1.Value of procalcitonin in the diagnosis of perioperative infection in patients undergoing primary hip replacement.
Shan-Zheng ZHANG ; Zhi-Jun LUO ; Ling YE
China Journal of Orthopaedics and Traumatology 2022;35(11):1065-1069
OBJECTIVE:
To analyze the value of procalcitonin (PCT) in the diagnosis of perioperative infection associated with implants in patients with primary hip arthroplasty.
METHODS:
A retrospective study was conducted on 150 patients who underwent primary hip arthroplasty from June 2018 to June 2020, including 86 males and 64 females, aged from 47 to 77 years old with an average of (57.04±7.43) years. All patients with primary hip arthroplasty were divided into infection group and non infection group according to whether there was infection after operation. Blood samples were collected from the elbow vein before operation (D0) and on the 4, 6, 8 days after operation(D4, D6 and D8) respectively to detect the serum PCT level and white blood cell count (WBC) level.
RESULTS:
Among 150 patients with primary hip arthroplasty, 34 patients with postoperative infection were in the infection group, and 116 patients without postoperative infection were in the noninfection group. In the infection group, there were 19 cases of superficial surgical site infection(55.88%, 19/34), 9 cases of urinary tract infection (26.47%, 9/34), and 6 cases of pneumonia(17.65%, 6/34). After bacterial culture in the infection group, there were 9 cases of Staphylococcus aureus, 3 cases of Escherichia coli, 3 cases of Staphylococcus epidermidis, 3 cases of Streptococcus constellation, 3 cases of Candida albicans, 6 cases of Klebsiella pneumoniae, 2 cases of Escherichia coli and Streptococcus agalactis, 3 cases of coagulase invisible staphylococcus and Burkholderia cepacia, 2 cases of Escherichia coli, Enterococcus faecalis and Pseudomonas aeruginosa. There was no significant difference in PCT levels between two groups in D0(P=0.081), D4(P=0.069) and D6(P=0.093), but there was significant difference in D8(P=0.007). There was no significant difference in WBC between two groups at any time point(P>0.05). The results of receiver operating characteristic curve(ROC) showed that the AUC of PCT diagnosis was 0.978[95%CI(0.933, 1.022)] and that of WBC was 0.562[95%CI(0.398, 0.726)], PCT was an important predictor of infection after primary hip arthroplasty(AUC>0.9). When the critical value was 0.526 ng/ml, the sensitivity and specificity of PCT diagnosis are 36% and 100%, respectively, WBC was not a significant predictor of infection after primary hip arthroplasty (0.5
Male
;
Female
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Humans
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Middle Aged
;
Aged
;
Procalcitonin
;
Calcitonin
;
Arthroplasty, Replacement, Hip/adverse effects*
;
Protein Precursors
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Retrospective Studies
;
C-Reactive Protein/analysis*
;
Calcitonin Gene-Related Peptide
;
Escherichia coli
2.Prognostic significance of plasma gelsolin in severe burn patients with sepsis.
Lifeng HUANG ; Yongming YAO ; Ning DONG ; Lixin HE ; Qinghong ZHANG ; Yan YU ; Zhiyong SHENG
Chinese Journal of Burns 2016;32(2):77-81
OBJECTIVETo investigate the changes in plasma gelsolin (pGSN) levels in severe burn patients with sepsis, and to evaluate the prognosis of patients when combined with other related clinical indexes.
METHODSSixty-five severe burn patients with sepsis hospitalized from June 2013 to June 2015 conforming to the study criteria were divided into death group (n=24) and survival group (n=41) according to the clinical outcome on post sepsis diagnosis day (PSD) 28. The pGSN levels of patients were determined on PSD 1, 3, 7, and 14 with double antibody sandwich enzyme-linked immunosorbent assay. The serum level of C-reactive protein (CRP), serum level of procalcitonin, lactate level of arterial blood, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score were determined or recorded on PSD 1. Data were processed with repeated measurement analysis of variance, t test, and chi-square test. On PSD 1, the pGSN level, serum level of CRP, serum level of procalcitonin, lactate level of arterial blood, APACHE II score, and SOFA score of 65 patients were collected to screen the independent risk factors related to death with single factor and multi-factor Logistic regression analysis. Receiver operating characteristic (ROC) curves of the independent risk factors related to death were plotted to evaluate the predictive power for death in 65 patients.
RESULTS(1) The pGSN levels of patients in death group on PSD 1, 3, 7, and 14 were respectively (146±44), (85±24), (28±7), and (19±4) mg/L, obviously lower than those in survival group [(287±82), (179±51), (196±56), and (249±67) mg/L, with t values from 1.735 to 4.304, P<0.05 or P<0.01]. (2) The serum level of CRP, serum level of procalcitonin, lactate level of arterial blood, APACHE II score, and SOFA score of patients in death group on PSD 1 were respectively (56±7) mg/L, (12.54±0.82) μg/L, (2.74±0.27) mmol/L, (24.3±2.4) points, and (11.43±0.57) points, significantly higher than those in survival group [(35±4) mg/L, (2.38±0.16) μg/L, (1.83±0.12) mmol/L, (15.0±1.5) points, and (7.22±0.23) points, with t values from 1.902 to 3.883, P<0.05 or P<0.01]. (3) Multi-factor Logistic regression analysis showed that the pGSN level (odds ratio: 6.83, 95% confidence interval: 4.33-10.25, P<0.01) and APACHE II score (odds ratio: 5.27, 95% confidence interval: 2.28-9.16, P<0.01) were the independent risk factors related to death in 65 patients on PSD 1. (4) The total areas under the ROC curves of pGSN level and APACHE II score for predicting death of 65 patients on PSD 1 were respectively 0.89 and 0.86, and 142 mg/L and 21 points were respectively chosen as the optimal threshold values, with sensitivity of 87% and 83% and specificity of 86% and 89%.
CONCLUSIONSFor severe burn patients with sepsis, lowering of pGSN level and elevation of APACHE II score are obviously correlated with increase in case fatality rates. Monitoring the dynamic changes in pGSN level and APACHE II score during the early stage may be useful to predict the prognosis of severe burn patients with sepsis.
Burns ; complications ; C-Reactive Protein ; analysis ; Calcitonin ; blood ; Calcitonin Gene-Related Peptide ; Enzyme-Linked Immunosorbent Assay ; Gelsolin ; blood ; Hospitalization ; Humans ; Organ Dysfunction Scores ; Prognosis ; Protein Precursors ; blood ; ROC Curve ; Regression Analysis ; Risk Factors ; Sepsis ; blood ; diagnosis ; Severity of Illness Index
3.Bone marrow metastasis presenting as bicytopenia originating from hepatocellular carcinoma.
Young Mi HONG ; Ki Tae YOON ; Mong CHO ; Dae Hwan KANG ; Hyung Wook KIM ; Cheol Woong CHOI ; Su Bum PARK ; Jeong HEO ; Hyun Young WOO ; Won LIM ; S M BAKHTIAR UI ISLAM
Clinical and Molecular Hepatology 2016;22(2):267-271
The bone is a common site for metastasis in hepatocellular carcinoma (HCC). However, bone marrow metastasis from HCC is rarely reported, and its frequency is unclear. Here we report a rare case of bone marrow metastasis that presented as bicytopenia originating from HCC without bone metastasis. A 58-year-old man was admitted for investigation of a liver mass with extensive lymph node enlargement that was detected when examining his general weakness and weight loss. Laboratory findings revealed anemia, thrombocytopenia, mild elevated liver enzymes, normal prothrombin time percentage and high levels of tumor markers (α-fetoprotein and des-γ-carboxyprothrombin). Abdominal computed tomography showed multiple enhanced masses in the liver and multiple enlarged lymph nodes in the abdomen. A bone marrow biopsy revealed only a few normal hematopoietic cells and abundant tumor cells. Despite its rarity, bone marrow metastasis should always be suspected in HCC patients even if accompanied by cirrhosis.
Biomarkers/analysis
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Bone Marrow/*pathology
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Carcinoma, Hepatocellular/*diagnosis
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Humans
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Liver Neoplasms/*diagnosis
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Male
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Middle Aged
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Neoplasm Metastasis
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Positron Emission Tomography Computed Tomography
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Protein Precursors/analysis
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Prothrombin/analysis
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Thrombocytopenia/diagnosis
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Tomography, X-Ray Computed
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alpha-Fetoproteins/analysis
4.Early identification of refractory Mycoplasma pneumoniae pneumonia in children.
Zhen WANG ; Ya-Chun LI ; Lu CHEN
Chinese Journal of Contemporary Pediatrics 2015;17(11):1189-1192
OBJECTIVETo investigate the clinical indicators for early identification of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children.
METHODSThe clinical data of 142 children with Mycoplasma pneumoniae pneumonia (MPP) between January 2014 and June 2015 were retrospectively studied. Among the 142 children, there were 32 cases of RMPP and 110 cases of non-refractory MPP. The clinical data were compared between the RMPP and non-refractory MPP groups.
RESULTSThe percentage of school-age children in the RMPP group was higher than in the non-refractory MPP group (P<0.05). The mean onset age in the RMPP group was older than the non-refractory MPP group (P<0.05). Steroid was used in 93.8% of RMPP children compared with 7.3% of non-refractory MPP children (P<0.001). Consolidation of lung on chest X-Ray was shown in 87.5% of RMPP children compared with 42.7% of non-refractory MPP children (P<0.001). The incidence of pleural effusion in the RMPP group was higher than in the non-refractory MPP group (P<0.001). The RMPP group had higher percentages of individuals with CRP>40 mg/L and ESR>30 mm/h+LDH>300 IU/L than the non-refractory MPP group (P<0.05).
CONCLUSIONSRMPP is common in school-age children. Consolidation of lung on chest X-Ray, pleural effusion and increased levels of CRP and ESR+LDH may be helpful to early identification of RMPP in children.
C-Reactive Protein ; analysis ; Calcitonin ; blood ; Child ; Child, Preschool ; Female ; Humans ; L-Lactate Dehydrogenase ; blood ; Male ; Pneumonia, Mycoplasma ; blood ; diagnosis ; Protein Precursors ; blood ; Retrospective Studies
5.Clinical study of Pentraxin 3 in diagnosing the severity and cardiovascular function of the children with sepsis.
Xiayan KANG ; Yimin ZHU ; Xinping ZHANG
Chinese Journal of Pediatrics 2015;53(8):592-598
OBJECTIVETo study the value of Pentraxin 3 (PTX3) in diagnosing the severity and cardiovascular function of the critically ill children. Method A total of 178 patients who were older than 28 days, with acute infection of respiratory or neurological system, excluding chronic or special disease, and admitted to the pediatric intensive care unit (PICU) of Hunan Children's Hospital from October 1, 2013 to April 30, 2014 were enrolled, including 102 male cases and 76 female cases. The ages ranged from 1 month to 13 years and 1 month, 78 of them were less than 1 year old ; 58 cases were between 1 to 3 years old; 42 cases were above 3 years old; 101 cases were diagnosed as respiratory system diseases, 77 cases had nervous system diseases. PTX3 was detected with enzyme-linked immunosorbent assay (ELISA) within 1 d after enrollment, at 3 days and 7 days, meanwhile, troponin, myocardial enzyme, brain-type natriuretic peptide (BNP), C-reactive protein (CRP), plasma calcitonin (PCT) and WBC etc. Were measured. According to the plasma PTX3 value which were measured within 24 h after enrollment the patients were divided into three groups: mildly elevated group (< 44 µg/L) 41 cases; moderately elevated group (44 - < 132 µg/L) in 66 cases; severely elevated group 71 cases (132 µg/L or higher). Those 178 patients were divided into 3 groups according to the degree of infection: non-sepsis group (78 cases), sepsis group (70 cases), severe sepsis group (30 cases), and in each group, those with heart failure were respectively 19 cases, 28 cases, 17 cases. Analysis of the plasma PTX3 expression changes in different clinical manifestations, different condition, different degrees of organ damages and prognosis for the patient. The continuous variables were analyzed with t-test, F-test, H-test, the categorical variables were analyzed with Chi-square test, and the correlation analysis was performed to calculate Pearson coefficients.
RESULTThe PTX3 value measured within 24 h after enrollment increased with the degree of infection (50. 4(35. 2,70. 4) µg/L; 175. 8 (99. 6, 309. 9) µg/L;419. 9 (168. 3, 468. 6) µg/L; H = 88. 345, P = 0. 000). PTX3 level gradually declined, while in severe sepsis group decreased slowly (P <0. 05); the area under the ROC curve of Plasma PTX3 was larger than that of other inflammatory markers such as CRP and PCT, white blood cells and neutrophils in the diagnosis of sepsis; while the former three are PTX3, PCT and CRP (the sensitivity and specificity respectively were 0. 77, 0. 68; 0. 66, 0. 6; 0. 47, 0. 55); the PTX3 value of the severely elevated group was significantly higher than those of the mildly and moderately elevated groups (P <0. 05). The proportion of having 3 or more organs failure increased as the PTX3 rising among the groups of mildly elevated group, moderately elevated group and severely elevated group (1(2. 4%), 4(6. 1%), 14(19. 7%) χ2 =16. 16,P = 0. 000); and in each group, the proportion of having good and poor prognosis for these three groups were different (33 (80.5%) and 8 (19. 5%), 35 (53%) and 31 (47%), 28 (39.4%) and 43 (60.6%), χ = 17. 663, P = 0. 000). The K-M curve for these three groups had statistically significant difference (χ2 = 7. 086, P = 0. 029). Those with heart failure had higher PTX3 value than those in non-heart failure at the same degree of infection. PTX3 value increased with myocardial enzyme (troponin, creatine kinase isoenzyme, BNP) levels. In the diagnosis of heart failure, the area under the ROC curve were respectively PTX3 0. 824; BNP 0. 772; CM-KB 0. 643; CNTIO. 671, the sensitivity and specificity were PTX3 0. 8, 0. 58; CK-MB 0. 56,0. 79; CTNI 0. 60,0. 69; BNP 0. 73, 0. 58. In terms of predicting the prognosis of sepsis with heart failure complications, the PTX3 value's area under ROC curve was larger than that of BNP (respectively 0. 844, 0. 472).
CONCLUSIONThe PTX3 is an objective biochemical marker in diagnosis of sepsis; it is helpful in assessment of severity and prognosis of sepsis; it also has a certain clinical value in the assessment of sepsis cardiovascular function damage.
Adolescent ; Biomarkers ; blood ; C-Reactive Protein ; analysis ; Calcitonin ; blood ; Cardiovascular System ; physiopathology ; Child ; Child, Preschool ; Creatine Kinase ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant ; Intensive Care Units, Pediatric ; Leukocyte Count ; Male ; Natriuretic Peptide, Brain ; blood ; Prognosis ; Protein Precursors ; blood ; ROC Curve ; Sensitivity and Specificity ; Sepsis ; diagnosis ; physiopathology ; Serum Amyloid P-Component ; analysis ; Troponin ; blood
6.Clinical significance of PCT, CRP, ESR, WBC count as predictors in postoperative early infectious complications with fever after posterior lumbar internal fixation.
Le WANG ; Bo YANG ; Biao YIN ; Zhi ZHANG ; Liang ZHANG ; Long TANG ; Ai-ju LOU
China Journal of Orthopaedics and Traumatology 2015;28(1):66-70
OBJECTIVETo evaluate the role of serum level of procalcitonin (PCT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WBC) as predictors in postoperative early infectious complications with fever after posterior lumbar internal fixation (PLIF).
METHODSA retrospective study was conducted from January 2012 to January 2014. Fifty-two patients with fever in the early stage(within 10 days) after the PLIF were collected in the study. They were divided into infection group and non-infection group (group A and group B) according to the results of postoperative blood culture. There were 26 patients in group A and 32 patients in group B. The values of PCT, CRP, ESR, and WBC count were compared and analyzed between two groups.
RESULTSThe values of PCT, CRP, and ESR in group A were higher than those of group B. Meanwhile, CRP and ESR in group B were still higher than the normal range. Among the 26 patients with infections (group A), PCT was superior to CRP and ESR, had a good ability in discriminating different kinds of postoperative infections. The area under the ROC curve of serum PCT levels was the largest (CI 95% was 0.81 to 0.98) in the indexs; and ROC curve of WBC count was no statistically significant. When the cut off points of each predictors were evaluated, the higher sensitive was CRP and reached at 90.27% and the higher specific was ESR and reached at 88.50%.
CONCLUSIONFor the patients with fever at the early stage after the PLIF should be paid attention and reasonable choosing predictors are helpful to identify postoperative infection in the early stage. The CRP and ESR may be influenced by the surgery, and the PCT level is helpful to differentiate infection type.
Adult ; Aged ; Aged, 80 and over ; Blood Sedimentation ; C-Reactive Protein ; analysis ; Calcitonin ; blood ; Calcitonin Gene-Related Peptide ; Female ; Fever ; blood ; diagnosis ; Fracture Fixation, Internal ; adverse effects ; Humans ; Infection ; blood ; diagnosis ; Leukocyte Count ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Postoperative Complications ; blood ; diagnosis ; Protein Precursors ; blood
7.The significance of monitoring procalcitonin when applying antibiotics to trichlorethylene dermatitis.
Jie SITU ; Xueqin YANG ; Chunmei LIN ; Shiliang WEI ; Liu SHI ; Ningyu ZHANG ; Lingli LUO ; Jianjie ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2015;33(3):218-220
OBJECTIVETo investigate the significance of monitoring procalcitonin (PCT) when applying antibiotics to trichlorethylene (TCE)-induced dermatitis.
METHODSOne hundred and two patients who were hospitalized and recovered from TCE-induced dermatitis in our hospital from 2006 to 2013 were enrolled as subjects. Based on whether the PCT level was monitored or not, we divided patients into regular group and PCT group. For the regular group, we applied antibiotic treatment and determined the course of treatment based on clinical symptoms, laboratory test results, medical imaging results, and bacterial culture. For the PCT group, in addition to the above treatments, antibiotic treatment was applied when the PCT level was not lower than 0.25 ng/ml and stopped when the PCT level was lower than 0.25 ng/ml. The distribution of bacterial infection sites, type of bacteria, type of antibiotics, average period of hospitalization, and course of antibiotic treatment were compared between the two groups.
RESULTSThere were no significant differences in the distribution of bacterial infection sites, type of bacteria, type of antibiotics, and average period of hospitalization between the two groups (P > 0.05). The course of antibiotic treatment for the PCT group was significantly shorter than that for the regular group (25.37 ± 11.66 vs 20.58 ± 7.53 d, P < 0.05).
CONCLUSIONUnder similar conditions of bacterial infection, antibiotic treatment of TCE-induced dermatitis based on the serum PCT level can significantly shorten the course of treatment and avoid the abuse of antibiotics.
Anti-Bacterial Agents ; therapeutic use ; Bacteria ; Bacterial Infections ; Calcitonin ; analysis ; Calcitonin Gene-Related Peptide ; Drug Eruptions ; drug therapy ; Hospitalization ; Humans ; Monitoring, Physiologic ; Protein Precursors ; analysis ; Trichloroethylene ; toxicity
8.The Influence of Alcoholic Liver Disease on Serum PIVKA-II Levels in Patients without Hepatocellular Carcinoma.
Keunhee KANG ; Ji Hoon KIM ; Seong Hee KANG ; Beom Jae LEE ; Yeon Seok SEO ; Hyung Joon YIM ; Jong Eun YEON ; Jong Jae PARK ; Jae Seon KIM ; Young Tae BAK ; Kwan Soo BYUN
Gut and Liver 2015;9(2):224-230
BACKGROUND/AIMS: Prothrombin induced by vitamin K deficiency or antagonist II (PIVKA-II) is a widely used diagnostic marker for hepatocellular carcinoma (HCC). We evaluated the correlation between alcoholic liver disease (ALD) and serum PIVKA-II levels in chronic liver disease (CLD) patients. METHODS: We retrospectively reviewed the medical records of 2,528 CLD patients without HCC. Among these patients, 76 exhibited serum high PIVKA-II levels of >125 mAU/mL (group 1). We categorized 76 control patients matched by age, sex, and the presence of liver cirrhosis from the remaining patients who were negative for serum PIVKA-II (group 2). RESULTS: Group 1 revealed increased antibiotic usage (23.7% vs 2.6%, p<0.001) and incidence of ALD (60.5% vs 14.5%, p<0.001) as well as elevated aspartate aminotransferase (52.5 IU/L vs 30.5 IU/L, p=0.025) and gamma glutamyl transpeptidase (67.5 IU/L vs 36.5 IU/L, p=0.005) levels compared with group 2. Further, group 1 was significantly associated with a worse Child-Pugh class than group 2. In the multivariate analysis, ALD (odds ratio [OR], 7.151; p<0.001) and antibiotic usage (OR, 5.846; p<0.001) were significantly associated with positive PIVKA-II levels. CONCLUSIONS: Our study suggests that ALD and antibiotics usage may be confounding factors when interpreting high serum PIVKA-II levels in patients without HCC. Therefore, serum PIVKA-II levels in patients with ALD or in patients administered antibiotics should be interpreted with caution.
Adult
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Age Distribution
;
Aged
;
Anti-Bacterial Agents/therapeutic use
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Aspartate Aminotransferases/blood
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Biomarkers/*blood
;
Carcinoma, Hepatocellular/blood
;
Diagnosis, Differential
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Female
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Humans
;
Liver Cirrhosis/blood
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Liver Diseases, Alcoholic/*blood
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Liver Neoplasms/blood
;
Male
;
Matched-Pair Analysis
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Middle Aged
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Multivariate Analysis
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Protein Precursors/*blood
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Prothrombin/analysis
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Retrospective Studies
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Sex Distribution
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gamma-Glutamyltransferase/blood
9.The Influence of Alcoholic Liver Disease on Serum PIVKA-II Levels in Patients without Hepatocellular Carcinoma.
Keunhee KANG ; Ji Hoon KIM ; Seong Hee KANG ; Beom Jae LEE ; Yeon Seok SEO ; Hyung Joon YIM ; Jong Eun YEON ; Jong Jae PARK ; Jae Seon KIM ; Young Tae BAK ; Kwan Soo BYUN
Gut and Liver 2015;9(2):224-230
BACKGROUND/AIMS: Prothrombin induced by vitamin K deficiency or antagonist II (PIVKA-II) is a widely used diagnostic marker for hepatocellular carcinoma (HCC). We evaluated the correlation between alcoholic liver disease (ALD) and serum PIVKA-II levels in chronic liver disease (CLD) patients. METHODS: We retrospectively reviewed the medical records of 2,528 CLD patients without HCC. Among these patients, 76 exhibited serum high PIVKA-II levels of >125 mAU/mL (group 1). We categorized 76 control patients matched by age, sex, and the presence of liver cirrhosis from the remaining patients who were negative for serum PIVKA-II (group 2). RESULTS: Group 1 revealed increased antibiotic usage (23.7% vs 2.6%, p<0.001) and incidence of ALD (60.5% vs 14.5%, p<0.001) as well as elevated aspartate aminotransferase (52.5 IU/L vs 30.5 IU/L, p=0.025) and gamma glutamyl transpeptidase (67.5 IU/L vs 36.5 IU/L, p=0.005) levels compared with group 2. Further, group 1 was significantly associated with a worse Child-Pugh class than group 2. In the multivariate analysis, ALD (odds ratio [OR], 7.151; p<0.001) and antibiotic usage (OR, 5.846; p<0.001) were significantly associated with positive PIVKA-II levels. CONCLUSIONS: Our study suggests that ALD and antibiotics usage may be confounding factors when interpreting high serum PIVKA-II levels in patients without HCC. Therefore, serum PIVKA-II levels in patients with ALD or in patients administered antibiotics should be interpreted with caution.
Adult
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Age Distribution
;
Aged
;
Anti-Bacterial Agents/therapeutic use
;
Aspartate Aminotransferases/blood
;
Biomarkers/*blood
;
Carcinoma, Hepatocellular/blood
;
Diagnosis, Differential
;
Female
;
Humans
;
Liver Cirrhosis/blood
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Liver Diseases, Alcoholic/*blood
;
Liver Neoplasms/blood
;
Male
;
Matched-Pair Analysis
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Middle Aged
;
Multivariate Analysis
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Protein Precursors/*blood
;
Prothrombin/analysis
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Retrospective Studies
;
Sex Distribution
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gamma-Glutamyltransferase/blood
10.Serum Dickkopf-1 as a Biomarker for the Diagnosis of Hepatocellular Carcinoma.
Seung Up KIM ; Jeon Han PARK ; Hyon Suk KIM ; Jae Myun LEE ; Hyun Gyu LEE ; Hyemi KIM ; Sung Hoon CHOI ; Shinhwa BAEK ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Jong Doo LEE ; Kwang Hyub HAN
Yonsei Medical Journal 2015;56(5):1296-1306
PURPOSE: Dickkopf-1 (DKK-1) is a Wnt/beta-catenin signaling pathway inhibitor. We investigated whether DKK-1 is related to progression in hepatocellular carcinoma (HCC) cells and HCC patients. MATERIALS AND METHODS: In vitro reverse-transcription polymerase chain reaction (RT-PCR), wound healing assays, invasion assays, and ELISAs of patient serum samples were employed. The diagnostic accuracy of the serum DKK-1 ELISA was assessed using receiver operating characteristic (ROC) curves and area under ROC (AUC) analyses. RESULTS: RT-PCR showed high DKK-1 expression in Hep3B and low in 293 cells. Similarly, the secreted DKK-1 concentration in the culture media was high in Hep3B and low in 293 cells. Wound healing and invasion assays using 293, Huh7, and Hep3B cells showed that DKK-1 overexpression promoted cell migration and invasion, whereas DKK-1 knock-down inhibited them. When serum DKK-1 levels were assessed in 370 participants (217 with HCC and 153 without), it was significantly higher in HCC patients than in control groups (median 1.48 ng/mL vs. 0.90 ng/mL, p<0.001). The optimum DKK-1 cutoff level was 1.01 ng/mL (AUC=0.829; sensitivity 90.7%; specificity 62.0%). Although DKK-1 had a higher AUC than alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) (AUC=0.829 vs. 0.794 and 0.815, respectively), they were statistically similar (all p>0.05). When three biomarkers were combined (DKK-1 plus AFP plus DCP), they showed significantly higher AUC (AUC=0.952) than single marker, DKK-1 plus AFP, or DKK-1 plus DCP (all p<0.001). CONCLUSION: DKK-1 might be a key regulator in HCC progression and a potential therapeutic target in HCC. Serum DKK-1 could complement the diagnostic accuracy of AFP and DCP.
Area Under Curve
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Biomarkers/blood/metabolism
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Biomarkers, Tumor/blood
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Carcinoma, Hepatocellular/blood/*diagnosis
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Enzyme-Linked Immunosorbent Assay
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Female
;
Humans
;
Intercellular Signaling Peptides and Proteins/*blood/*metabolism
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Liver Neoplasms/blood/*diagnosis
;
Male
;
Middle Aged
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Protein Precursors/blood/metabolism
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Prothrombin/metabolism
;
ROC Curve
;
Reverse Transcriptase Polymerase Chain Reaction/*methods
;
Sensitivity and Specificity
;
alpha-Fetoproteins/analysis/metabolism

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