin B12) levels in blood", Clin Biochem, 36(8), pp.585~590 (2003)
- Fenech MF, "Folate, vitamin B12, homocysteine status and chromosome damage rate in lymphocytes of older men", Carcinogenesis, 18(7), pp.1329~1336 (1997)
- Kapiszewska M, "Uracil misincorporation into DNA of leukocytes of young women with positive folate balance depends on plasma vitamin B12concentrations and methylenetetrahydrofolate reductase polymorphisms. A pilot study", J Nutr Biochem, 16(8), pp.467~478 (2005)