title: Increased levels of β-catenin, LEF-1, and HPA-1 correlate with poor prognosis for acral melanoma with negative BRAF and NRAS mutation in BRAF exons 11 and 15 and NRAS exons 1 and 2.
abstract: To determine the expression of β-catenin, lymphoid enhancer-binding protein-1 (LEF-1), and heparanase-1 (HPA-1) and to evaluate these proteins' potential prognostic values in malignant acral melanoma without mutations in BRAF exons 11 and 15 and NRAS exons 1 and 2, specimens from 90 patients with wild-type BRAF and NRAS were assessed and analyzed by immunohistochemistry and western blotting. The positive expression of β-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was observed in 36 (72%), 31 (62%), and 32 (64%) of the detected acral melanomas, respectively. The expression of β-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was not correlated with gender, age, or diseased body parts (p>0.05), but was significantly positively correlated with the tumor node metastasis (TNM) stage and metastasis (correlation=0.406 and 0.716, 0.397 and 0.582, 0.353 and 0.579; p=0.040 and 0.0001, 0.0040 and 0.0001, 0.0120 and 0.0001, respectively). We also observed that the increased expression of β-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was significantly correlated with decreased survival and poor prognosis (p=0.001, 0.010, and 0.023, respectively). A multifactorial analysis using Cox's regression model revealed that β-catenin, lymphoid enhancer-binding protein-1, heparanase-1, and the TNM stage were all independent factors in malignant melanoma (risk ratios were 7.294, 5.550, 5.622, and 4.794; p-values were 0.007, 0.018, 0.018, and 0.029, respectively). This study may provide the basis for the use of β-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 as novel targets in the treatment of malignant invasion and metastasis in acral melanoma cancer. The expression of β-catenin, LEF-1, and HPA-1 was assessed and compared in malignant melanoma with that of peritumoral tissue and benign nevus in the patients with negative mutations in BRAF exons 11 and 15 and NRAS exons 1 and 2. The study may provide the basis for β-catenin, LEF-1, and HPA-1 as new targets in the treatment of malignant invasion and metastasis in melanoma cancer.
authors.affiliation: 1 Department of Orthopedics, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province , Kunming, People's Republic of China .
authors.forename: Sanxiong
authors.initials: S
authors.lastname: Xu
authors.forename: Zuozhang
authors.initials: Z
authors.lastname: Yang
authors.forename: Jinyu
authors.initials: J
authors.lastname: Zhang
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Chen
authors.forename: Hongjun
authors.initials: H
authors.lastname: Li
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Liu
authors.forename: Da
authors.initials: D
authors.lastname: Xu
authors.forename: Yanjin
authors.initials: Y
authors.lastname: Chen
authors.forename: Yihao
authors.initials: Y
authors.lastname: Yang
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dongxu
authors.initials: D
authors.lastname: Li
authors.forename: Junfeng
authors.initials: J
authors.lastname: Xia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012306:Risk; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism*; D000099175:Heparanase
chemical_list: D020558:GTP Phosphohydrolases; D005966:Glucuronidase; D051821:Lymphoid Enhancer-Binding Factor 1; D008565:Membrane Proteins; D048493:Proto-Oncogene Proteins B-raf; D051176:beta Catenin; D000099175:Heparanase; C495270:CTNNB1 protein, human; C497573:LEF1 protein, human; C482119:BRAF protein, human; C579846:NRAS protein, human