LAPTM4B-35 overexpression is a risk factor for tumor recurrence and poor prognosis in hepatocellular carcinoma.
OBJECTIVE
Lysosomal protein transmembrane 4 beta-35 (LAPTM4B-35) is a tetra-transmembrane glycoprotein that is abundantly localized on membrane-bound organelles including endosomes and lysosomes, and promotes cell proliferation and tumorigenesis through regulation of cell cycle and signaling pathways. The aim of the present study is to determine the potential clinical implications of LAPTM4B-35 expression in hepatocellular carcinoma (HCC).


METHODS
Immunohistochemistry assay was used to determine the expression of LAPTM4B-35 protein in normal and HCC tissues from 71 patients. The correlations of LAPTM4B-35 expression with clinicopathological parameters, including gender, age, background liver, viral status, tumor size, portal vein invasion, histopathological differentiation, serum AFP level, TNM staging and recurrence of HCC were assessed by Chi-squared test. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. Cox regression (Proportional hazard model) was adopted for multivariate analysis of prognostic factors.


RESULTS
LAPTM4B-35 immunoreactivity was negative or low in normal liver tissues, but high in HCC tissues (51/71, 71.8%). The overexpression of LAPTM4B-35 was significantly associated with recurrence, TNM staging and portal vein invasion of HCC. Patients with high LAPTM4B-35 expression had significantly poorer overall survival (OS) and disease-free survival (DFS) (both P < 0.001) when compared with patients with the low expression of LAPTM4B-35. On multivariate analysis, LAPTM4B-35 expression was found to be an independent prognostic factor for OS and DFS (P = 0.018 and P = 0.001, respectively).


CONCLUSIONS
LAPTM4B-35 expression showed a strong association with the potencies of recurrence and metastasis and progression of HCC, and that may be applied as a novel marker for the prediction of recurrence and metastasis potency of HCC, and helpful for improving the diagnosis, prognosis and treatment of HCC.
Yang
Hua
H
Department of Cell Biology, School of Basic Medical Sciences, Peking University, 100191, Beijing, China.
Xiong
Fu Xia
FX
Lin
Ming
M
Yang
Yu
Y
Nie
Xiu
X
Zhou
Rou Li
RL
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D009367:Neoplasm Staging; D015513:Oncogene Proteins / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C477083:LAPTM4B protein, human; D008565:Membrane Proteins; D015513:Oncogene Proteins
Beijing Da Xue Xue Bao Yi Xue Ban. 2003 Aug;35(4):348-52
12947546
Am J Surg. 2009 Jul;198(1):39-45
19178896
Beijing Da Xue Xue Bao Yi Xue Ban. 2003 Aug;35(4):340-7
12947545
Semin Liver Dis. 2004 Feb;24(1):77-88
15085488
Ann Surg Oncol. 2009 Jun;16(6):1560-71
19259739
Cancer Res. 1999 Oct 1;59(19):4890-7
10519401
Nat Rev Cancer. 2006 Sep;6(9):674-87
16929323
Oncol Rep. 2008 Nov;20(5):1077-83
18949404
Cancer. 2005 Jan 15;103(2):307-12
15593087
J Cancer Res Clin Oncol. 2008 Jun;134(6):705-14
18084776
Clin Liver Dis. 2005 May;9(2):191-211, v
15831268
Am J Surg Pathol. 2007 May;31(5):681-9
17460450
Exp Cell Res. 1999 Nov 25;253(1):210-29
10579924
J Am Coll Surg. 2009 Mar;208(3):368-74
19317998
Oncogene. 2003 Aug 7;22(32):5060-9
12902989
J Biol Chem. 1999 Apr 30;274(18):12877-82
10212276
World J Gastroenterol. 2004 Jun 1;10(11):1555-9
15162524
Hepatology. 1999 Aug;30(2):408-12
10421648
Science. 1991 Oct 11;254(5029):274-7
1833819
Genes Dev. 1999 Nov 15;13(22):2905-27
10579998
Lancet. 2003 Dec 6;362(9399):1907-17
14667750