This study investigates the biokinetics of LGT proteome, a potential biomarker of severe TBI, in serum of severe TBI patients. The LGT proteome presents in the serum of severe TBI patients. The abundance diversity of LGT proteome is closely associated with pathologic condition of TBI patients. Serum LGT proteome may be used as a promising marker for evaluating severity of severe TBI.
Traumatic brain injury (craniocerebral injury, TBI) is the most common disease with high morbidity and mortality in neurosurgery, especially to the youngsters, and a lot of researchers have focused on this fact [
Serum protein biomarkers have long held promise in the study of TBI. They are considered to facilitate the diagnosis, monitoring progress, prognosis, and providing pertinent molecular information about ongoing pathological changes for designing evidence-based therapeutic interventions [
Based on the findings above, LGT can also be found in severe TBI patients’ serum, and it may be the early warning sign for disease aggravation or even death. In order to investigate the clinical significance of LGT proteome, the study proceeded with surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) [
96 TBI cases treated in our department between March 2006 and July 2009 were analyzed retrospectively. There were 77 males and 19 females with age range of 16–83 years (mean age:
The main instruments and reagents included protein fingerprint meter, WCX2 chips, PBS-IIc chip reading machine, and Ciphergen ProteinChip 3.2 analysis software, urea, sodium acetate [NaAc (100 mmol/L NaAc pH 4.0)], HPLC water, and SPA.
5 mL sera were taken in the morning when patients were hollow and were put in VACVTTE vacuum quantitative mining container and placed at room temperature for 60 min (including the time when samples were out of the body), and then the serum was separated from blood at 3000 g × 10 min and preserved at −80°C; serum samples were thawed and put in ice bath (10000 g × 2 min); take 5
Chip was put into the container with hydrochloric acid (100 mmol/L), oscillated for 4~5 min, and then washed with HPLC water; put the chip into the bioprocessor: start with each hole plus 200
The same parameters were used for all the samples; data were collected using Ciphergen ProteinChip 3.2 analysis software. Set inspection sample laser intensity at 195, detection sensitivity at 8, collected data quality load ratios (
In the fingerprint, qualitative load ratios (
All measurement data was represented with mean ± standard deviation (
The expression of LGT proteome was
LGT proteome does not present in the protein fingerprint spectra of normal controls.
LGT proteome presents in protein fingerprint spectra of TBI group.
On the first day within 24 hours of admission, we collected the first serum specimen to detect the differences of TBI patients’ LGT proteome abundance values. The result shows that the LGT proteome abundance of the GCS 6–8 severe TBI group and GCS 3–5 severe TBI group was obviously higher than of the control group; the LGT proteome abundance of the GCS 3–5 severe TBI group was significantly higher than of the GCS 6–8 severe TBI group (Table
The LGT proteome abundance comparison in the GCS 6–8 severe TBI group, GCS 3–5 severe TBI group, and normal controls.
Group | Cases ( |
Positive proportion | Positive rate (%) | LGT proteome abundance (%) |
---|---|---|---|---|
GCS 3–5 severe TBI group | 44 | 37/44 | 84.09 |
17.37 ± 6.87 |
GCS 6–8 severe TBI group | 52 | 21/52 | 38.46 | 8.39 ± 5.38 |
Normal controls | 35 | 0/35 | 0 | 1.79 ± 0.81 |
According to the different types of TBI, all the cases were assigned into ① brain stem injury and diffuse axonal injury, ② contusion and laceration of brain and (or) subdural/intracerebral hematoma, and ③ epidural hematoma and/or skull fractures, analyzing three groups of LGT proteome abundance values. Results showed that the LGT proteome abundance values of groups ① and ② were significantly higher than of group ③, and the difference was statistically significant (
The analysis of the LGT proteome abundance in different TBI groups.
Group | Cases ( |
LGT proteome abundance |
---|---|---|
①: brain stem injury and diffuse axonal injury | 35 | 15.68 ± 10.73 |
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②: contusion and laceration of brain and (or) subdural/intracerebral hematoma | 47 | 14.16 ± 9.89 |
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③: epidural hematoma and (or) skull fracture | 14 | 5.97 ± 5.13 |
LGT proteome expression was detected in two groups of patients in the whole procedure; death group was higher than the survival group in the course of different stages; then, the abundance values of two groups showed a gradual decline rather than a progressive manner. Besides, a moderate elevation was shown in both groups on the seventh day. During the early phase (days 1 and 4), LGT proteome abundance value of death group was significantly higher than of the survival group (
The Comparison of LGT proteome abundance in different pathogenetic stage.
Prognosis | Day 1 | Day 4 | Day 7 | Day 14 | |
---|---|---|---|---|---|
Death group | Cases |
29 |
23 |
16 |
9 |
|
|||||
Survival group | Cases |
67 |
67 |
67 |
67 |
|
|||||
|
<0.01 | <0.05 | >0.05 | >0.05 |
Traumatic brain injury (TBI) is the leading cause of death and disability among young adults [
Recently, Pei et al. [
Identification and purification of candidate biomarkers is a critical step in the biomarker development process, since it provides insight into the disease biology and facilitates the development of analyte-specific assays [
The experiment proceeded through SELDI-TOF-MS technology; the LGT proteome was detected in the proteome fingerprint with 100% relative abundance. A fingerprint marker just like a cluster appeared between 11100 Da and 11900 Da
Our present study divided the TBI patients into three groups: ① brain stem injury and diffuse axonal injury, ② contusion and laceration of brain and (or) subdural/intracerebral hematoma, and ③ epidural hematoma and (or) skull fracture. The result showed that the LGT proteome abundance in groups ① and ② was significantly higher than in group ③ (
The experiment also analyzed the LGT proteome abundance during the dynamic change of severe TBI patients. The LGT proteome abundance was higher in death group than in survival group in the initial pathologic stage and then decreased in the two groups as the course was prolonged. At the early pathologic stage (days 1 and 4), the LGT proteome abundance was significantly higher in death group than in survival group (
This is the first study to investigate the biokinetics of LGT proteome, a potential biomarker of severe TBI, in serum of severe TBI patients. The LGT proteome presents in the serum of severe TBI patients. The abundance diversity of LGT proteome is closely associated with pathologic condition of TBI patients. Serum LGT proteome may be used as a promising marker for evaluating severity of severe TBI. Further studies of LGT proteome are needed to validate these findings in a larger scale of samples and should be conducted to support these associations with outcomes.
Serum LGT proteome was detected by surface enhanced laser desorption/ionisation time-of-flight mass spectrometer (SELDI-TOF-MS). The LGT proteome presents in the serum of severe TBI patients. The abundance diversity of LGT proteome is intimately associated with pathogenetic condition of TBI patients. Serum LGT proteome may be used as a promising marker for evaluating severity of severe TBI.
The topics presented herein are not covered by any manufacturer and the relevant employer or other economic organizations or direct or indirect economic interests of sponsors.
Hongming Ji and Changchen Hu contributed equally to this work and should be considered co-first authors.
This research was funded by Medical Science and Technology Research projects of Health Department of Hubei Province (JX4B42) and by the National Science Foundation of China (30901774) and National Science Foundation of Shanxi (2014011038-2).