Expression of CLIC1 and IGFBP7 in Complete Hydatidiform Mole

XIAO Ping, YIN Ru-tie, XIE Dan. et al

Abstract

To investigate the expression level of chloride intracellular channel 1 (CLIC1) and insulin-like growth factor binding protein 7 (IGFBP7) in complete hydatidiform mole (CHM) and estimate the relationship between the expression level and clinical prognosis. Methods Immunohistochemistry (IHC) method was used to detect the expression level of P57KIP2 in order to differentiate CHM. CLIC1 and IGFBP7 expression level of CHM were measured by IHC method then. Results ① According to the P57KIP2 expression result 66 patients were diagnosed as CHM (85.71%). Fourteen of 66 patients progressed into gestational trophoblastic neoplasia (GTN), which accounted for 21.21%. ② The results of IHC showed that CLIC1 significantly higher expressed in malignant group than spontaneous regressive group (P=0.014). IGFBP7 significantly down-regulated in malignant group (P=0.002). ③ Pearson correlation analysis results revealed that there were no relation between the expression of CLIC1 and IGFBP7 (P=0.761). Logistic regression analysis indicated that down-regulation of IGFBP7 was the independent risk factors of CHM progression, P=0.005, OR=8.493 〔95% confidence interval (CI): 1.878-38.401〕; Serum hCG>5×105 mIU/mL was the independent risk factors of CHM progression too, P=0.011, OR=11.251 (95% CI: 1.731-73.151). ④ Receiver operator characteristic curve (ROC curve) results showed that the area under the curve (AUC) of CLIC1 was 0.707. The optimum cut off was 10.5, and correspondingly sensitivity was 42.90%, specificity 94.20%. AUC of IGFBP7 was 0.764. The optimum cut off was 7.0, and the correspondingly sensitivity and specificity were 64.30% and 78.80% respectively. Combining the two markers in series, the sensitivity of predicting the prognosis of CHM was 21.42%, while the specificity was 100%. When combining in parallel, the sensitivity and specificity were 85.71% and 71.15% respectively. Conclusion Up-regulation of CLIC1 and down-regulation of IGFBP7 might pay an important role in progression of CHM, but there was no relationship between the expression levels of them. The predictive values of malignance transformation of CHM with the two biomarkers were with certain accuracy, and combining them in parallel test could improve accuracy. They are promising to be candidate prognostic markers of CHM.

 

Keywords: Complete hydatidiform mole, Chloride intracellular channel 1 Insulin-like growth factor binding protein 7, Prognosis 

 

Full Text:

PDF


References


Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol,2010;203(6):531-539.

Kim DS. Moon H. Kim KT. Effects of prophylactic chemotherapy for persistent trophoblastic disease in patients with complete hydatidiform mole. Obstet Gynecol, 1986; 67 (4): 690-694.

Kashimura Y, Kashimura M, Sugimori H. et al. Prophylactic chemotherapy for hydatidiform moles. Five to 15 years follow up. Cancer, 1986;58(3):624-629.

Rahman A, Kumar SG, KimSW. Et al. Proteomic analysis for inhibitory effect of chitosan oligosaccharides on 313-LI adipocyte differentiation. Proteomics,2008;8(3);569-581.

Wang JW, Peng SY, Li JT, et al. Identification of metastasis- associated proteins involved in gallbladder carcinoma metastasis by proteomic analysis and functional exploration of chloride intracellular channel 1. Cancer Lett,2009;281( 1) ;71-81.

Murphy M, Pykett MJ, Harnish P. et al. Identification and characterization of genes differentially expressed in meningiomas. Cell Growth Differ, 1993;4С9):715-722.

Sprenger CC, Damon SE. Insulin-like growth factor binding protein-related protein 1 ( IGFBP-rPl ) is a potential tumor suppressor protein for prostate cancer. Cancer Res, 1999; 59 (10):2370-2375.

Kipp BR, Ketterling RP, Oberg TN, et al. Comparison of fluorescence in situ hybridization, p57 immunostaining, flow cytometry, and digital image analysis for diagnosing molar and nonmolar products of conception. Am J Clin Pathol. 2010; 133 (2): 196-204.

An W, Ben QW, Chen HT. elal. Low expression of IGFBP7 is associated with poor outcome of pancreatic ductal adenocarcinoma. Ann Surg Oncol,2012; 19(12) ;3971-3978.

Fisher RA, Hodges MD, Rees НС, et al. The maternally transcribed gene p57 ( K1P2 ) ( CDNK1C) is abnormally expressed in both androgenetic and biparental complete hydatidiform moles. Hum Mol Genet, 2002; 11 ( 26 ): 3267- 3272.

Kihara M, Matsui H. Seki K. et al. Genetic origin and imprinting in hydatidiform moles. Comparison between DNA polymorphism analysis and immunoreactivity of p57KJ>L> J Reprod Med,2005;50(5):307-312.

Sarmadi S, Izadi-Mood N, Abbasi A, et al. p57K,1>2 immunohistochemical expression; a useful diagnostic tool in discrimination between complete hydatidiform mole and its mimics. Arch Gynecol Obstet,2011;283(4):743-748.

Huang JS, Chao CC, Su TL, et al. Diverse cellular transformation capability of overexpressed genes in human hepatocellular carcinoma. Biochem Biophys Res Commun. 2004;315(4):950-958.

Petrova DT, Asif AR, Armstrong VW, et al. Expression of chloride intracellular channel protein 1 (CLIC1 ) and tumor protein D52 (TPD52) as potential biomarkers for colorectal cancer. Clin Biochem,2008;41 ( 14-15): 1224-1236.

WangJW, Peng SY, Li JT, et al. Identification of metastasis- associated proteins involved in gallbladder carcinoma metastasis by proteomic analysis and functional exploration of chloride intracellular channel 1. Cancer Lett,2009;281(1) :71-81.

Chen CD. Wang CS, Huang YH, et al. Overexpression of CLIC1 in human gastric carcinoma and its clinicopathological significance. Proteomics, 2007 ; 7(1); 155-167.

Shi ZH, Zhao C, Wu H, et al. CLICl protein; a candidate prognostic biomarker for malignant-transformed hydatidiform moles. Int J Gyne col Cancer,2011;21 (1): 153-160.

Pen A, Durocher Y, Slinn J, et al. Insulin-like growth factor binding protein 7 exhibits tumor suppressive and vessel stabilization properties in U87MG and T98G glioblastoma cell lines. Cancer Biol Ther,2011; 12(7);634-646.

Chen D, Yoo BK, Santhekadur PK, et al. Insulin-like growth factor-binding protein-7 functions as a potential tumor suppressor in hepatocellular carcinoma. Clin Cancer Res,2011; 17(21);6693-6701.

Chen Г), Siddiq A, Emdad L. et al. Insulin-like growth factor- binding protein-7 (IGFBP7): a promising gene therapeutic for hepatocellular carcinoma (HCC). Mol Ther,2013;21(4); 758- 766.

Benatar T, Yang W. Amemiya Y. et al. IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways. Breast Cancer Res Treat ,2012; 133(2):563-573.

Sepiashvili L. Hui A, Ignatchenko V, et al. Potentially novel candidate biomarkers for head and neck squamous cell carcinoma identified using an integrated cell line-based discovery strategy. Mol Cell Proteomics, 2012; 11 ( 11 ): 1404- MIS.

Liu ZKt Liu HY. Fang WN. et al. Insulin-like growth factor binding protein 7 modulates estrogen-induced trophoblast proliferation and invasion in HTR-8 and JEG-3 cells. Cell Biochem Biophys,2012;63(1):73-84.


Refbacks

  • There are currently no refbacks.