뇌종양 환자에서 성장인자 granulin 발현과 예후와의 관계

Abstract

Background: Granulin is cysteine-rich polypeptides belonging to a family of growth factors that mediate cell cycle progression and cell motility. Granulin is expressed in several types of human brain tumors including gliomas and meningiomas; however, its clinical significance in terms of patient outcomes has not been verified. Purpose: To investigate the relationships between granulin expression, clinical data, and patient prognosis in intracranial brain tumors. Material and Methods: Tumor tissues were obtained from 295 patients whose brain tumors were surgically treated, and the expression of granulin was assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Clinical characteristics comprising demographic data and radiologic findings were obtained to analyze clinical outcomes. In addition, author classified pathologically brain tumors according to World Health Organization (WHO) classifications into non-aggressive (WHO grades I and II) or aggressive (WHO grades III, IV and metastatic) tumors and evaluated the prognostic implications of granulin expression between the two groups. Result: Among all 295 tumor specimens, 107 exhibited positive expression of granulin. Further, 57 (28.3%) of the 201 patients in the non-aggressive group and 50 (53.1%) of 94 patients in the aggressive group had granulin-positive tumors. Granulin expression did not vary according to the various demographic data collected (p > 0.05). In the non-aggressive tumor group, the mortality and recurrence rates were 6.2% and 8.3% in the granulin-negative group and 9.5% and 11.4% in the granulin-positive group, respectively. In the aggressive tumor group, the mortality and recurrence rates were 18.2% and 45.5% in the granulin-negative group and 30.0% and 70.0% in the granulin-positive group, respectively. For both groups, the mortality rate was significantly different between patients with granulin-positive and granulin-negative tumors (p < 0.05). Kaplan-Meier survival analysis showed that the survival rates of patients with granulin-positive tumors was lower than that of patients with granulin-negative tumors (p = 0.028 by Log-rank test), and that the rate of recurrence was higher in patients with granulin-positive tumors compared to those with granulin-negative tumors (p = 0.026 by Log-rank test). Conclusions: This study suggests that granulin is expressed in various brain tumors, and that its expression is correlated with the prognosis of patients with brain tumors. These results suggest that granulin may be a novel target for management of intracranial tumors.